GIT- Bio Chem

• The oxidative phase of the HMP shunt (Pentose Phosphate Pathway) generates:

  • NADPH (used for fatty acid synthesis, cholesterol synthesis, detoxification, and maintaining reduced glutathione in RBCs).

  • Ribulose-5-phosphate (precursor for nucleotide synthesis in the non-oxidative phase).

• This NADPH production is crucial for:

  • Anabolic reactions (e.g., fatty acid, steroid synthesis).

  • Antioxidant defense (via glutathione reduction).

  • Respiratory burst in neutrophils.

Why the other options are wrong

• NADH ❌ → Produced in glycolysis, TCA cycle, and β-oxidation (used in oxidative phosphorylation).

• ATP ❌ → Generated in glycolysis and oxidative phosphorylation, not in the HMP shunt.

• O₂ ❌ → Not a direct product of this pathway.

• Glucose ❌ → Substrate for glycolysis/HMP shunt, not a product.

UDP-glucuronosyltransferase (UGT) is the key enzyme in the process of glucuronidation, a phase II biotransformation reaction. It catalyzes the transfer of glucuronic acid from UDP-glucuronic acid to substrates (like bilirubin, drugs, hormones, toxins), making them more water-soluble for excretion in bile or urine.

• UGT is an ER-membrane–bound enzyme (specifically, in the smooth endoplasmic reticulum).

• That’s why hepatocytes with well-developed SER are the primary site for detoxification reactions.

Why the Other Options Are Wrong

Golgi apparatus ❌

• The Golgi modifies, sorts, and packages proteins and lipids.

• It is not the main site for glucuronidation.

Mitochondria ❌

• Mitochondria handle oxidative phosphorylation, TCA cycle, fatty acid oxidation.

• They do not play a role in glucuronidation.

Cytosol ❌

• Some phase II enzymes (e.g., glutathione-S-transferase) are cytosolic, but UGT is specifically ER-bound, not cytosolic.

Nucleolus ❌

• The nucleolus is involved in ribosomal RNA synthesis and ribosome assembly.

• No detoxification enzymes are located here.

• FMN (Flavin mononucleotide) is a coenzyme derived from riboflavin (vitamin B2).

• In the body, riboflavin is phosphorylated by riboflavin kinase to form FMN.

• FMN can be further converted to FAD (flavin adenine dinucleotide) by addition of AMP.

• Both FMN and FAD serve as important cofactors in oxidation–reduction reactions (e.g., in complex I and II of the electron transport chain).

Why the other options are incorrect

Vitamin B12 (Cobalamin) ❌

• Functions in methyl group transfers and odd-chain fatty acid metabolism, not FMN formation.

Thiamine (Vitamin B1) ❌

• Forms thiamine pyrophosphate (TPP), a coenzyme in decarboxylation reactions, not FMN.

Pyridoxine (Vitamin B6) ❌

• Forms pyridoxal phosphate (PLP), a coenzyme for transamination and amino acid metabolism, not FMN.

Niacin (Vitamin B3) ❌

• Forms NAD⁺ and NADP⁺, coenzymes in redox reactions, not FMN.

• The electron transport chain (ETC) occurs in the inner mitochondrial membrane.

• Electrons move sequentially through complexes I–IV, ultimately reducing oxygen to water.

• The final step occurs in Complex IV (cytochrome c oxidase), which contains cytochromes a and a3 along with copper ions.

• Here, electrons are transferred from cytochrome c → cytochrome a → cytochrome a3 → oxygen.

• Oxygen is the final electron acceptor, combining with electrons and protons to form H₂O.

Why the other options are incorrect

NAD ❌

• NADH donates electrons to Complex I, but it is not directly involved in reducing oxygen.

Ubiquinone (CoQ) ❌

• A mobile electron carrier between Complex I/II and Complex III, not the final step.

FMN ❌

• Flavin mononucleotide is a prosthetic group in Complex I; it transfers electrons from NADH but does not interact with oxygen directly.

Cytochrome Q ❌

• Another name for ubiquinone (CoQ), which is not the terminal complex.

• In the electron transport chain (ETC), located in the inner mitochondrial membrane, the main function is to establish a proton gradient.

• As electrons pass through Complexes I, III, and IV, protons (H⁺) are pumped from the mitochondrial matrix into the intermembrane space.

• This creates an electrochemical proton gradient (proton motive force) across the inner mitochondrial membrane.

• The return flow of protons through ATP synthase (Complex V) drives the phosphorylation of ADP to ATP.

Why the other options are incorrect

O₂ ❌

• Oxygen is the final electron acceptor in Complex IV, reduced to water, but it does not cross into the intermembrane space.

CO₂ ❌

• Produced mainly in the TCA cycle within the matrix, but it is not part of the ETC proton pumping mechanism.

Mg²⁺ ❌

• Important as a cofactor for ATP-utilizing enzymes but not pumped in the ETC.

Ca²⁺ ❌

• Transported into mitochondria for signaling and metabolism regulation, but not by the ETC complexes.

• Free energy change (ΔG) of a reaction can be expressed in terms of redox potential (E₀′), especially in biological oxidation-reduction (redox) reactions.

• The relationship is given by the Nernst equation:

ΔG∘=−nFΔE∘\Delta G^\circ = -n F \Delta E^\circΔG∘=−nFΔE∘

where:

• n = number of electrons transferred

• F = Faraday’s constant

• ΔE° = change in redox potential

Thus, the energetics of electron transfer (like in the electron transport chain) are directly linked to ΔG.

Why the Other Options Are Wrong ❌

Exergonic reaction

• Means ΔG is negative (energy-releasing), but it is a type of reaction, not how free energy is expressed.

Reduction

• A chemical process of gaining electrons.

• Not a unit or expression of free energy.

Endergonic reaction

• Means ΔG is positive (energy-requiring), again a type of reaction, not the expression of free energy.

Oxidation

• Loss of electrons, but again a chemical process, not a way to express ΔG.

Tryptophan

• Niacin (Vitamin B3) can be synthesized in the body from the essential amino acid tryptophan.

• Approximately 60 mg of tryptophan can yield 1 mg of niacin equivalent (NE), provided vitamin B6 is available as a cofactor.

• This is why diets deficient in tryptophan (like maize-based diets) can lead to pellagra (dermatitis, diarrhea, dementia, and if untreated, death).

Why the Other Options Are Wrong ❌

Adenine

• A purine base found in nucleotides (ATP, DNA, RNA).

• Not related to niacin synthesis.

Tyrosine

• Precursor for catecholamines (dopamine, norepinephrine, epinephrine), thyroid hormones, and melanin.

• Not for niacin.

Methionine

• Sulfur-containing amino acid, important for methyl group transfers (via S-adenosyl methionine).

• Not a niacin precursor.

Phenylalanine

• Precursor of tyrosine → catecholamines, melanin.

• No role in niacin synthesis.

HMG CoA reductase

• The rate-limiting and regulatory step in endogenous cholesterol synthesis is catalyzed by HMG CoA reductase.

• Reaction:

  HMG-CoA  ⟶  MevalonateHMG\text{-}CoA \; \longrightarrow \; MevalonateHMG-CoA⟶Mevalonate

• This enzyme is tightly regulated by:

  • Feedback inhibition (by cholesterol and bile salts).

  • Hormonal control → Insulin ↑ activity, Glucagon ↓ activity.

  • Drug inhibition → Statins (competitive inhibitors of HMG CoA reductase).

Why the Other Options Are Wrong ❌

Glucose-6-phosphatase

• Enzyme of gluconeogenesis/glycogenolysis.

• Not involved in cholesterol synthesis.

Glycogen synthase

• Enzyme of glycogen synthesis.

• No role in cholesterol metabolism.

HMG CoA synthase

• Catalyzes formation of HMG CoA.

• Important step but not regulatory — the regulation happens at HMG CoA reductase.

Mevalonate

• Product of HMG CoA reductase action.

• Not an enzyme, so not the regulatory step.

• Cori’s disease (Glycogen Storage Disease type III) is caused by a deficiency of the debranching enzyme (α-1,6-glucosidase).

• Without this enzyme, glycogen breakdown is incomplete → abnormal glycogen with short outer chains accumulates.

• Clinical features: hepatomegaly, fasting hypoglycemia, muscle weakness, and growth retardation.

• Milder than Von Gierke’s disease (GSD type I), because gluconeogenesis is intact.

Why the Other Options Are Wrong ❌

Glycogen lyase (glycogen phosphorylase)

• Deficiency causes McArdle’s disease (GSD type V) with exercise-induced muscle cramps.

Glycogen synthase

• Deficiency would impair glycogen synthesis, not breakdown.

• Not related to Cori’s disease.

Pyruvate kinase

• Deficiency causes hemolytic anemia, not a glycogen storage disease.

Branching enzyme

• Deficiency causes Andersen’s disease (GSD type IV) with abnormal glycogen structure and liver cirrhosis.

Glutathione peroxidase

• Hydrogen peroxide (H₂O₂) is a reactive oxygen species (ROS) that can cause free radical damage.

• It is detoxified mainly by glutathione peroxidase, an enzyme that uses reduced glutathione (GSH) as a cofactor:

2 GSH+H2O2    ⟶    GSSG+2H2O2 \, GSH + H₂O₂ \;\; \longrightarrow \;\; GSSG + 2 H₂O2GSH+H2​O2​⟶GSSG+2H2​O

• This is a major antioxidant defense system inside cells.

Why the Other Options Are Wrong ❌

Glutathione oxidase

• No such enzyme in ROS defense. The enzyme is glutathione peroxidase, not oxidase.

Vitamin D

• Important for calcium/phosphate metabolism, not an antioxidant defense against free radicals.

Glutathione dismutase

• Doesn’t exist. Likely a distractor option.

Superoxide peroxidase

• Not a standard enzyme. The enzyme is superoxide dismutase (SOD), which converts superoxide radicals (O₂⁻•) into H₂O₂.

• But the question is about removing H₂O₂, so the correct answer is glutathione peroxidase.

Superoxide dismutase (SOD)

• Protects against superoxide radicals by converting them into H₂O₂, but then H₂O₂ itself must be removed by catalase or glutathione peroxidase.

Why this is correct

• The tricarboxylic acid (TCA) cycle, also known as the Krebs cycle or citric acid cycle, occurs in the mitochondrial matrix of eukaryotic cells.

• All the enzymes of the cycle are located in the matrix, except succinate dehydrogenase, which is bound to the inner mitochondrial membrane (and also part of the electron transport chain as Complex II).

• The mitochondrial location is crucial because:

  • NADH and FADH₂ generated by the cycle are immediately available for oxidative phosphorylation in the electron transport chain.

  • ATP production is tightly coupled to energy metabolism.

Why the other options are incorrect

Nucleus ❌

• Contains genetic material and enzymes for transcription/replication, not TCA enzymes.

Endoplasmic reticulum ❌

• Involved in protein and lipid synthesis, not energy metabolism.

Plasma membrane ❌

• In prokaryotes, parts of energy metabolism occur at the plasma membrane, but in eukaryotes, it’s the mitochondria.

Lysosomal bodies ❌

• Involved in degradation and recycling, not the TCA cycle.

Why this is correct

• In the mouth, digestion begins mainly through salivary enzymes:

  • Salivary amylase (ptyalin): starts hydrolyzing starch (amylose, amylopectin, complex carbohydrates) into maltose and dextrins.

  • Lingual lipase: begins limited digestion of triglycerides (especially important in infants).

• Proteins, however, are not digested in the mouth. Their digestion begins in the stomach with pepsin, which breaks peptide bonds.

Thus, proteins are the only option listed whose digestion does not begin in the oral cavity.

Why the other options are incorrect

Amylopectin ❌

• A branched polysaccharide; salivary amylase starts breaking α-1,4 glycosidic bonds in the mouth.

Complex carbohydrates ❌

• Includes starches (amylose and amylopectin); digestion begins in the mouth with amylase.

Amylose ❌

• A linear polysaccharide of glucose; digestion also begins in the mouth with salivary amylase.

Lipids ❌

• Lingual lipase secreted by glands of the tongue initiates lipid digestion in the mouth (though most occurs in the small intestine).

Why this is correct

• During fasting, the body needs to maintain blood glucose, especially for tissues like the brain and RBCs that rely heavily on glucose.

• The liver is the main organ responsible for this:

  • In the early hours of fasting (up to ~12–18 hours) → glycogenolysis (breakdown of stored liver glycogen) maintains blood glucose.

  • After glycogen stores are depleted → gluconeogenesis takes over for long-term maintenance.

• Muscle glycogen does not contribute to blood glucose because muscle lacks glucose-6-phosphatase, so it cannot release free glucose into the bloodstream.

Why the other options are incorrect

Erythrocyte glycolysis ❌

• RBCs use glycolysis to generate ATP (anaerobic), but this consumes glucose rather than maintaining it.

Muscle glycogenesis ❌

• Glycogenesis = synthesis of glycogen, a storage process, not glucose release.

Hexose monophosphate shunt (HMS) ❌

• Produces NADPH and ribose-5-phosphate, not glucose; not involved in maintaining blood glucose.

Tricarboxylic acid (TCA) cycle ❌

• Oxidizes acetyl-CoA for ATP production; no role in direct blood glucose maintenance.

Step 1: Purpose of the Urea Cycle

The urea cycle (in the liver) detoxifies ammonia (NH₃) by converting it into urea for safe excretion. Since ammonia is toxic to the CNS, regulation of this cycle is crucial.

🔹 Step 2: The Rate-Limiting Enzyme

• Carbamoyl phosphate synthetase I (CPS I) catalyzes the first committed step:

  NH3+CO2+2ATP→CarbamoylphosphateNH3​+CO2​+2ATP→Carbamoylphosphate

• This enzyme is located in the mitochondria.

• It requires N-acetylglutamate as an allosteric activator (without it, CPS I doesn’t function).

Thus, CPS I is the rate-limiting enzyme of the urea cycle.

🔹 Step 3: Why the Other Options Are Wrong

1. Argininosuccinate lyase ❌

   • Breaks down argininosuccinate into arginine + fumarate.

   • Important, but not rate-limiting.

2. Ornithine synthase ❌

   • Not an enzyme of the urea cycle (ornithine is recycled, not synthesized in this context).

3. Argininosuccinate synthase ❌

   • Combines citrulline + aspartate → argininosuccinate.

   • Necessary step, but not regulatory.

4. Ornithine transcarbamylase (OTC) ❌

   • Catalyzes carbamoyl phosphate + ornithine → citrulline.

   • Important enzyme, but not rate-limiting.

Glycogenolysis = breakdown of glycogen into glucose.

1. Glycogen phosphorylase

   • Cleaves α-1,4 glycosidic bonds at the nonreducing ends of glycogen.

   • Produces glucose-1-phosphate (G1P). ✅

   • Stops when it gets 4 glucose residues away from a branch point.

2. Debranching enzyme

   • Has 2 activities:

     • Transferase activity → shifts a block of 3 glucose residues to another chain.

     • Glucosidase activity → hydrolyzes the α-1,6 bond, releasing free glucose (not G1P).

   • So, it helps deal with branch points but does not release G1P directly.

3. Glycogen synthase

   • Builds glycogen by forming α-1,4 bonds during glycogenesis. ❌

4. Branching enzyme

   • Creates α-1,6 bonds in glycogenesis (introduces branches). ❌

5. Glucose-6-phosphatase

   • Converts glucose-6-phosphate → free glucose in the liver for release into blood.

   • Final step of gluconeogenesis/glycogenolysis, but not the enzyme that cleaves glycogen. ❌

What is the Glycemic Index (GI)?

• GI is a ranking system for carbohydrate-containing foods.

• It measures how quickly and how much a food raises blood glucose after consumption compared to a reference (usually glucose or white bread).

• High-GI foods → rapid spike in blood glucose.

• Low-GI foods → slower, gradual increase.

Option-by-Option Analysis

1. The ability of the liver to maintain blood glucose levels ❌

   • Wrong. This describes hepatic glucose regulation, not GI.

2. The ability of food to increase blood glucose levels ✅

   • Correct. GI is all about postprandial blood glucose rise after eating a food.

3. The ability of the liver to increase blood glucose levels ❌

   • Wrong. This is more about glycogenolysis or gluconeogenesis, unrelated to GI.

4. The ability of the liver to reduce blood glucose levels ❌

   • Wrong. That would be insulin-mediated glucose uptake or glycogenesis.

5. The ability of food to reduce blood glucose levels ❌

   • Wrong. No food directly reduces glucose levels; GI measures the increase in glucose.

Cholesterol synthesis is a multi-step process that begins with acetyl-CoA in the cytoplasm and proceeds through several enzymatic steps until cholesterol is formed. The key regulatory step — the “bottleneck” of the pathway — is:

• HMG-CoA → Mevalonate
  catalyzed by HMG-CoA reductase.

This is the rate-limiting step, tightly regulated by:

• Feedback inhibition (by cholesterol and its derivatives).

• Hormonal control (insulin ↑ activity, glucagon ↓ activity).

• Pharmacologic inhibition (statins are competitive inhibitors of HMG-CoA reductase).

❌ Why the Other Options Are Incorrect:

• Mevalonate carboxylase → Not part of the cholesterol synthesis regulation.

• Prenyl transferase → Involved in later steps (isoprenoid condensation), but not rate-limiting.

• Squalene synthase → Catalyzes the formation of squalene from farnesyl pyrophosphate, important but not the committed step.

• HMG-CoA synthase → Converts acetyl-CoA to HMG-CoA, but this is before the committed step. Its role is important, but not regulatory for cholesterol synthesis.

Amino acids can be classified based on their metabolic fate:

• Glucogenic amino acids → Their catabolism produces intermediates like pyruvate, oxaloacetate, α-ketoglutarate, succinyl-CoA, or fumarate — all of which can enter gluconeogenesis.

• Ketogenic amino acids → Their breakdown produces acetyl-CoA or acetoacetate. These cannot contribute to net glucose synthesis because acetyl-CoA cannot be converted back into pyruvate or oxaloacetate (the pyruvate dehydrogenase reaction is irreversible).

• Both glucogenic and ketogenic → Some amino acids can yield products that go into both pathways.

The purely ketogenic amino acids are:

• Leucine

• Lysine

These are the ones that cannot contribute carbons for gluconeogenesis.

Why the other options are wrong

Semi-essential ❌
This classification is based on dietary requirement (e.g., arginine, histidine) — not on metabolic fate. Irrelevant here.

Non-essential ❌
Non-essential amino acids can be synthesized by the body; some are glucogenic. This is a nutritional category, not about metabolism to acetyl-CoA.

Essential ❌
Essential amino acids must be obtained from the diet. Some essential amino acids are glucogenic, some ketogenic, and some both. So this term does not specifically answer the question.

Glucogenic ❌
Glucogenic amino acids can be converted into glucose precursors (via pyruvate, oxaloacetate, etc.). The question specifically asks about amino acids that cannot be used for gluconeogenesis, so this is the opposite.

Ketogenic ✅
They yield only acetyl-CoA or acetoacetate, which cannot enter gluconeogenesis. Correct answer.

Cholesterol biosynthesis starts from acetyl-CoA and proceeds through a series of enzymatic reactions:

1. Acetyl-CoA → HMG-CoA
   (via HMG-CoA synthase)

2. HMG-CoA → Mevalonate
   (via HMG-CoA reductase)

   • This is the rate-limiting step.

   • It is tightly regulated by cholesterol levels, hormones (↑ insulin, ↓ glucagon), and drugs (statins inhibit this enzyme).

3. Mevalonate → Isopentenyl pyrophosphate (IPP)

4. IPP → Farnesyl pyrophosphate

5. Farnesyl → Squalene

6. Squalene → Lanosterol → Cholesterol

Thus, the critical checkpoint is the conversion of HMG-CoA to mevalonate, not the steps before or after.

Why the other options are wrong

• Synthesis of farnesyl ❌
  A later intermediate; not rate-limiting.

• Synthesis of mevalonate ✅
  Catalyzed by HMG-CoA reductase; the true rate-limiting step.

• Synthesis of HMG-CoA ❌
  Occurs earlier, but not the regulated/committed step.

• Synthesis of squalene ❌
  Further downstream; too late to be controlling.

• Synthesis of isopentenyl pyrophosphate (IPP) ❌
  Comes after mevalonate; not the main regulatory point

Vitamin B6 exists in several forms:

• Pyridoxine (alcohol form)

• Pyridoxal (aldehyde form)

• Pyridoxamine (amine form)

All of these are precursors that must be converted into the biologically active coenzyme:

👉 Pyridoxal 5-phosphate (PLP)

Functions of PLP:

• Coenzyme for transamination, decarboxylation, and glycogen phosphorylase reactions.

• Involved in synthesis of neurotransmitters (dopamine, serotonin, GABA), heme, niacin (from tryptophan).

Clinical correlation:

• Deficiency → irritability, seizures, neuropathy, anemia (sideroblastic), and pellagra-like symptoms.

• Can be caused by isoniazid (which inactivates PLP).

Why the other options are wrong

NAD ❌

• Derived from niacin (vitamin B3), not B6.

Pyridoxal 5-phosphate ✅

• Correct — the active coenzyme form of B6.

Pyridoxine ❌

• One of the dietary forms, but must be phosphorylated to PLP to be active.

FMN ❌

• Flavin mononucleotide, derived from riboflavin (vitamin B2), not B6.

Pyridoxamine ❌

• Another form of B6, but inactive until converted to PLP.

🔎 Step 1: Understanding Gluconeogenesis vs Glycolysis

• Glycolysis: Breakdown of glucose to pyruvate; certain steps are irreversible.

• Gluconeogenesis: Synthesis of glucose from non-carbohydrate precursors; bypasses irreversible glycolytic steps using specific enzymes.

Key irreversible glycolytic steps and their gluconeogenic bypasses:

Other steps are reversible and shared between glycolysis and gluconeogenesis.

✅ Correct Answer: Conversion of pyruvate to phosphoenolpyruvate

• This reaction is unique to gluconeogenesis and bypasses the irreversible glycolytic step catalyzed by pyruvate kinase.

• It occurs via two enzymes:

  1. Pyruvate carboxylase: Pyruvate → Oxaloacetate (OAA)

  2. PEP carboxykinase: OAA → Phosphoenolpyruvate (PEP)

• This step does not occur in glycolysis, which goes in the opposite direction (PEP → pyruvate).

❌ Why the Other Options Are Incorrect

• Fructose-6-phosphate → Fructose-1,6-bisphosphate → Glycolysis step, not unique to gluconeogenesis.

• Dihydroxyacetone → Glyceraldehyde-3-phosphate → Reversible; occurs in both glycolysis and gluconeogenesis.

• Fumarate → Malate → Part of TCA cycle, not a gluconeogenic-specific reaction.

• Glucose → Glucose-6-phosphate → Glycolysis step, not unique to gluconeogenesis.

🔎 Step 1: Interpreting the Clinical Picture

• Patient: 40-year-old man

• Symptoms: Fever (102°F), abdominal pain, diarrhea, pale skin

• Laboratory finding: Elevated liver enzymes

This presentation suggests hepatocellular injury likely due to infectious hepatitis or another acute liver insult.

🔎 Step 2: Liver Enzymes

Key liver enzymes and their significance:

• Alanine aminotransferase (ALT) → Found predominantly in hepatocytes; highly specific for liver injury.

• Aspartate aminotransferase (AST) → Found in liver, heart, muscle, kidney, RBCs; less liver-specific.

• Lactate dehydrogenase (LDH) → Found in many tissues; elevated in hemolysis, tissue injury.

• Creatine kinase (CK) → Muscle enzyme; not specific for liver.

• Glutamate kinase → Not a standard liver function test; likely a distractor.

✅ Correct Answer: Alanine aminotransferase (ALT)

• ALT is the most specific marker of hepatocellular damage.

• In hepatitis (viral, bacterial, or toxic), ALT rises markedly, often more than AST.

• Other clinical clues (fever, abdominal pain, diarrhea, pale skin) support an infectious process affecting the liver.

❌ Why the Other Options Are Incorrect

• Lactate carboxylase → Likely intended as lactate dehydrogenase (LDH); nonspecific, elevated in many tissues.

• Glutamate kinase → Not a standard liver enzyme.

• Creatinine kinase (CK) → Muscle-specific; not liver-specific.

• Aspartate dehydrogenase → Likely intended as AST; less liver-specific than ALT.

🔎 Step 1: Recall the Electron Transport Chain (ETC)

• The ETC is a series of protein complexes in the inner mitochondrial membrane that transfer electrons from reduced cofactors (NADH, FADH2) to oxygen, generating a proton gradient for ATP synthesis.

• Key complexes:

  1. Complex I: NADH–coenzyme Q reductase → accepts electrons from NADH

  2. Complex II: Succinate–coenzyme Q reductase → accepts electrons from FADH2

  3. Complex III: Coenzyme Q–cytochrome c reductase

  4. Complex IV: Cytochrome c oxidase → transfers electrons to O2

✅ Correct Answer: NADH–coenzyme Q reductase

• This is Complex I of the ETC.

• Function:

  • Accepts a pair of electrons from NADH

  • Transfers them to coenzyme Q (ubiquinone)

  • Pumps protons into the intermembrane space to help generate the proton gradient

❌ Why the Other Options Are Incorrect

• Cytochrome c oxidase (Complex IV) → Accepts electrons from cytochrome c, reduces O2 to water; does not directly accept electrons from NADH.

• Succinate–coenzyme Q reductase (Complex II) → Accepts electrons from FADH2 (from succinate), not NADH.

• Coenzyme Q–cytochrome c reductase (Complex III) → Accepts electrons from reduced coenzyme Q, not directly from NADH.

🔎 Step 1: Recall the Chemiosmotic Theory

• Proposed by Peter Mitchell, the chemiosmotic theory explains how ATP is generated in mitochondria during oxidative phosphorylation.

• Key points:

  • Electron transport through Complexes I–IV of the electron transport chain (ETC) pumps protons (H⁺) from the mitochondrial matrix into the intermembrane space.

  • This creates a proton gradient (electrochemical potential).

  • Protons flow back into the matrix via ATP synthase, driving the synthesis of ATP from ADP + Pi.

✅ Correct Answer: Proton gradient

• The proton-motive force across the inner mitochondrial membrane is the central concept of chemiosmosis.

• Without the proton gradient, ATP synthase cannot generate ATP, regardless of the presence of electrons.

❌ Why the Other Options Are Incorrect

• Glycolysis → Generates ATP via substrate-level phosphorylation, not chemiosmosis.

• Beta-oxidation → Produces NADH and FADH2, which feed electrons into the ETC, but does not directly generate ATP via chemiosmosis.

• NADH+ transport → NADH donates electrons, but ATP is not generated simply by NADH transfer; it’s the proton gradient that drives ATP synthesis.

• Ca⁺ concentration → Calcium ions are not involved in ATP generation via chemiosmosis.

🔎 Step 1: Glycolysis and Energy Regulation

• Glycolysis breaks down glucose to pyruvate, producing ATP.

• Several enzymes are key regulatory points, often called rate-limiting steps:

  1. Hexokinase / Glucokinase: Glucose → Glucose-6-phosphate

  2. Phosphofructokinase-1 (PFK-1): Fructose-6-phosphate → Fructose-1,6-bisphosphate

  3. Pyruvate kinase: Phosphoenolpyruvate → Pyruvate

• Regulation depends on energy status:

  • High ATP → inhibits glycolysis

  • Low ATP / high AMP → activates glycolysis

✅ Correct Answer: Phosphofructokinase (PFK-1)

• PFK-1 is the rate-limiting enzyme of glycolysis.

• Activated by low ATP / high AMP, ensuring glycolysis proceeds when the cell needs energy.

• Inhibited by high ATP and citrate.

❌ Why the Other Options Are Incorrect

• Isomerase (phosphoglucose isomerase) → Catalyzes a reversible step; not rate-limiting; not regulated by ATP.

• Pyruvate kinase → Final step enzyme; regulated by fructose-1,6-bisphosphate (feed-forward) and ATP, but PFK-1 is the main energy-sensing enzyme.

• Hexokinase → Catalyzes first step; inhibited by its product (G6P), not directly by ATP levels.

• Glucokinase → Liver isoform; not sensitive to ATP; regulated by glucose levels and glucokinase regulatory protein.

Cytochrome c transfers electrons from Complex III to Complex IV (cytochromes a and a₃).

In this patient:

• The insecticide completely inhibits cytochrome c

• Electrons cannot move from Complex III to Complex IV

Consequences:

• Upstream of the block (Complex III and earlier)
  → electrons accumulate → reduced state

• Downstream of the block (Complex IV)
  → no electrons arrive → oxidized state

• ATP synthesis decreases, leading to respiratory failure

Therefore, Complex III remains reduced, making it the correct answer.

❌ Incorrect Options Explained

❌ Coenzyme Q would be in the oxidized state

• CoQ is upstream of cytochrome c

• It would accumulate electrons → reduced, not oxidized

❌ Complex I would be in oxidized state

• Complex I is also upstream

• NADH cannot pass electrons forward → Complex I becomes reduced

❌ Cytochromes a and a₃ would be in the reduced state

• These are part of Complex IV

• Since electrons never reach them, they remain oxidized

❌ The rate of ATP synthesis would be increased

• Electron flow is blocked

• Proton pumping falls

• ATP synthesis decreases, not increases

Correct Answer: NADH+H⁺ / NAD ✅

• The energy level of a biological system depends on how much reducing power (electrons) is available for ATP production.

• A high NADH/NAD ratio means lots of reduced cofactors are present → plenty of electrons to donate to the electron transport chain → high energy state.

• Conversely, a low ratio means the cell is oxidized and energy-depleted.

Why the Others Are Incorrect

• ADP/ATP ❌ – High ADP/ATP indicates low energy, because ATP is being used up.

• AMP/ADP ❌ – Similarly, high AMP relative to ADP signals an energy-poor state (sensed by AMPK).

• Glucagon/Insulin ❌ – This reflects hormonal status (fasting vs fed), not direct intracellular energy state.

• NADPH+H⁺/NADP ❌ – This ratio indicates reducing power for biosynthetic pathways (fatty acid, cholesterol synthesis, antioxidant defense), not general cellular energy.

Correct Answer: It causes the gallbladder to contract and release stored bile into the intestine ✅

• CCK is secreted by I-cells of the duodenum and jejunum in response to fatty acids and amino acids.

• Its primary role in fat digestion is to make the gallbladder contract and the sphincter of Oddi relax, so bile (containing bile salts and phospholipids) is released into the intestine.

• This bile emulsifies fats → facilitates micelle formation → enables absorption.

Why the Others Are Incorrect

• It increases the production of bile by the liver ❌ – Bile production is continuous, mainly regulated by secretin and hepatic bile acid return. CCK releases stored bile, not produce new bile.

• It promotes the absorption of bile salts in the ileum ❌ – That’s a passive/active transport process in the terminal ileum, independent of CCK.

• It induces gastric acid secretion to protect the intestines ❌ – Opposite effect: CCK actually slows gastric emptying. Gastric acid secretion is mainly stimulated by gastrin.

• It stimulates the pancreas to release insulin for fat digestion ❌ – Insulin regulates glucose metabolism, not fat digestion. CCK does stimulate pancreatic enzyme secretion, but not insulin.

Correct Answer: Cholecystokinin (CCK) ✅

• CCK is released from I-cells in the duodenum and jejunum when fatty acids and amino acids enter the small intestine.

• Its major actions:

  • Stimulates the pancreas to secrete enzyme-rich juice (lipases, proteases, amylase).

  • Causes gallbladder contraction → bile release.

  • Slows gastric emptying so digestion can proceed efficiently.

Why the Others Are Incorrect

• Gastrin ❌ – Mainly stimulates gastric acid secretion and gastric motility; weak effect on pancreas.

• Glucagon ❌ – Hormone of fasting; increases blood glucose. No direct role in pancreatic enzyme secretion.

• Insulin ❌ – Regulates blood glucose uptake/storage; not related to digestive enzyme secretion.

• Secretin ❌ – Released in response to acidic chyme; stimulates the pancreas to secrete bicarbonate-rich fluid, not enzymes.

Correct Answer: Alkaptonuria ✅

• Key clues:

  • Dark urine that turns black on standing/exposure to air → hallmark of homogentisic acid buildup.

  • Benedict’s test positive but glucose negative → presence of a reducing substance that is not glucose (here, homogentisic acid).

  • Defect: deficiency of homogentisate oxidase, leading to accumulation of homogentisic acid in urine.

Why the Others Are Incorrect

• Galactosemia ❌ – Would also give a positive Benedict’s test (due to galactose), but urine does not turn black. More typical presentation: vomiting, jaundice, hepatomegaly, cataracts.

• Maple syrup urine disease ❌ – Urine smells like burnt sugar/maple syrup, not black discoloration. Caused by branched-chain α-ketoacid dehydrogenase deficiency.

• Phenylketonuria (PKU) ❌ – Presents with musty/mousy odor of urine, intellectual disability, seizures, hypopigmentation. No black urine.

• Tyrosinemia ❌ – Causes liver and kidney dysfunction; may cause a cabbage-like odor, but not urine blackening.

THE LAST TIME IS NOW for JOHN CENA

Correct Answer: Stored fat ✅

• After ~48 hours of fasting:

  • Glycogen is depleted (usually gone after ~24 hours).

  • The body shifts to lipolysis: adipose tissue breaks down triglycerides into fatty acids + glycerol.

  • Fatty acids → main energy source for most tissues.

  • Ketone bodies begin to rise, especially for the brain.

Why the Others Are Incorrect

• Amino acids from muscle ❌ – Used for gluconeogenesis, but the body spares muscle as much as possible. Fat is the primary energy source.

• Excess glucose ❌ – There is no “excess” glucose during fasting; blood glucose is maintained just enough via gluconeogenesis.

• Dietary carbohydrates ❌ – None are available, since Ali is fasting.

• Tripeptides ❌ – Not a physiological energy source; proteins are broken down into amino acids, not directly used as peptides.

Correct Answer: Phenylalanine hydroxylase ✅

• Phenylalanine hydroxylase converts phenylalanine → tyrosine in the liver.

• This requires the cofactor tetrahydrobiopterin (BH₄).

• Deficiency of this enzyme (or BH₄) → Phenylketonuria (PKU).

Why the Others Are Incorrect

• Homogentisate oxidase ❌ – Involved in tyrosine metabolism (homogentisate → maleylacetoacetate). Deficiency causes alkaptonuria, not PKU.

• Homogentisate reductase ❌ – No such enzyme in this pathway.

• Phenylalanine oxidase ❌ – Not the correct enzyme name; sometimes confused terminology, but the enzyme in humans is phenylalanine hydroxylase.

• Tyrosine transaminase ❌ – Converts tyrosine → p-hydroxyphenylpyruvate in tyrosine catabolism, not phenylalanine metabolism.

Correct Answer: Thiamine pyrophosphate (TPP) ✅

• The active coenzyme form of Vitamin B1 (thiamine) is thiamine pyrophosphate (TPP).

• TPP is essential in oxidative decarboxylation reactions, such as:

  • Pyruvate dehydrogenase (pyruvate → acetyl-CoA)

  • α-ketoglutarate dehydrogenase (TCA cycle)

  • Branched-chain α-ketoacid dehydrogenase (BCAA metabolism)

  • Transketolase (pentose phosphate pathway)

Why the Others Are Incorrect

• Tetrahydrothiamine ❌ – Not an actual biologically active form.

• Thiamine diphosphate ❌ – Sometimes used interchangeably, but the correct biochemical name is thiamine pyrophosphate (TPP).

• Thiamine monophosphate ❌ – Exists but is not the active coenzyme form.

• Thiamine triphosphate ❌ – Present in tissues, thought to have a role in nerve conduction, but not the key metabolic coenzyme form.

Correct Answer: Glycogen phosphorylase (myophosphorylase) ✅

• McArdle’s disease (Glycogen Storage Disease type V) is caused by deficiency of muscle glycogen phosphorylase (myophosphorylase).

• This enzyme normally cleaves glycogen to produce glucose-1-phosphate during exercise.

• Without it, muscle cannot mobilize glycogen → energy crisis during exertion, leading to exercise intolerance, muscle cramps, and myoglobinuria.

Why the Others Are Incorrect

• Acid α-glucosidase ❌ – Deficient in Pompe’s disease (GSD II); leads to glycogen buildup in lysosomes, causing cardiomegaly and hypotonia, not exercise cramps.

• Debranching enzyme ❌ – Deficient in Cori’s disease (GSD III); results in mild hypoglycemia and hepatomegaly, not specific exercise-induced cramps.

• Glucose-6-phosphatase ❌ – Deficient in Von Gierke’s disease (GSD I); causes severe fasting hypoglycemia, lactic acidosis, and hepatomegaly.

• Phosphorylase kinase ❌ – Deficient in Hers disease (GSD IX); leads to hepatomegaly and growth retardation, not classic exercise cramps.

Correct Answer: Acetyl CoA and oxaloacetate ✅

• The TCA cycle (Krebs cycle) starts when acetyl CoA (2C) combines with oxaloacetate (4C) → forming citrate (6C).

• This reaction is catalyzed by citrate synthase.

• Citrate then undergoes isomerization and further oxidation steps to generate NADH, FADH₂, GTP, and CO₂.

Why the Others Are Incorrect

• Succinate and pyruvate ❌ – Succinate (4C) is an intermediate in the cycle; pyruvate (3C) must first be converted to acetyl CoA by pyruvate dehydrogenase. They don’t directly condense.

• Fumarate and pyruvate ❌ – Fumarate (4C) is later in the cycle; it doesn’t react with pyruvate.

• Succinate and malate ❌ – Both are cycle intermediates but never combine directly.

• Acetyl CoA and malate ❌ – Malate is converted to oxaloacetate before condensing with acetyl CoA.

Correct Answer: Glucose-6-phosphate dehydrogenase (G6PD) ✅

• The rate-limiting enzyme of the pentose phosphate pathway (hexose monophosphate shunt) is G6PD.

• It catalyzes: Glucose-6-phosphate → 6-phosphogluconolactone.

• NADP⁺ acts as an allosteric activator, while NADPH provides feedback inhibition.

• This step is crucial for generating NADPH (used in fatty acid synthesis, glutathione reduction) and ribose-5-phosphate (for nucleotide synthesis).

Why the Others Are Incorrect

• Ribose-5-phosphate isomerase ❌ – Converts ribose-5-phosphate ↔ ribulose-5-phosphate; not rate-limiting.

• Ribulose-5-phosphate 3-epimerase ❌ – Converts ribulose-5-phosphate ↔ xylulose-5-phosphate; a reversible step, not regulatory.

• Transaldolase ❌ – Involved in rearranging carbon skeletons (non-oxidative phase), but not rate-limiting.

• Transketolase ❌ – Also catalyzes carbon shuffling (requires thiamine/TPP), important but not the control point.

Correct Answer: Liver failure ✅

• Intestinal bacteria produce urease, which breaks down urea → ammonia (NH₃).

• Normally, the liver rapidly converts ammonia → urea via the urea cycle.

• In liver failure, this detoxification is impaired → ammonia accumulates → hyperammonemia → hepatic encephalopathy.

• Thus, the action of intestinal urease becomes clinically significant in worsening symptoms.

Why the Others Are Incorrect

• Renal failure ❌ – Problem is impaired excretion of urea/creatinine, not ammonia detoxification.

• Hepatic toxicity ❌ – A broad term; the specific issue is failure of detoxification in chronic liver failure.

• Renal injury ❌ – Again, leads to uremia, not hyperammonemia from urease activity.

• Autoimmune diseases ❌ – No direct link to urease-related ammonia buildup.

Correct Answer: NAD ✅

• The reaction lactate → pyruvate is catalyzed by lactate dehydrogenase.

• This requires NAD⁺ as a hydrogen acceptor (oxidized form).

• In the process:

  • Lactate is oxidized to pyruvate.

  • NAD⁺ is reduced to NADH + H⁺.

• This reaction is important in the Cori cycle, allowing lactate (from muscle/RBCs) to be converted back to glucose in the liver.

Why the Others Are Incorrect

• Haemoglobin ❌ – Oxygen carrier, not an electron carrier in this reaction.

• FAD ❌ – Coenzyme for other dehydrogenases (e.g., succinate dehydrogenase), not lactate dehydrogenase.

• FMN ❌ – Part of Complex I in ETC, not used here.

• Cytochrome a ❌ – Component of Complex IV in ETC, not involved in cytosolic lactate oxidation.

Correct Answer: Hormone-sensitive lipase ✅

• After 8 days of fasting, glycogen stores are long gone (depleted after ~24 hours).

• The body shifts to lipolysis as the primary energy source.

• Hormone-sensitive lipase (HSL) in adipose tissue is activated by low insulin / high glucagon & epinephrine, breaking triglycerides → free fatty acids + glycerol.

• Free fatty acids fuel most tissues (via β-oxidation), while glycerol goes to the liver for gluconeogenesis.

Why the Others Are Incorrect

• Glucokinase ❌ – Active in the fed state, phosphorylates glucose in the liver. Fasting = low glucose, so not active.

• Hexokinase ❌ – Works in most tissues but only when glucose is available; after 8 days fasting, glucose is minimal.

• Pyruvate dehydrogenase ❌ – Converts pyruvate → acetyl-CoA, but gluconeogenesis dominates during prolonged fasting; PDH is relatively suppressed.

• Lipoprotein lipase ❌ – Hydrolyzes triglycerides in circulating chylomicrons/VLDL (fed state), not during prolonged fasting.

Why this is correct:
A 1-week-old with poor feeding, vomiting, lethargy/somnolence, and rapid breathing after a few symptom-free days strongly suggests a urea cycle defect causing hyperammonemia. Ammonia is neurotoxic and triggers central hyperventilation → respiratory alkalosis. A normal anion gap fits (there isn’t a primary metabolic acidosis), making urea cycle errors the classic neonatal emergency here.

Why the others are incorrect

• Homocystinemia due to cystathionase deficiency ❌
  Typically presents later in childhood (marfanoid habitus, lens subluxation, thrombosis). Not a neonatal hyperacute picture; no link to normal anion gap respiratory alkalosis.

• Hypoglycemia due to glucose-6-phosphatase deficiency (Von Gierke) ❌
  Presents after the neonatal period with severe fasting hypoglycemia, lactic acidosis (↑ anion gap), hyperuricemia, hepatomegaly—not isolated early respiratory alkalosis.

• Long-chain fatty acids accumulation due to carnitine deficiency ❌
  Causes hypoketotic hypoglycemia, lethargy, seizures, cardiomyopathy; acid–base may show metabolic derangements, not a normal anion gap respiratory alkalosis.

• Phenylketonuria due to phenylalanine hydroxylase deficiency ❌
  Insidious onset after weeks–months (musty odor, eczema, developmental delay). Not an acute neonatal crisis with tachypnea and normal anion gap.

What the patient has

The triad of dermatitis (photosensitive, hyperpigmented/scaly rash around exposed areas), glossitis (beefy red tongue), and generalized weakness in someone eating mostly maize points strongly to pellagra — niacin (vitamin B3) deficiency. Lab confirmation of low niacin supports the clinical diagnosis.

Why maize (corn) causes pellagra

• Niacin (nicotinic acid / nicotinamide) can be obtained directly from diet or synthesized de novo from the essential amino acid tryptophan in the body.

• Maize-based diets are problematic two ways:

  • Maize is low in tryptophan, so there’s reduced substrate for endogenous niacin synthesis.

  • In untreated maize, some niacin is bound and not bioavailable unless the corn is processed (e.g., nixtamalization — treatment with alkali, used in traditional Mesoamerican preparation).

• The net result in populations relying primarily on unprocessed maize and little animal protein: insufficient niacin → pellagra.

Biochemical detail (concise)

• Conversion: tryptophan → niacin (NAD⁺ precursor) requires cofactors (e.g., vitamin B6). Insufficient tryptophan reduces niacin production and therefore NAD⁺/NADP⁺ pools needed for many metabolic reactions — explaining the systemic manifestations.

Why the other options are less likely or incorrect

• Genetic defect in tryptophan absorption (Hartnup disease)

  • Hartnup causes pellagra-like features due to impaired neutral amino acid (including tryptophan) absorption and increased urinary loss. It is genetic and typically presents earlier in life with episodic photosensitive rash and ataxia; history here (longstanding maize diet, adult onset) makes dietary deficiency far more likely.

• Excessive diversion of tryptophan into serotonin synthesis (carcinoid syndrome)

  • Carcinoid tumors can shunt tryptophan to serotonin and cause pellagra, but that is uncommon and would usually have other features (flushing, diarrhea, bronchospasm). No such features are described here.

• Increased urinary excretion of niacin due to renal tubular disorder

  • Renal losses of niacin are not a typical or common cause of pellagra; the history points to deficient intake/substrate rather than renal wasting.

• Reduced intestinal bacterial production of niacin due to antibiotics

  • Gut flora can contribute some niacin, but antibiotic suppression causing frank pellagra is rare and would be less likely than the strong dietary explanation given (maize diet with little animal protein).

Clinical takeaways

• In a patient with pellagra features and a maize-based diet, the primary cause is dietary niacin deficiency due to lack of tryptophan and low bioavailability of niacin in corn.

• Management: niacin (nicotinamide) supplementation, improve dietary protein intake, and address any cofactors (e.g., vitamin B6). Educate about processing maize (nixtamalization) or dietary diversification.

• In the electron transport chain (ETC), electrons are passed from NADH and FADH₂ through a series of complexes (I–IV).

• At Complex IV (cytochrome c oxidase), the electrons are finally transferred to molecular oxygen (O₂).

• Oxygen combines with electrons and protons (H⁺) to form water.

• Without oxygen, the ETC cannot operate, oxidative phosphorylation halts, and ATP production collapses → that’s why oxygen is called the final electron acceptor.

Why the others are wrong

• Carbon dioxide ❌ – It’s a product of the Krebs cycle, not the final electron acceptor.

• FADH₂ ❌ – It donates electrons to the ETC at Complex II, not the final acceptor.

• Hydrogen ❌ – Protons are used in chemiosmosis, but not the final acceptor.

• NADH ❌ – Donates electrons at Complex I, not the final acceptor.

• Oxygen ✅ – Correct → accepts electrons at the end of the chain to form water.

• Massive obesity + dyspnea → strongly suggests Obesity Hypoventilation Syndrome (OHS), also known as Pickwickian syndrome.

• In OHS:

  • Excess body weight restricts diaphragm and chest wall movement.

  • This leads to alveolar hypoventilation → patient cannot blow off CO₂ effectively.

  • Result = hypercapnia (↑ CO₂ retention).

• Acid–base status:

  • ↑ CO₂ combines with water → carbonic acid → dissociates into H⁺ and HCO₃⁻.

  • This lowers pH → respiratory acidosis.

  • Kidneys try to compensate by retaining more bicarbonate (↑ HCO₃⁻), but the primary defect is CO₂ retention.

Why not the others

• Decreased HCO₃⁻ retention ❌ – That’s metabolic acidosis (like DKA), but here the problem is hypoventilation, not ketoacids.

• Decreased CO₂ retention ❌ – Seen in hyperventilation (respiratory alkalosis).

• O₂ retention changes ❌ – Not the key metabolic shift; hypoxemia can occur, but it’s not the defining acid–base change.

• During fasting, blood glucose levels must be maintained for glucose-dependent tissues (like the brain and RBCs).

• The liver is the primary organ responsible for regulating glucose during fasting:

  • In short-term fasting (up to ~12 hrs) → liver maintains glucose via glycogenolysis (breakdown of glycogen).

  • In prolonged fasting (>12–24 hrs) → glycogen stores are depleted → liver produces glucose through gluconeogenesis (from lactate, glycerol, and amino acids).

• Other tissues:

  • Smooth muscle ❌ – Consumes glucose but does not release it into blood (no glucose-6-phosphatase).

  • Brain ❌ – Only consumes glucose (and ketones later), cannot regulate blood glucose.

  • Bone ❌ – No role in glucose homeostasis.

  • Red blood cells ❌ – Rely only on glycolysis for energy, cannot regulate blood glucose.

• Erythrocytes (RBCs) lack mitochondria.

• That means they cannot perform the TCA cycle or oxidative phosphorylation, so pyruvate cannot be fully oxidized to CO₂.

• Instead, RBCs rely only on anaerobic glycolysis (Embden–Meyerhof pathway, EMP) for ATP.

• In this pathway, pyruvate is converted to lactate by lactate dehydrogenase (LDH).

• This regenerates NAD⁺, allowing glycolysis to continue.

Now check the options:

• Lactate ✅ – Correct product in RBCs.

• CO₂ ❌ – Requires mitochondria (via TCA cycle), which RBCs don’t have.

• Ethanol ❌ – Produced in yeast, not humans.

• Hemoglobin ❌ – A protein, not a product of glycolysis.

• Bilirubin ❌ – Produced from heme breakdown, unrelated to pyruvate metabolism.

• Oxidative phosphorylation takes place in the mitochondrial inner membrane.

• It couples the electron transport chain (ETC) with ATP synthesis via ATP synthase.

• Final outcomes:

  • ATP → produced as protons flow back through ATP synthase.

  • H₂O → produced when oxygen acts as the final electron acceptor and combines with H⁺ and electrons.

Now check the options:

• NADH ❌ – It is consumed (oxidized) in ETC, not formed.

• Oxygen ❌ – It is consumed as the final electron acceptor, not formed.

• ADP ❌ – Substrate that gets phosphorylated, not a product.

• Pyruvate ❌ – Product of glycolysis, enters TCA, not made by oxidative phosphorylation.

• ATP + H₂O ✅ – End products of oxidative phosphorylation.

• PKU is caused by deficiency of phenylalanine hydroxylase (or its cofactor tetrahydrobiopterin).

• Leads to ↑ phenylalanine and accumulation of its toxic metabolites (phenylpyruvate, phenylacetate, phenyllactate).

• These cause CNS damage, seizures, mental retardation, and mousy odor of urine.

• Lack of tyrosine formation also reduces melanin → hypopigmentation (fair skin, hair, eyes).

Other options:

• Alkaptonuria (AKU) ❌ – Due to homogentisate oxidase deficiency, causes dark urine on standing, ochronosis, arthritis.

• Albinism ❌ – Pure defect in melanin synthesis (tyrosinase deficiency), no seizures or mousy odor.

• Hawkinsiuria ❌ – Rare tyrosine metabolism disorder, not linked with mousy odor.

• Tyrosinemia ❌ – Liver/kidney failure, cabbage-like odor, not mousy odor.

• Kernicterus = bilirubin encephalopathy in neonates.

• In newborns, the blood-brain barrier is immature, and albumin-binding capacity is limited.

• When unconjugated (indirect) bilirubin levels rise excessively → bilirubin crosses into the basal ganglia and brainstem nuclei.

• Being lipid-soluble, unconjugated bilirubin deposits in brain tissue → neurotoxicity → poor feeding, high-pitched cry, lethargy, seizures, apnea.

• Direct (conjugated) bilirubin is water-soluble and does not cross the blood-brain barrier, so it does not cause kernicterus.

Why the others are wrong

• Direct bilirubin in the brain ❌ – Water-soluble, cannot cross BBB.

• Total bilirubin in brain and liver ❌ – Misleading; the toxic part is indirect bilirubin in brain.

• Indirect bilirubin in the liver ❌ – The problem is not liver deposition but CNS deposition.

• Direct bilirubin in the liver ❌ – Seen in obstructive jaundice, not kernicterus.

• Gluconeogenesis = making glucose from non-carbohydrate precursors (important during fasting).

• Best precursors:

  • Lactate (Cori cycle).

  • Glucogenic amino acids (esp. alanine).

  • Glycerol → comes from hydrolysis of triglycerides in adipose tissue → converted into dihydroxyacetone phosphate (DHAP) → enters gluconeogenic pathway.

Now the options:

• Fructose ❌ – Already a monosaccharide that can be converted to intermediates of glycolysis, not the main gluconeogenic precursor.

• Glucose ❌ – End-product of gluconeogenesis, not its precursor.

• Galactose ❌ – Can enter glycolysis via Leloir pathway, not a major gluconeogenic precursor.

• Mannol (Mannose) ❌ – Can be converted to fructose-6-phosphate, but again, not the classic gluconeogenic substrate.

• Glycerol ✅ – Major substrate from fat breakdown, classic gluconeogenesis precursor.

• The HMP pathway (Hexose Monophosphate Shunt / Pentose Phosphate Pathway) produces NADPH + H⁺.

• NADPH is critical for maintaining reduced glutathione (GSH) in red blood cells by regenerating it from its oxidized form (GSSG) through glutathione reductase.

• Reduced glutathione protects RBCs from oxidative damage by neutralizing hydrogen peroxide and free radicals.

• Without NADPH (e.g., in G6PD deficiency), RBCs are prone to oxidative stress → hemolysis, Heinz bodies, jaundice.

Why the others are wrong

• Hemoglobin ❌ – Oxygen transport protein, not directly maintained by NADPH.

• Heme ❌ – Requires NADPH for synthesis, but the protective antioxidant role in RBCs is via glutathione.

• LDL ❌ – Lipoprotein for cholesterol transport, unrelated here.

• Glutathione ✅ – Directly depends on NADPH to stay reduced and protect RBCs.

• Bilirubin ❌ – Product of heme breakdown, not linked to NADPH protection.

• Cyanide binds to the Fe³⁺ of cytochrome a₃ in Complex IV (cytochrome oxidase) of the electron transport chain.

• This blocks the transfer of electrons to oxygen, the final electron acceptor.

• As a result:

  • The entire ETC halts.

  • No proton gradient is generated.

  • Oxidative phosphorylation stops → no ATP formed.

  • Cells undergo histotoxic hypoxia → oxygen is present in blood, but tissues cannot use it.

Why the others are wrong

• Complex I ❌ – Inhibited by rotenone, barbiturates (not cyanide).

• Carbonic anhydrase ❌ – Enzyme in RBCs/kidney for CO₂ transport, unrelated.

• Cytochrome oxidase (Complex IV) ✅ – Target of cyanide poisoning.

• ATP synthase ❌ – Inhibited by oligomycin, not cyanide.

• Complex II ❌ – Inhibited by malonate, not cyanide.

Transamination is a key process in amino acid metabolism. It involves the transfer of an amino group from an amino acid to an α-keto acid. This reaction is crucial for:

• Synthesizing non-essential amino acids

• Recycling nitrogen

• Linking amino acid metabolism to the citric acid cycle

The group that is specifically transferred in transamination is the α-amino group (α-NH₂).

For example:
Glutamate + Pyruvate → α-Ketoglutarate + Alanine
Here, glutamate donates its α-amino group to pyruvate.

This reaction is reversible and is catalyzed by enzymes known as aminotransferases (or transaminases) like ALT and AST, which are also important clinical markers of liver function.

✅ Correct Answer:

α-NH₂

❌ Why the other choices are incorrect:

• COOH / COO⁻: These are part of the amino acid backbone and not transferred during transamination.

• NH₄ (ammonium): This is involved in deamination, where the amino group is removed and released as free ammonium — not in transamination, which doesn’t produce free ammonia.

• CO₂: Released during decarboxylation, a different reaction altogether.

The liver is the body’s primary site for processing harmful substances and preparing them for excretion. One of its most vital roles is the conversion of toxic substances (like ammonia) into non-toxic or less toxic forms that can be safely eliminated from the body.

For example:

• Ammonia, which is toxic to the central nervous system, is converted by the liver into urea through the urea cycle.

• Drugs, alcohol, and other xenobiotics are transformed into more water-soluble substances so they can be excreted by the kidneys or in bile.

This overall process is known as detoxification.

✅ Correct Answer:

Detoxification

❌ Why the other options are incorrect:

• Oxidative deamination:
  This is a specific biochemical reaction that removes an amino group from an amino acid. While this contributes to nitrogen metabolism and leads to ammonia production, it is not the overall process of converting waste into excretable forms.

• Catabolic processing:
  Refers to the breakdown of molecules for energy. Although waste may be produced during catabolism, it does not directly refer to waste transformation and excretion.

• Metabolic processing:
  This is a broad, non-specific term that includes both anabolic and catabolic reactions — it doesn’t pinpoint the waste-clearing function of the liver.

• Anabolic processing:
  Refers to building complex molecules (like proteins or glycogen), not breaking down or neutralizing harmful substances.

To understand this, we need to look at how bile acids are synthesized in the body.

Bile acids are produced in the liver from cholesterol. This conversion involves a series of enzymatic reactions, primarily in hepatocytes. The two primary bile acids synthesized are:

• Cholic acid

• Chenodeoxycholic acid

These are then conjugated with taurine or glycine to form bile salts, which are more water-soluble and effective in fat digestion and absorption.

So, the key point is:

• Cholesterol → Bile acids → Bile salts

✅ Correct Answer:

Cholesterol

❌ Why the other options are incorrect:

• Taurine:
  This is used to conjugate bile acids to form bile salts, but it is not the precursor of bile acids.

• Bile salt:
  This is the product formed after conjugation of bile acids with taurine or glycine — not the precursor.

• Choline:
  This is involved in phospholipid metabolism and acetylcholine synthesis, but not in bile acid formation.

• Bile pigment:
  These are breakdown products of heme (e.g., bilirubin) and are unrelated to bile acid synthesis.

In the Krebs cycle (TCA cycle), the conversion of fumarate to malate occurs via a hydration reaction, catalyzed by the enzyme fumarase (also called fumarate hydratase).

Reaction:

Fumarate+H2O→fumaraseMalate\text{Fumarate} + \text{H}_2\text{O} \xrightarrow{\text{fumarase}} \text{Malate}Fumarate+H2​Ofumarase​Malate

• Water adds across the double bond of fumarate to produce L-malate.

• This step is essential for the subsequent oxidation of malate to oxaloacetate.

❌ Why Other Options Are Incorrect:

• CO₂: Involved in decarboxylation steps (e.g., isocitrate → α-ketoglutarate), not in the fumarate → malate step.

• Ubiquinone (Q) & Ubiquinol (QH₂): Part of the electron transport chain, not the Krebs cycle directly.

• NAD⁺: Used in the next step (malate → oxaloacetate), but not in the formation of malate.

To understand this question, let’s begin by reviewing glycogenolysis, the process by which the body breaks down glycogen into usable forms of glucose.

Glycogen is a branched polysaccharide composed of glucose units connected by α-1,4-glycosidic bonds, with α-1,6 branches. During fasting or increased energy demand, glycogen is broken down in liver and muscle cells to release glucose.

The enzyme glycogen phosphorylase plays a key role in this process. It cleaves the α-1,4 glycosidic bonds at the non-reducing ends of glycogen by using inorganic phosphate (Pi)—a process called phosphorolysis. Importantly, it does not hydrolyze glycogen (no water involved); it adds a phosphate group instead.

This reaction results in the production of glucose-1-phosphate, not free glucose or any disaccharide. This molecule is then converted by the enzyme phosphoglucomutase into glucose-6-phosphate, which can be used in glycolysis (for energy) or, in the liver, converted to free glucose by glucose-6-phosphatase for release into the bloodstream.

Now, let’s break down the options:

• Glucose-6-phosphate – ❌ Incorrect. This is the next product in the pathway, formed after glucose-1-phosphate is acted on by phosphoglucomutase. Glycogen phosphorylase doesn’t make this directly.

• Lactose – ❌ Incorrect. Lactose is a disaccharide of glucose and galactose found in milk; it’s unrelated to glycogen breakdown.

• Glucose – ❌ Incorrect. Glycogen phosphorylase does not release free glucose directly. Only debranching enzymes and hepatic glucose-6-phosphatase can ultimately lead to free glucose.

• Maltose – ❌ Incorrect. This disaccharide of glucose is produced during starch digestion (by amylase), not glycogenolysis.

• Glucose-1-phosphate – ✅ Correct. This is the direct product of glycogen phosphorylase action during glycogen breakdown.

Vitamin B6 refers to a group of chemically similar compounds: pyridoxine, pyridoxal, and pyridoxamine. These forms are converted in the liver to the biologically active form:
➡️ Pyridoxal phosphate (PLP)

PLP functions as a coenzyme in many reactions, especially those involving amino acid metabolism, such as:

• Transamination

• Decarboxylation

• Deamination

• Glycogen phosphorylase activity

Let’s go through the choices:

• Nicotinamide adenine dinucleotide (NAD) – ❌ This is the active form of niacin (vitamin B3), not B6.

• Pyridoxamine – ❌ One of the precursors of B6, but not the active form.

• Pyridoxal phosphate (PLP) – ✅ Correct. This is the active coenzyme form of vitamin B6.

• Flavin adenine dinucleotide (FAD) – ❌ This is derived from riboflavin (vitamin B2).

• Pyridoxine – ❌ A common dietary form of B6, but it requires conversion to PLP to become active.

Step 1: Recall energy concepts in biochemistry

• Exergonic reaction → A reaction that releases free energy (ΔG is negative). These are spontaneous.

• Endergonic reaction → Requires energy input (ΔG is positive). Not spontaneous.

• Oxidation / Reduction → These are electron transfer processes. Whether they release or require energy depends on the context — they’re not defined purely by energy release.

• Redox potential → A measure of the tendency of a substance to gain or lose electrons, not an actual reaction that releases energy itself.

Step 2: Analyze the options

• Endergonic reaction
  ❌ Requires energy, doesn’t release it.

• Oxidation
  ❌ Oxidation is loss of electrons; sometimes it releases energy, but not always. Too general to be the best answer.

• Reduction
  ❌ Reduction is gain of electrons; again, not necessarily tied to energy release.

• Exergonic reaction
  ✅ Correct. By definition, exergonic reactions release free energy.

• Redox potential
  ❌ A property/measure, not a reaction.

• The HMP shunt / Pentose Phosphate Pathway (PPP) occurs in the cytosol and has two phases:

  • Oxidative phase → produces NADPH.

  • Non-oxidative phase → produces ribose-5-phosphate for nucleotide synthesis.

• Glucose-6-phosphate dehydrogenase (G6PD) catalyzes the rate-limiting step:

  • Glucose-6-phosphate → 6-phosphogluconolactone.

  • This step generates NADPH, essential for fatty acid synthesis, cholesterol synthesis, and protecting RBCs against oxidative stress.

Why the other options are wrong

• Glucokinase ❌ → Liver enzyme in glycolysis; phosphorylates glucose to glucose-6-phosphate. Not specific for HMP shunt regulation.

• PEPCK ❌ → Key enzyme of gluconeogenesis (phosphoenolpyruvate carboxykinase). Not related here.

• Thiolase ❌ → Involved in fatty acid metabolism (β-oxidation, ketone body synthesis). Not part of PPP.

• Hexokinase ❌ → Ubiquitous enzyme phosphorylating glucose (glycolysis). Again, not rate-limiting in HMP shunt.

Bilirubin is produced from the breakdown of heme (mainly from senescent red blood cells). In its unconjugated form, bilirubin is water-insoluble and transported to the liver bound to albumin. To make bilirubin soluble for excretion in bile, the liver hepatocytes conjugate it with glucuronic acid.

• This reaction is catalyzed by the enzyme UDP-glucuronyl transferase.

• The product, bilirubin diglucuronide, is water-soluble and can be excreted into bile canaliculi, ultimately reaching the intestines.

• This step is crucial in preventing the toxic accumulation of unconjugated bilirubin (as seen in conditions like Crigler–Najjar syndrome or Gilbert’s syndrome).

❌ Why the Other Options Are Incorrect:

• Glycine → Conjugates with bile acids (not bilirubin).

• Glutamine → Used in nitrogen metabolism, not bilirubin conjugation.

• Acetyl-CoA → Involved in energy metabolism and fatty acid synthesis, not bilirubin processing.

• Taurine → Like glycine, conjugates with bile acids, not bilirubin.

Trypsinogen is an inactive zymogen secreted by the pancreas into the duodenum. It needs to be activated into trypsin, which then plays a central role in protein digestion and activation of other pancreatic enzymes.

• The enzyme enterokinase (enteropeptidase), secreted by the mucosal cells of the duodenum, catalyzes this activation.

• Enterokinase cleaves a specific peptide bond in trypsinogen → converting it into active trypsin.

• Once a small amount of trypsin is formed, it can autocatalytically activate more trypsinogen molecules — a positive feedback mechanism that amplifies digestion.

❌ Why the Other Options Are Wrong:

• Lipase → Breaks down fats (triglycerides → glycerol + fatty acids), no role in trypsinogen.

• Trypsinogenase → Not an actual enzyme; distractor.

• Thrombin → Blood clotting enzyme, unrelated to digestion.

• Amylase → Breaks down starch into maltose, not involved in zymogen activation.

Saturated fatty acids with 14 carbons (myristic acid) and 16 carbons (palmitic acid) are the most hypercholesterolemic among common dietary SFAs. Their principal effect is to raise plasma LDL cholesterol. Mechanistically, they tend to reduce hepatic LDL receptor activity/expression, slowing LDL clearance and thus elevating circulating LDL levels. They may also increase hepatic cholesterol availability, reinforcing the rise in LDL particles.

Let’s evaluate each option:

• Triglycerides:
  Typically rise more with refined carbohydrates, alcohol, and excess caloric intake. SFAs (especially C14:0 and C16:0) aren’t primary drivers of fasting triglyceride elevation compared with carbs or fructose.

• VLDL:
  VLDL secretion reflects hepatic triglyceride availability. While SFAs can influence liver lipid metabolism, the most consistent and pronounced change seen with myristic/palmitic intake is LDL, not VLDL.

• Low-density lipoprotein (LDL):
  Most strongly increased by myristic and palmitic acids. This is the hallmark lipid effect of these SFAs and the key reason they’re considered atherogenic in excess.

• High-density lipoprotein (HDL):
  SFAs can produce a modest rise in HDL, but the effect is smaller and less consistent than the increase in LDL. It’s not the “most potential increase.”

• Cholesterol (total):
  Total cholesterol often rises because LDL rises; however, “total cholesterol” is nonspecific. The question asks which component shows the most increase—this points specifically to LDL rather than total.

• Insulin is an anabolic hormone that decreases gluconeogenesis in the liver.

• It promotes glycogen synthesis, glycolysis, and lipid synthesis, shifting metabolism toward storage of nutrients.

• By inhibiting key gluconeogenic enzymes (e.g., PEP carboxykinase, glucose-6-phosphatase), insulin reduces glucose production.

Incorrect answer explanations:

• Cortisol → Increases gluconeogenesis by upregulating gluconeogenic enzymes.

• Glucocorticoids → Same as cortisol; stimulate gluconeogenesis.

• Glucagon → Promotes gluconeogenesis by activating PEP carboxykinase and fructose-1,6-bisphosphatase.

• Epinephrine → Increases gluconeogenesis and glycogenolysis to raise blood glucose during stress.

The major regulatory enzyme in cholesterol biosynthesis is HMG-CoA reductase. It catalyzes the rate-limiting step, converting HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) into mevalonate, a crucial precursor in the cholesterol synthesis pathway. This enzyme is tightly regulated by feedback inhibition from cholesterol and activated by insulin while inhibited by glucagon. Statins, widely prescribed lipid-lowering drugs, act by competitively inhibiting HMG-CoA reductase to decrease cholesterol levels.

Other options:

• Farnesyl-PP synthase – Incorrect: This enzyme participates later in the pathway, helping form intermediates like farnesyl pyrophosphate but is not the regulatory enzyme.

• Acetyl-CoA acetyltransferase – Incorrect: This enzyme is involved in the condensation of acetyl-CoA molecules but not in the rate-limiting regulatory step of cholesterol synthesis.

• Mevalonate kinase – Incorrect: This enzyme acts after HMG-CoA reductase in phosphorylating mevalonate but is not the key regulatory point.

• HMG-CoA synthase – Incorrect: This enzyme synthesizes HMG-CoA from acetyl-CoA and acetoacetyl-CoA but is not the rate-limiting enzyme.

In the final step of glycolysis, the enzyme pyruvate kinase catalyzes the conversion of phosphoenolpyruvate (PEP) to pyruvate, generating one molecule of ATP per molecule of PEP. This is a prime example of substrate level phosphorylation, where a high-energy phosphate group is directly transferred from a phosphorylated intermediate to ADP to produce ATP.

Key features:

• Does not require oxygen.

• Does not depend on the electron transport chain or oxidative phosphorylation.

• Occurs in both aerobic and anaerobic conditions.

Other options:

• Phosphorylation – Incorrect: This term is too general and does not specify the mechanism of ATP formation.

• Aldol condensation – Incorrect: This is a carbon-carbon bond-forming reaction, not relevant to this step of glycolysis.

• Isomerization – Incorrect: This involves rearrangement of molecules (e.g., glucose-6-phosphate ↔ fructose-6-phosphate), which is not occurring here.

• Oxidative phosphorylation – Incorrect: This occurs in the mitochondria and requires the electron transport chain, unlike this direct ATP generation step in the cytoplasm.

Von Gierke disease (Glycogen Storage Disease Type I) is caused by a deficiency of the enzyme Glucose-6-phosphatase (G6P), primarily found in the liver, kidney, and intestinal mucosa.

Pathophysiology:

• Normally, during fasting, glycogen breakdown and gluconeogenesis produce glucose-6-phosphate (G6P).

• G6Pase converts G6P → free glucose that is released into the blood.

• Deficiency means glucose is trapped in the liver as G6P, leading to:

  • Severe fasting hypoglycemia

  • Hepatomegaly (due to glycogen buildup)

  • Lactic acidosis, hyperuricemia, and hyperlipidemia

Other options:

• 6-phosphogluconolactonase (PGLS) – Incorrect: Enzyme in the pentose phosphate pathway, unrelated to glycogen breakdown.

• Glucose-6-phosphate dehydrogenase (G6PD) – Incorrect: Deficiency here causes hemolytic anemia due to impaired NADPH production, not glycogen storage disease.

• 6-Phosphogluconate dehydrogenase (6PGD) – Incorrect: Another enzyme in the pentose phosphate pathway, unrelated to glycogen metabolism.

• Phosphofructokinase (PFK) – Incorrect: Key glycolysis enzyme; deficiency leads to glycogen storage disease type VII (Tarui disease), not type I.

The rate-limiting enzyme of the urea cycle is carbamoyl phosphate synthetase I (CPS I).

• It catalyzes the reaction:

  NH3+CO2+2ATP→CarbamoylphosphateNH3​+CO2​+2ATP→Carbamoylphosphate

• It occurs in the mitochondria of liver cells.

• Activator: N-acetylglutamate.

• This enzyme is crucial for detoxification of ammonia by converting it into urea for excretion.

Why the other options are incorrect:

• Ornithine transcarbamylase (OTC):
  Important for the second step, converting carbamoyl phosphate and ornithine to citrulline, but not the rate-limiting step.

• Argininosuccinate lyase:
  Splits argininosuccinate into arginine and fumarate later in the cycle, not a regulatory step.

• Argininosuccinate synthase:
  Joins citrulline with aspartate to form argininosuccinate, but also not rate-limiting.

• Ornithine synthase:
  Not an enzyme of the urea cycle; irrelevant here.

Dietary fats — mainly triglycerides, cholesterol, and fat-soluble vitamins (A, D, E, K) — are transported as chylomicrons after digestion and absorption.

Steps of absorption and transport:

1. In the intestinal lumen, dietary fats are emulsified by bile salts and broken down into monoglycerides and free fatty acids.

2. Inside the enterocytes, these are re-esterified into triglycerides.

3. They are packaged with apolipoproteins, cholesterol, and phospholipids to form chylomicrons.

4. Chylomicrons enter the lacteals (lymphatic vessels) → thoracic duct → bloodstream.

Why the other options are incorrect:

• Micelles:
  Help in transporting lipids across the intestinal brush border but are not responsible for systemic transport.

• Free fatty acids:
  Only short-chain and medium-chain fatty acids travel freely bound to albumin, not the bulk of dietary fats.

• Cholesterol:
  A lipid component, but not the transport vehicle for fats.

• Liposomes:
  Artificial lipid vesicles used in drug delivery, not in natural fat transport.

Key point:
Chylomicrons are the primary carriers of dietary triglycerides and cholesterol from the intestine to peripheral tissues and the liver via the lymphatic and circulatory systems.

In the Krebs cycle (TCA cycle), succinate is formed from succinyl-CoA in a reaction catalyzed by succinyl-CoA synthetase (also called succinate thiokinase).

• This step generates GTP (guanosine triphosphate) via substrate-level phosphorylation.

• GTP can then be converted into ATP by nucleoside diphosphate kinase.

Option breakdown:

• NADPH – Incorrect: Not generated in the Krebs cycle; mainly produced in the pentose phosphate pathway.

• ATP – Incorrect: The immediate product is GTP, not ATP (though GTP can be converted to ATP).

• NADH – Incorrect: NADH is generated in other steps like isocitrate → α-ketoglutarate or malate → oxaloacetate, but not in succinate formation.

• GTP – Correct: Produced directly in the succinyl-CoA → succinate step.

• FADH – Incorrect: Actually FADH₂ (not FADH) is generated during the succinate → fumarate step, not during succinate formation.