Endo – Biochemistry

This question explores inborn errors of metabolism, where specific genetic defects lead to abnormal metabolic byproducts that can produce distinctive odors. Recognizing these smells is helpful for early clinical suspicion and diagnosis.

🔍 What is Methionine Malabsorption Syndrome?

• Also known as Hypermethioninemia, it involves a defect in methionine metabolism.

• Methionine is a sulfur-containing amino acid. When it’s not metabolized properly, it builds up and is converted into volatile sulfur compounds, especially dimethylsulfide.

• These compounds are excreted through breath, sweat, and urine — leading to a musty, cabbage-like odor, often described as similar to an “oast house” smell.

🏠 An “oast house” is a building used to dry hops for brewing beer, and it often smells musty and sulfurous — hence the analogy.

✅ Correct Option Explained:

✅ Methionine malabsorption syndrome

• Leads to elevated methionine and sulfurous byproducts.

• The “oast house” smell is classic and distinctive in these patients.

❌ Incorrect Options Explained:

❌ Phenylketonuria (PKU)

• Has a musty or mouse-like body odor due to phenylacetic acid.

• Not associated with a sulfurous or oast house smell.

❌ Maple syrup urine disease (MSUD)

• Has sweet-smelling urine, like burnt sugar or maple syrup, due to buildup of branched-chain ketoacids.

❌ Diabetic ketoacidosis (DKA)

• Produces a fruity or acetone-like odor in the breath due to ketone bodies.

❌ Trimethylaminuria

• Known as “fish odor syndrome”, due to accumulation of trimethylamine, giving off a strong fishy smell.

Testosterone is the mandatory branching point:

• Testosterone → Estradiol via aromatase

• Testosterone → DHT via 5-α-reductase

There is no alternate pathway that produces estradiol or DHT without first forming testosterone.

Why the other options are incorrect

❌ Cholesterol

• It is the parent precursor of all steroid hormones, but it is too upstream and not the specific common intermediate for estradiol and DHT.

❌ Estrogen

• Estradiol is an end product, not an intermediate.

❌ Pregnenolone

• An early steroid precursor; does not directly branch into estradiol and DHT.

❌ Progesterone

• Important steroid intermediate, but not obligatory for both estradiol and DHT synthesis.

Let’s walk through the thyroid hormone synthesis process like we’re assembling a custom gadget:

1. Iodide uptake: Iodide (I⁻) is actively transported from the blood into the thyroid follicular cell via the sodium-iodide symporter (NIS).

2. Oxidation: Inside the follicle, iodide is oxidized to iodine (I₂). ✅ This step requires thyroid peroxidase (TPO).

3. Organification: The oxidized iodine binds to tyrosine residues on thyroglobulin to form MIT (mono-iodotyrosine) and DIT (di-iodotyrosine). ✅ Also TPO-dependent.

4. Coupling: Two DITs combine to form T4, or one MIT + one DIT to form T3. ✅ Again, TPO catalyzes this.

So, if thyroid peroxidase is deficient, the entire series — oxidation, organification, and coupling — is impaired, preventing synthesis of T3 and T4.

❌ Why the other options are incorrect:

• Reduction and oxidation ❌
  Only oxidation of iodide is relevant here. “Reduction” is not a step in thyroid hormone synthesis.

• Binding of iodide to thyroglobulin ❌
  It’s iodine, not iodide, that binds — and this process is part of organification, not a separate independent step.

• Coupling only ❌
  TPO is involved in coupling, but also in oxidation and organification — so this choice is too narrow.

• Absorption of iodine ❌
  Iodide absorption (uptake) is carried out by the sodium-iodide symporter, not TPO.

Most lipid-soluble hormones (like steroid hormones) are made from cholesterol as a starting point.

These include:

• Estrogen ✅

• Testosterone ✅

• Glucocorticoids (like cortisol) ✅

• Progesterone ✅

They’re all steroid hormones synthesized from cholesterol via enzymatic steps in the adrenal glands or gonads.

🔴 But one stands out:

❌ Retinoic acid is not derived from cholesterol.
It comes from vitamin A (retinol), which is a dietary fat-soluble vitamin, not a steroid.

• Retinoic acid acts via intracellular receptors, similar to steroid hormones

• But biochemically, its precursor is retinol, not cholesterol

❌ Why the Other Options Are Incorrect:

• Estrogen ❌ → Derived from testosterone → comes from cholesterol

• Glucocorticoid ❌ → Synthesized from cholesterol in the adrenal cortex

• Progesterone ❌ → Directly synthesized from cholesterol → precursor for other steroids

• Testosterone ❌ → Synthesized from cholesterol via pregnenolone pathway

To understand why ferritin is not required, let’s briefly review how thyroid hormones are synthesized:

🔬 Key Components Required for Thyroid Hormone Synthesis & Secretion:

1. Iodine:

   • Actively transported into follicular cells and oxidized to iodine, which binds to tyrosine residues on thyroglobulin.

   • Essential for formation of T3 (triiodothyronine) and T4 (thyroxine).

2. Peroxidase enzyme (Thyroid peroxidase – TPO):

   • Catalyzes both the oxidation of iodide and the iodination of tyrosine, and also couples iodotyrosines (MIT + DIT) to form T3/T4.

3. Tyrosine:

   • An amino acid that provides the backbone for T3 and T4 synthesis.

4. Thyroglobulin:

   • A large glycoprotein secreted by follicular cells into the colloid, acts as a scaffold to hold iodinated tyrosines until they are cleaved and secreted as T3/T4.

🚫 Why Ferritin is NOT Necessary:

• Ferritin is a cellular iron-storage protein, unrelated to thyroid hormone synthesis.

• It stores iron in tissues and releases it when needed, but does not participate in the iodine-tyrosine-thyroglobulin process.

• Therefore, ferritin plays no direct role in the synthesis, storage, or secretion of thyroid hormones.

❌ Explanation of Incorrect Options:

• Iodine – Essential substrate for hormone production.

• Peroxidase enzyme – Required for iodide oxidation and coupling of iodotyrosines.

• Tyrosine – Base structure that gets iodinated to form MIT/DIT → T3/T4.

• Thyroglobulin – Protein scaffold that stores the hormone precursors in the colloid.

Step-by-Step Breakdown:

What happens in beta cells?

• Beta cells of the pancreas are responsible for detecting blood glucose levels and secreting insulin in response.

• For beta cells to sense glucose, glucose must enter the cell (via GLUT2 transporters) and be phosphorylated to glucose-6-phosphate.

• This phosphorylation is essential to trap glucose inside the cell and initiate its metabolism, which ultimately triggers insulin secretion.

Which enzyme phosphorylates glucose?

Two important enzymes phosphorylate glucose in different tissues:

• Glucokinase is the specific isoenzyme found in beta cells of the pancreas and hepatocytes.

• It allows beta cells to respond to rising glucose concentrations after a meal.

Why the Other Options Are Incorrect:

• 1. Glycogen phosphorylase ❌

  • Breaks down glycogen into glucose-1-phosphate — has nothing to do with initial glucose phosphorylation.

• 2. Hexokinase ❌

  • Not used in beta cells — found in tissues like muscle and brain.

• 3. Glucose kinase ❌

  • Incorrect term — not a recognized enzyme name. The correct term is glucokinase.

• 5. Insulin receptor ❌

  • Involved in insulin signaling, not in glucose metabolism or phosphorylation.

Summary:

In pancreatic beta cells, glucose is phosphorylated by glucokinase, which plays a critical role in glucose sensing and insulin secretion.

1. Role of Aldosterone:

• Aldosterone is a mineralocorticoid hormone secreted by the adrenal cortex.

• Its primary functions include:

  • Increasing sodium reabsorption in the distal tubules and collecting ducts of the kidney, which leads to water retention and helps maintain blood volume and blood pressure.

  • Promoting potassium excretion into the urine.

2. What happens in Hypoaldosteronism?

• Decreased aldosterone levels lead to:

  • Reduced sodium reabsorption → loss of sodium in urine → hyponatremia (low blood sodium) (Note: not hypernatremia).

  • Decreased potassium excretion → potassium retention → hyperkalemia (high blood potassium).

Analyzing Each Option:

Option 1: Hypokalemia (low potassium)

• Incorrect.

• Hypoaldosteronism causes the opposite — potassium builds up in the blood because less is excreted.

Option 2: Hypercalcemia (high calcium)

• Incorrect.

• Aldosterone does not have a major direct effect on calcium levels.

Option 3: Hyperlycemia (likely meant hyperglycemia)

• Incorrect.

• Aldosterone primarily affects sodium and potassium; it does not directly affect glucose metabolism.

Option 4: Hypernatremia (high sodium)

• Incorrect.

• Low aldosterone leads to sodium loss, so hyponatremia (low sodium), not hypernatremia.

Option 5: Hyperkalemia (high potassium)

• Correct.

• Hypoaldosteronism reduces potassium excretion, causing potassium to accumulate in the blood.

Summary:

Hypoaldosteronism leads to hyperkalemia due to decreased potassium excretion and hyponatremia due to sodium loss.

Management requires rapid correction of:

1. Insulin deficiency

2. Fluid loss

3. Electrolyte imbalance (especially potassium)

💊 Treatment Principles:

• Insulin therapy (IV insulin) is the cornerstone of DKA treatment to stop ketone production and reduce blood glucose.

• Fluid resuscitation (IV normal saline) to correct dehydration.

• Electrolyte correction, particularly potassium, which can drop during insulin therapy.

• Once stabilized, the patient is transitioned to subcutaneous insulin and a diabetic diet to maintain glucose control and prevent recurrence.

❌ Why other options are incorrect:

• Oral hypoglycemic drugs: 🚫 Not effective in acute DKA. They act slowly and don’t reverse ketosis.

• Low fat diet and insulin: 🚫 Fat restriction is not directly relevant in acute DKA management.

• High protein diet and insulin: 🚫 Not part of standard DKA treatment. Excess protein may worsen renal burden.

• Balanced diet and insulin: 🚫 A general term; lacks the precision of a diabetic diet, which specifically manages carbohydrate intake.

🔬 Overview of Steroid Hormone Biosynthesis:

Steroid hormones (like cortisol, aldosterone, estrogen, testosterone, etc.) are synthesized from cholesterol in a multistep pathway. The very first intermediate in this biosynthesis is:

➡️ Cholesterol → Pregnenolone
(This conversion is catalyzed by the mitochondrial enzyme cholesterol desmolase, also known as P450scc.)

Pregnenolone then serves as a precursor molecule that branches into several different steroidogenic pathways:

• Glucocorticoids (e.g., cortisol)

• Mineralocorticoids (e.g., aldosterone)

• Androgens (e.g., DHEA, testosterone)

• Estrogens (e.g., estradiol)

Thus, pregnenolone is the first committed intermediate in the synthesis of all steroid hormones.

🔍 Why the Other Options Are Incorrect:

• Prostacyclin:
  This is not a steroid hormone intermediate. It is an eicosanoid (a prostaglandin derivative), synthesized from arachidonic acid, not cholesterol.

• Progestin:
  This is a synthetic analogue of the natural hormone progesterone used in hormonal medications (like contraceptives). It’s not an intermediate in the natural biosynthetic pathway.

• Proelastase:
  This is a zymogen (inactive enzyme precursor) of elastase, an enzyme involved in protein digestion, not hormone synthesis.

• Protanope:
  This is not even related to biochemistry. A protanope refers to a person with protanopia, a type of red-green color blindness.

✅ Blood glucose levels:
Regular monitoring is essential to guide insulin infusion rates, prevent hypoglycemia, and assess the patient’s response to therapy.

Why the other options are incorrect:

❌ Glucose levels in urine:
Not reliable or helpful in acute management — urine glucose lags behind real-time blood glucose and doesn’t guide therapy.

❌ Blood insulin levels:
Not practical or useful in acute settings. Exogenous insulin is being given; measuring endogenous insulin is not relevant.

❌ Levels of ketone bodies in blood:
Useful initially for diagnosis, but not required to be monitored continuously. Blood glucose is a better indicator of therapeutic response.

❌ HbA1c:
Reflects long-term glycemic control (over 2–3 months) — not helpful in managing acute DKA.

Insulin secretion from pancreatic β-cells is a well-regulated, glucose-dependent process. It involves intricate ion channel activity, membrane potential changes, and calcium signaling. Let’s break it down step-by-step.

🔬 Mechanism of Insulin Secretion:

1. Glucose Uptake:

   • Glucose enters the β-cell via GLUT2 transporters.

2. Glucose Metabolism:

   • Inside the cell, glucose undergoes metabolism (glycolysis → ATP production).

   • Increased ATP/ADP ratio inside the cell is the key signal.

3. Closure of ATP-sensitive Potassium (K⁺) Channels:

   • The increase in ATP causes closure of these channels.

   • Potassium ions (K⁺) can no longer exit the cell → K⁺ accumulates, causing membrane depolarization.

4. Calcium Influx:

   • Depolarization opens voltage-gated Ca²⁺ channels.

   • Calcium influx triggers exocytosis of insulin-containing granules.

✅ Correct Statement:

Closure of potassium channels which leads to potassium accumulation in beta cell

• This is the essential first step leading to membrane depolarization and insulin release.

❌ Why the Other Options Are Incorrect:

• Opening of potassium channels → potassium deficiency:

  • This would hyperpolarize the membrane, preventing insulin secretion.

• Closure of both sodium and potassium channels:

  • Sodium channels are not central to insulin secretion in β-cells.

  • Potassium closure is needed; sodium involvement is minimal.

• Opening of sodium channels → sodium outflow:

  • Sodium moves into the cell, not out, and plays little role in this process.

• Closure of sodium channels → sodium accumulation:

  • Incorrect physiology — sodium does not accumulate this way, and sodium channels are not involved in insulin release.

All catecholamines — including dopamine, norepinephrine, and epinephrine — are derived from the amino acid tyrosine.

Here’s the simplified pathway:

1. Tyrosine
   ⬇ (Tyrosine hydroxylase)

2. L-DOPA
   ⬇ (DOPA decarboxylase)

3. Dopamine
   ⬇ (Dopamine β-hydroxylase)

4. Norepinephrine
   ⬇ (Phenylethanolamine-N-methyltransferase — in adrenal medulla)

5. Epinephrine

This pathway mainly occurs in sympathetic neurons and the adrenal medulla.

So, tyrosine is the starting point for all catecholamines.

❌ Why the Other Options Are Incorrect:

• Valine ❌
  Branched-chain amino acid — used in protein synthesis and energy, not in neurotransmitter synthesis.

• Arginine ❌
  Precursor for nitric oxide, urea cycle, and creatine, but not catecholamines.

• Histidine ❌
  Used to make histamine, not catecholamines.

• Tryptophan ❌
  Precursor for serotonin and melatonin, not dopamine, norepinephrine, or epinephrine.

Insulin is a peptide hormone made up of two different chains:

• The A chain (21 amino acids)

• The B chain (30 amino acids)

These two chains are linked by disulfide bonds, which hold them together. Because these chains are not identical, insulin is called a heterodimer (from hetero- meaning different, and -dimer meaning two parts).
This structure is essential for insulin’s function—without both chains, it can’t bind properly to its receptor.

❌ Why the Other Options Are Incorrect:

• Monomeric ❌
  Sounds tempting—but a monomer is a single chain, and insulin has two.

• Polymeric ❌
  That would mean many repeating units, like in DNA or plastics. Insulin is only two chains—not a polymer.

• Homodimer ❌
  A homodimer is two identical chains. Insulin has two different chains—so no match here.

• Tertiary ❌
  That describes the 3D folding of one chain. Insulin has two chains, so this is incomplete.

Glucocorticoids (like cortisol, or synthetic ones like prednisone) are powerful anti-inflammatory hormones. Their primary action is to suppress the immune system and inhibit inflammation at its source.

They act upstream in the arachidonic acid pathway — a critical cascade involved in producing pro-inflammatory mediators like:

• Prostaglandins (via COX enzymes)

• Leukotrienes (via lipoxygenase enzymes)

🧪 Phospholipase A₂ – the Critical Enzyme:

• Phospholipase A₂ (PLA₂) is the enzyme that liberates arachidonic acid from phospholipids in the cell membrane.

• Once free, arachidonic acid becomes the substrate for:

  • Cyclooxygenase (COX) → prostaglandins, thromboxanes

  • 5-lipoxygenase → leukotrienes

📌 Glucocorticoids inhibit PLA₂ by increasing production of lipocortin (annexin-1), a protein that suppresses PLA₂ activity.
→ This stops both branches of the pathway before they begin.

❌ Why the Other Options Are Incorrect:

❌ Histidine decarboxylase

• Converts histidine → histamine

• Plays a role in allergic responses

• Not part of the arachidonic acid or glucocorticoid pathways

❌ Xanthine oxidase

• Involved in purine metabolism → forms uric acid

• Target of allopurinol (used in gout)

• Not regulated by glucocorticoids

❌ Cyclooxygenase (COX)

• Converts arachidonic acid to prostaglandins and thromboxanes

• NSAIDs (like ibuprofen) directly inhibit COX enzymes

• Glucocorticoids inhibit PLA₂ upstream, so COX activity is indirectly reduced, not directly inhibited

❌ 5-lipoxygenase

• Converts arachidonic acid to leukotrienes

• Leukotriene inhibitors (e.g. zileuton) target this enzyme

• Again, glucocorticoids don’t inhibit this directly — they prevent its substrate (arachidonic acid) from forming

The thyroid gland makes T₃ (triiodothyronine) and T₄ (thyroxine), and for that, it needs iodine in a specific active form.

Here’s how it works step-by-step:

1. Iodide ions (I⁻) are absorbed from the blood into thyroid follicular cells.

2. These iodide ions must first be oxidized to elemental iodine (I⁰) by the enzyme thyroid peroxidase (TPO).

3. Only oxidized iodine can attach to tyrosine residues on thyroglobulin to form:

   • MIT (mono-iodotyrosine)

   • DIT (di-iodotyrosine)
     → Which then combine to form T₃ and T₄

✅ So the oxidation of iodide to iodine is an essential and rate-limiting step in thyroid hormone formation.

❌ Why the Other Options Are Wrong (Simple):

• Thyroxine

  • This is the final product (T₄), not a step in the formation process.

• Iodide to chloride

  • ❌ Not part of thyroid hormone synthesis. This reaction doesn’t happen.

• Thyroglobulin

  • Yes, it’s important, as the scaffold for hormone formation — but the oxidation of iodide must occur before iodination of thyroglobulin.

• Iodide to sodium iodide

  • Sodium iodide is how iodide is absorbed from the gut, not how it’s activated in the thyroid.

Insulin is a protein hormone made by β-cells of the pancreas and plays a key role in lowering blood glucose levels.

Its mature, active form consists of:

• Two separate chains:

  • A (alpha) chain = 21 amino acids

  • B (beta) chain = 30 amino acids

• These chains are connected by two disulfide bonds (and one intrachain disulfide bond in the A chain).

Together, the total is 51 amino acids — but the structure is not one continuous chain, it is two separate chains held together by bonds.

This structure forms after processing of preproinsulin inside the β-cell:

1. Preproinsulin → 108 amino acids (includes signal sequence)

2. Proinsulin → 86 amino acids (after signal is cleaved)

3. Insulin → final hormone with A and B chains + C-peptide is removed

❌ Why the Other Options Are Wrong (Simple):

• Preproinsulin having 108 amino acids and proinsulin having 86 amino acids

  • ✅ This is true about the precursors, but the question is asking about the final composition of insulin.

• A single polypeptide chain of 84 amino acids

  • ❌ Incorrect — insulin is two chains, not one.

• An α chain having 108 amino acids and a β chain having 30 amino acids

  • ❌ Wrong — no such structure exists. 108 is the preproinsulin total, not a single chain.

• A single polypeptide chain of 51 amino acids

  • ❌ Insulin has 51 amino acids total, yes — but it is not a single chain, it’s two chains joined by disulfide bonds.

In Type 1 Diabetes Mellitus, the body doesn’t make insulin (due to autoimmune destruction of pancreatic beta cells).

Insulin normally suppresses gluconeogenesis, which is the process where the liver produces new glucose from non-carbohydrate sources (like amino acids and glycerol).

So in the absence of insulin:

• The liver keeps making glucose, even when there’s already too much in the blood.

• This leads to increased gluconeogenesis, making hyperglycemia worse.

This is one of the most prominent metabolic changes in T1DM.

❌ Why the Other Options Are Wrong (Simple):

• Decreased lipolysis
  ❌ Incorrect — in fact, lipolysis increases in T1DM due to lack of insulin. Fat is broken down for energy.

• Increased lipogenesis
  ❌ Wrong — lipogenesis (fat creation) requires insulin. In T1DM, lipogenesis is reduced, not increased.

• None of these
  ❌ Incorrect — one of the changes is clearly true, and that’s increased gluconeogenesis.

• Decreased ketogenesis
  ❌ Incorrect — ketogenesis increases in T1DM due to unopposed fat breakdown, leading to ketoacidosis.

Insulin is a protein hormone that helps control blood sugar levels.

Structurally, insulin is made up of two different chains:

• A chain (21 amino acids)

• B chain (30 amino acids)

These two chains are linked together by disulfide bonds.

Since insulin is made of two different chains that come together to work as one unit, we call it a heterodimer:

• Hetero = different

• Dimer = two units

So, heterodimer means it has two different parts working together, which fits insulin perfectly.

❌ Why the Other Options Are Wrong (Simple):

• Tertiary – This refers to the 3D folding of a single protein chain, not to how insulin is structured as two chains joined together.

• Polymeric – Means many repeating units (like plastics or starch). Insulin is not made of repeating subunits, so it’s not a polymer.

• Monomeric – A monomer is a single unit, but insulin has two chains, so it’s not a monomer.

• Homodimer – That means two identical chains working together. Insulin’s two chains (A and B) are different, so it’s not a homodimer.

All steroids share a common cyclopentanoperhydrophenanthrene ring structure, which consists of:

• 3 six-membered rings (A, B, C)

• 1 five-membered ring (D)

This 4-ring carbon skeleton is the signature feature of all steroids, including:

• Cholesterol

• Cortisol

• Testosterone

• Estrogen

• Aldosterone

• Progesterone

• Vitamin D (modified steroid structure)

❌ Why the Other Options Are Incorrect:

• At least 1 fatty acid
  ❌ Steroids are not fatty acids or triglycerides — they are lipid-derived but do not contain fatty acid chains.

• Glycerol group
  ❌ Found in triglycerides and phospholipids, not in steroid structures.

• Soluble in water
  ❌ Steroids are lipophilic, not water-soluble — they need carrier proteins in the bloodstream.

• Made in liver
  ❌ Not all — for example, cortisol and aldosterone are made in the adrenal cortex, sex steroids in gonads. The liver metabolizes them but doesn’t synthesize all of them.

A patient with:

• High ACTH

• Low cortisol

• Elevated 11-deoxycorticosterone (DOC)

…points to 11β-hydroxylase deficiency.

🧪 Biochemical Pathway:

Normally:

• 11-deoxycorticosterone (DOC) → Corticosterone via 11β-hydroxylase

• 11-deoxycortisol → Cortisol via 11β-hydroxylase

When 11β-hydroxylase is deficient:

• DOC and 11-deoxycortisol accumulate

• Cortisol and corticosterone are low

• Low cortisol → ↑ ACTH via negative feedback

• DOC (a mineralocorticoid) builds up → hypertension (not salt-wasting)

❌ Why Others Are Wrong:

• 21-hydroxylase deficiency → ↓ DOC, ↓ aldosterone, ↓ cortisol → salt-wasting, not elevated DOC

• 17α-hydroxylase deficiency → ↓ sex steroids and cortisol, ↑ DOC and aldosterone, but ambiguous genitalia and low androgens are more prominent

• 18α-hydroxylase → not classically involved in congenital adrenal hyperplasia (CAH)

• CYP → too vague (refers to cytochrome P450 enzymes broadly)

Reference : https://www.wikidoc.org/index.php/11%CE%B2-hydroxylase_deficiency_pathophysiology

🔹 Timeline of Fasting Metabolism

When food intake stops, the body switches through several stages of fuel use:

1. 0–24 hours (Early fasting)

   • Primary energy source: Glycogenolysis (liver glycogen → glucose)

   • Fat breakdown starts slowly.

2. 1–3 days (Short-term fasting)

   • Liver glycogen stores are depleted (~24 hrs).

   • Gluconeogenesis becomes the main source of blood glucose (from amino acids, glycerol, lactate).

   • Lipolysis increases to provide fatty acids.

3. >3–5 days (Prolonged fasting/starvation)

   • Brain adapts to using ketone bodies (β-hydroxybutyrate, acetoacetate) to spare protein breakdown.

   • Ketogenesis in the liver becomes the main energy source for the brain and much of the body.

   • Lipolysis fuels ketogenesis.

🔹 Why Ketogenesis Is Correct Here

• After one week without food, the primary energy supply for most tissues, especially the brain, comes from ketone bodies.

• This adaptation reduces protein degradation, preserving muscle mass.

• Gluconeogenesis continues at a low rate for tissues that must have glucose (RBCs, renal medulla), but it’s not the primary energy source at this point.

❌ Why the Other Options Are Wrong:

• Glycogenolysis → Only lasts about 24 hours; long gone by one week.

• Gluconeogenesis → Still occurs but is secondary; ketones have taken over most of the energy supply.

• Protein degradation → Reduced during prolonged starvation to spare muscle; not the main energy source now.

• Lipolysis → Still ongoing, but fatty acids from lipolysis are mainly used by muscle; the primary energy source overall is ketones derived from this fat.

There are three ketone bodies, but not all are ketones chemically or detectable in urine:

➡️ Acetoacetate is the only major ketone body that:

• Is a true ketone

• Is detectable in urine with common clinical dipstick tests (like nitroprusside reaction)

Beta-hydroxybutyrate is the most abundant in DKA, but cannot be detected by urine dipsticks — blood-specific tests are required for that.

❌ Why the Other Options Are Incorrect:

• Acetone
  ❌ Volatile and exhaled through lungs — not excreted significantly in urine.

• Beta-hydroxybutyric acid
  ❌ Technically not a ketone (no ketone group) and not detected on standard urine tests.

• Acetaldehyde
  ❌ Byproduct of alcohol metabolism — not a ketone body.

• Acetoacetyl-CoA
  ❌ A fatty acid intermediate — too large to be excreted in urine and not a circulating ketone body.

Amine hormones are derived from one of two amino acids:

• Tyrosine → gives rise to:

  • Dopamine ✅

  • Norepinephrine

  • Epinephrine

  • Thyroid hormones (T₃/T₄)

• Tryptophan → gives rise to:

  • Serotonin

  • Melatonin

So, dopamine is a catecholamine, and it is the first product in the tyrosine → dopamine → norepinephrine → epinephrine pathway.

❌ Why the Other Options Are Incorrect:

• Bradykinin
  ❌ It’s a peptide, not an amine, and is not derived from tyrosine.

• Serotonin
  ❌ Derived from tryptophan, not tyrosine.

• Histamine
  ❌ Derived from histidine, not tyrosine.

• Melatonin
  ❌ Also derived from tryptophan → via serotonin, not tyrosine.

The HbA1c test (also called glycated hemoglobin or A1c) reflects the average blood glucose levels over the past 2–3 months. This is because glucose molecules slowly attach to hemoglobin in red blood cells. Since red blood cells live for about 120 days, the HbA1c gives a long-term picture of glucose control.

It’s a key diagnostic and monitoring tool for diabetes mellitus and is more stable than a single fasting or random glucose measurement.

❌ Why the Other Options Are Incorrect:

• Random blood glucose test ❌
  Measures sugar levels at a single moment, not over a period of time.

• Hemoglobin ❌
  Measures red blood cell count or oxygen-carrying capacity, not glucose control.

• Fasting blood sugar test ❌
  Measures blood glucose after 8 hours of fasting. Only reflects glucose at one point in time.

• Glucose tolerance test ❌
  Used to assess how the body handles a glucose load, mostly for diagnosing diabetes or gestational diabetes—not for long-term glucose levels.

Insulin is an anabolic hormone—it promotes storage of nutrients (like glucose and fat) and inhibits catabolic pathways (breakdown of stored fuels). One of the key enzymes inhibited by insulin is hormone-sensitive lipase (HSL).

• HSL breaks down triglycerides stored in adipose tissue, releasing free fatty acids into the bloodstream.

• Insulin inhibits HSL to prevent unnecessary lipolysis during the fed state, when energy and nutrients are abundant.

This action helps the body store fat instead of breaking it down.

❌ Why the Other Options Are Incorrect:

• Glucokinase: Stimulated by insulin; promotes glucose phosphorylation in the liver.

• Glycogen synthetase: Also stimulated by insulin; promotes glycogen storage.

• Phosphofructokinase: A key glycolytic enzyme that is activated by insulin.

• Acetyl Co-A carboxylase: Involved in fatty acid synthesis and stimulated by insulin.

Zinc ions are essential for the storage and crystallization of insulin in the secretory granules of pancreatic beta cells.

• Insulin is synthesized as proinsulin, which is cleaved to form insulin + C-peptide.

• In the Golgi apparatus, insulin molecules aggregate around zinc ions, forming hexamers.

• These insulin-zinc hexamers are stable crystalline structures stored in vesicles until they are released by exocytosis in response to high blood glucose.

Zinc not only stabilizes insulin for storage but also plays a role in regulating its secretion and biological activity.

❌ Why the Other Options Are Incorrect:

• Manganate ion: Not physiologically involved in insulin storage.

• Magnesium ion: Important for ATP-dependent reactions, but not for insulin crystallization.

• Potassium ion: Involved in membrane potential and insulin release, but not insulin storage.

• Sodium ion: Involved in electrolyte balance, not in insulin packaging or crystallization.

In the absence of insulin, such as in fasting states or uncontrolled diabetes mellitus, the body shifts from using glucose to using fats for energy. This leads to increased lipolysis, releasing free fatty acids from adipose tissue. These fatty acids are then transported to the liver, where they undergo β-oxidation, producing acetyl-CoA, which is converted into ketone bodies.

This process is called ketogenesis, and it:

• Provides an alternative energy source, especially for the brain during prolonged fasting

• Can lead to ketoacidosis in insulin-deficient states like type 1 diabetes

❌ Why the Other Options Are Incorrect:

• Amino acid uptake: Stimulated by insulin; inhibited in its absence

• Glycogenesis: Requires insulin; not activated without it

• Shift of potassium into cells: Insulin promotes this—in its absence, K⁺ tends to remain in ECF, possibly leading to hyperkalemia

• Glucose uptake and utilization: Insulin is necessary for glucose uptake in muscle and fat via GLUT-4; without insulin, this process is impaired

Glucagon is a peptide hormone secreted by pancreatic alpha cells in response to low blood glucose. It primarily targets hepatocytes (liver cells) to increase blood glucose levels by stimulating:

• Glycogenolysis (breakdown of glycogen)

• Gluconeogenesis (formation of new glucose)

Glucagon binds to a G-protein-coupled receptor on hepatocyte membranes, which activates adenylyl cyclase. This enzyme converts ATP into cyclic AMP (cAMP).

cAMP then acts as a second messenger, activating protein kinase A (PKA), which initiates a phosphorylation cascade leading to increased glucose production and release.

❌ Why the Other Options Are Incorrect:

• Cyclic ATP: Does not exist—ATP is the substrate, not the second messenger.

• Phosphodiesterase: Breaks down cAMP; inhibits the signal, not activates it.

• Inositol trisphosphate (IP₃): Used by other hormones like ADH (via V1 receptors), not glucagon.

• Cyclic GMP (cGMP): Used in nitric oxide and ANP signaling, not involved in glucagon action.

Glucocorticoids (like cortisol) are catabolic hormones that mobilize energy sources during stress and fasting. One of their key actions is on protein metabolism, where they:

• Stimulate protein breakdown in muscle and other tissues

• Release amino acids into the bloodstream

These amino acids are transported to the liver, where they are used for gluconeogenesis—the production of new glucose from non-carbohydrate sources. This process helps maintain blood glucose levels, especially during fasting, stress, or prolonged illness.

❌ Why the Other Options Are Incorrect:

• Ketogenesis: Involves fatty acids and occurs in the liver, not primarily driven by amino acids.

• Glycolysis: Breaks down glucose for energy—amino acids are not involved in this process.

• Protein synthesis: Glucocorticoids actually inhibit protein synthesis; they promote protein breakdown.

• Glycogenolysis: Involves breakdown of stored glycogen, not amino acids.

Most peptide and protein hormones (like FSH, LH, glucagon, and calcitonin) exert their effects via membrane-bound receptors and use second messengers like cyclic AMP (cAMP) to relay the signal inside the cell.

However, estrogen is a steroid hormone. Steroid hormones are lipophilic, so they diffuse through the cell membrane and bind to intracellular (nuclear) receptors, not membrane-bound ones. These hormone-receptor complexes then act directly on DNA, modifying gene transcription—no second messenger like cAMP is involved.

❌ Why the Other Options Are Incorrect:

• FSH: Uses cAMP via G-protein-coupled receptors to stimulate follicular development.

• Glucagon: Activates adenylyl cyclase → cAMP → activates PKA in liver for glycogen breakdown.

• LH: Like FSH, it uses cAMP signaling in gonadal cells.

• Calcitonin: Binds to a receptor that stimulates cAMP production to inhibit bone resorption.

Glucagon is a peptide hormone secreted by pancreatic alpha cells, primarily in response to low blood glucose levels. Its main target is the liver, where it stimulates processes like glycogenolysis and gluconeogenesis to raise blood glucose.

Glucagon exerts its effects through a G-protein-coupled receptor (GPCR) on the hepatocyte membrane. This activates the adenylyl cyclase enzyme, which converts ATP into cyclic AMP (cAMP)—the key second messenger.

cAMP then activates protein kinase A (PKA), which phosphorylates enzymes that:

• Stimulate glycogen breakdown

• Promote glucose production

• Inhibit glycogen synthesis

❌ Why the Other Options Are Incorrect:

• Nuclear receptors: Used by steroid or thyroid hormones, not peptide hormones like glucagon.

• cIMP: Not a recognized or physiologically relevant second messenger.

• DNA receptors: Hormones don’t act directly on DNA receptors—this is an inaccurate term.

• cGMP: Another second messenger, but not the one used by glucagon. It’s used by nitric oxide and atrial natriuretic peptide (ANP), not glucagon.

During glycogenolysis, the enzyme glycogen phosphorylase is responsible for cleaving glucose residues from the non-reducing (peripheral) ends of glycogen chains. It removes one glucose unit at a time by breaking α-1,4 glycosidic bonds, releasing glucose-1-phosphate.

This is the first and rate-limiting step in glycogen breakdown, and it continues until glycogen phosphorylase reaches about four glucose residues away from a branch point.

❌ Why the Other Options Are Incorrect:

• Glucose-6-phosphatase: Converts glucose-6-phosphate to free glucose in the liver, not involved in the initial step of glycogen breakdown.

• Branching enzyme: Involved in glycogenesis, not glycogenolysis. It adds α-1,6 branches, not cleaves.

• Debranching enzyme: Helps remove branch points after glycogen phosphorylase has done its job, but it doesn’t release glucose-1-phosphate.

• Glycogen synthase: Responsible for building glycogen, not breaking it down.

All steroid hormones — including glucocorticoids (e.g., cortisol), mineralocorticoids (e.g., aldosterone), and sex hormones (e.g., estrogen, testosterone) — are synthesized from a single universal precursor: cholesterol.

Why Cholesterol?

• Cholesterol provides the steroid nucleus (a 4-ring structure) that is the foundation of all steroid hormones.

• In the mitochondria of steroidogenic cells, cholesterol is converted by the enzyme cholesterol desmolase (also called CYP11A1 or side-chain cleavage enzyme) into pregnenolone, the first intermediate in steroidogenesis.

Pathway Summary:

1. Cholesterol
   ↓ (via desmolase)

2. Pregnenolone
   ↓

3. Progesterone, cortisol, aldosterone, testosterone, estrogen, etc.

Thus, cholesterol is the earliest and most fundamental precursor of all steroid hormones.

Incorrect Answer Explanations:

Valine

• Valine is a branched-chain amino acid (BCAA).

• It plays a role in protein synthesis and energy metabolism, not steroid hormone synthesis.

Estrogen

• Estrogen is a final product, not a precursor.

• It is synthesized from androgens (like testosterone), which in turn are made from pregnenolone and cholesterol.

Pregnanediol

• Pregnanediol is a metabolite of progesterone, found in urine.

• It is not a precursor, but a breakdown product, often used as a marker of progesterone levels.

Pregnenolone

• Pregnenolone is an early intermediate in the pathway, produced from cholesterol.

• It is not the original precursor—that role belongs to cholesterol.

The synthesis of catecholamines (dopamine, norepinephrine, epinephrine) follows a stepwise enzymatic pathway, primarily taking place in the adrenal medulla and certain neurons.

Here’s the simplified pathway:

1. Tyrosine → (via Tyrosine hydroxylase) →

2. DOPA → (via DOPA decarboxylase) →

3. Dopamine → (via Dopamine β-hydroxylase) →

4. Norepinephrine → (via Phenylethanolamine N-methyltransferase, or PNMT) →

5. Epinephrine

The final step, converting norepinephrine to epinephrine, is catalyzed by PNMT. This enzyme adds a methyl group to norepinephrine, forming epinephrine. Importantly, PNMT activity is stimulated by cortisol, which comes from the nearby adrenal cortex—showing how the adrenal medulla and cortex function in coordination.

❌ Why the Other Options Are Incorrect:

• Monoamine oxidase (MAO): ❌ Breaks down catecholamines; it’s involved in degradation, not synthesis.

• DOPA hydroxylase: ❌ There’s no such enzyme. The correct early enzyme is tyrosine hydroxylase, which forms DOPA.

• Catechol-O-methyltransferase (COMT): ❌ Also involved in breaking down catecholamines, not synthesizing them.

• Tyrosine hydroxylase: ❌ This enzyme acts at the start of the pathway—converting tyrosine to DOPA, not norepinephrine to epinephrine.

During starvation, the body shifts into a catabolic state to maintain blood glucose and provide energy. The sequence of changes includes:

1. Early fasting (first 24 hours):

   • Liver glycogen is broken down to maintain blood glucose.

   • Glycogen stores are depleted within ~24 hours.

2. Prolonged fasting/starvation:

   • Gluconeogenesis (from amino acids, lactate, glycerol) takes over.

   • Ketone bodies increase to fuel the brain.

   • Glucagon, epinephrine, and norepinephrine all rise to mobilize energy reserves.

Thus, glycogen levels decrease, not increase.

❌ Why the Other Options Are Correctly Increased

• Glucagon
  Increases to stimulate glycogenolysis and gluconeogenesis.

• Epinephrine
  Enhances lipolysis and supports glucose production during stress.

• Norepinephrine
  Supports sympathetic responses and promotes fat breakdown.

• Ketone bodies
  Increase significantly after 2–3 days of fasting to supply energy to the brain and muscles.

This patient has mild fasting hyperglycemia that was first noticed during pregnancy (gestational diabetes) and has persisted postpartum. Her glucose is elevated but not diabetic-range, and it’s well-controlled with diet alone — this suggests a genetic form of mild hyperglycemia, most likely MODY (Maturity-Onset Diabetes of the Young) type 2, caused by glucokinase (GCK) deficiency.

Glucokinase acts as the glucose sensor in pancreatic β-cells. It catalyzes the phosphorylation of glucose to glucose-6-phosphate — the first step in glycolysis. Its reduced activity raises the threshold at which β-cells secrete insulin, so patients have mild fasting hyperglycemia, especially during metabolic stress (like pregnancy), but usually don’t develop severe diabetes.

❌ Why the Other Options Are Incorrect

• Lactate dehydrogenase
  Converts pyruvate to lactate — not involved in glucose sensing or regulation of insulin release.

• Enolase
  Converts 2-phosphoglycerate to phosphoenolpyruvate — a late glycolytic step, not rate-limiting or regulatory.

• Phosphofructokinase (PFK)
  Rate-limiting enzyme in glycolysis, but not involved in pancreatic glucose sensing. Its defect would affect energy metabolism broadly, not cause isolated hyperglycemia.

• Pyruvate kinase
  Catalyzes final step in glycolysis; deficiency leads to hemolytic anemia, not hyperglycemia.

• Glycogenolysis is the process of breaking down glycogen into glucose-1-phosphate for energy production.

• It starts at the non-reducing ends of glycogen, removing glucose residues one at a time.

Role of Glycogen Phosphorylase:

• Glycogen phosphorylase cleaves α-1,4 glycosidic bonds at the peripheral (non-reducing) ends of glycogen.

• It uses inorganic phosphate (Pi) to release glucose-1-phosphate.

• This is the rate-limiting step of glycogenolysis.

What Happens to Branches?

• When glycogen phosphorylase gets close to a branch point, it cannot cleave α-1,6 linkages.

• At that point, the debranching enzyme takes over to handle branch points.

Why the Other Options Are Incorrect:

Summary:

Glycogen phosphorylase is responsible for cleaving glucose-1-phosphate from the peripheral ends of glycogen during glycogenolysis.

• Adenylate cyclase is a membrane-bound enzyme that plays a central role in the cAMP second messenger system.

• It is activated by Gs proteins when certain hormones or neurotransmitters bind to their receptors.

• It catalyzes the conversion of ATP to cyclic AMP (cAMP).

Reaction:

ATP→cAMP+PPi (pyrophosphate)ATP→cAMP+PPi (pyrophosphate)

Function of cAMP:

• cAMP activates protein kinase A (PKA)

• PKA phosphorylates various enzymes, leading to cellular responses such as:

  • Glycogen breakdown

  • Increased heart rate

  • Hormone secretion regulation

Why the Other Options Are Incorrect:

Summary:

Adenylate cyclase converts ATP into cAMP, which serves as a second messenger in many hormone signaling pathways.

The catecholamines include:

• Dopamine

• Norepinephrine (noradrenaline)

• Epinephrine (adrenaline)

All are synthesized from Tyrosine, which is the direct precursor.

Steps in Catecholamine Synthesis:

1. Tyrosine → L-DOPA
   (enzyme: tyrosine hydroxylase; rate-limiting step)

2. L-DOPA → Dopamine

3. Dopamine → Norepinephrine

4. Norepinephrine → Epinephrine
   (in the adrenal medulla, using phenylethanolamine-N-methyltransferase, stimulated by cortisol)

Why the Other Options Are Incorrect:

Summary:

Tyrosine is the precursor of catecholamines, making it the correct answer.

The absorption of glucose from the intestine requires the breakdown of complex carbohydrates (like starch and disaccharides) into monosaccharides (glucose, galactose, fructose).

Role of Alpha-Glucosidase:

• Alpha-glucosidase is an enzyme located on the brush border of the small intestine (enterocytes).

• It breaks down oligosaccharides and disaccharides into glucose, which can then be absorbed by intestinal transporters (like SGLT1).

• Without this step, glucose cannot be absorbed, even if large carbohydrate molecules are present.

Clinical Relevance:

• Alpha-glucosidase inhibitors (e.g., acarbose, miglitol) are used to treat diabetes mellitus because they slow carbohydrate digestion, reducing postprandial blood glucose spikes.

Why the Other Options Are Incorrect:

Summary:

Alpha-glucosidase is the enzyme responsible for breaking down carbohydrates into glucose for absorption in the intestine, making it the correct answer.

1α-hydroxylase is the renal enzyme that converts 25-hydroxyvitamin D into its active form: 1,25-dihydroxyvitamin D (calcitriol).

Calcitriol increases calcium absorption from the intestine. So when 1α-hydroxylase is deficient:

• Less calcitriol →

• Less calcium absorption from the gut →

• Hypocalcemia →

• Parathyroid glands respond by secreting more PTH →
  → Secondary hyperparathyroidism (i.e., PTH increase secondary to hypocalcemia)

This is commonly seen in chronic kidney disease, where 1α-hydroxylase activity is reduced.

5) Answer Breakdown:

• 21α-hydroxylase deficiency – ❌ Affects adrenal steroid synthesis, not calcium metabolism.

• 1α-hydroxylase deficiency – ✅ Leads to low calcitriol → hypocalcemia → ↑PTH

• Deficiency of both enzymes – ❌ Only 1α-hydroxylase is relevant here

• 17α-hydroxylase deficiency – ❌ Also adrenal; leads to cortisol/sex steroid issues

• 1α-hydroxylase overexpression – ❌ Would cause hypercalcemia, not PTH elevation

Insulin is a peptide hormone composed of two polypeptide chains:

• A-chain (21 amino acids)

• B-chain (30 amino acids)

These are linked together by two disulfide bonds, and an additional intra-chain disulfide bond is present within the A-chain. Since the two chains are different, this makes insulin a heterodimeric protein (i.e., a protein made of two different subunits).

It’s not a glycolipid, amino acid, homodimer, or steroid. Steroid hormones are derived from cholesterol and are lipophilic, unlike peptide hormones like insulin.

5) Answer Breakdown:

• It is a heterodimeric protein – ✅ Correct; two different chains (A and B)

• It is a glycolipid – ❌ Insulin is a protein, not lipid-based

• It is an amino acid – ❌ It is made of amino acids but is not a single one

• It is a homodimeric protein – ❌ Wrong; A and B chains are different

• It is a steroid hormone – ❌ Peptide hormone, not steroid (not derived from cholesterol)

Cholesterol is the universal precursor for all steroid hormones. It is taken up by steroidogenic cells (like those in the adrenal cortex or gonads) and converted into pregnenolone by the enzyme cholesterol desmolase (CYP11A1) in the mitochondria. Pregnenolone then serves as the branching point for the synthesis of various steroid hormones like glucocorticoids, mineralocorticoids, and sex hormones.

While pregnenolone and pregnanediol are important intermediates in the pathway, only cholesterol is the original source molecule. Amino acids like valine are unrelated to this pathway.

5) Answer Breakdown:

• Valine – Amino acid; unrelated to steroid synthesis.

• Cholesterol – ✅ Correct. It’s the base precursor for all steroid hormones.

• Pregnanediol – A metabolite of progesterone, not a precursor.

• Estrogen – A steroid hormone itself, not a precursor.

• Pregnenolone – First product after cholesterol, but not the initial precursor.

Somatostatin is a regulatory hormone found in both the hypothalamus and the pancreas. It exists in two main forms:

• SS-14 (14 amino acids) — predominant in the pancreas

• SS-28 (28 amino acids) — more common in the gastrointestinal tract and hypothalamus

In the pancreas, somatostatin is secreted by the delta (δ) cells of the islets of Langerhans. It acts locally to inhibit:

• Insulin secretion from beta cells

• Glucagon secretion from alpha cells

• Pancreatic enzyme and bicarbonate secretion

It’s a paracrine hormone, meaning it influences nearby cells.

🧠 Answer Breakdown:

• Somatostatin ✅
  → Correct. 14-amino-acid form in the pancreas; inhibits other pancreatic hormones.

• Cortisol ❌
  → A steroid hormone, not a polypeptide; secreted by adrenal cortex.

• Insulin ❌
  → A 51-amino-acid polypeptide; not 14.

• Glucagon ❌
  → A 29-amino-acid polypeptide.

• Pancreatic polypeptide ❌
  → Composed of 36 amino acids, secreted by PP cells.

The first step in thyroid hormone synthesis is iodide trapping, also called iodide uptake. This process involves actively transporting iodide ions (I⁻) from the bloodstream into the follicular cells of the thyroid gland using a sodium-iodide symporter (NIS).

Only after iodide is trapped inside the follicular cell can it be:

1. Oxidized to iodine (I₂)

2. Organified (attached to tyrosine residues on thyroglobulin)

3. Coupled to form T₃ and T₄

4. Stored, then later released

🧠 Answer Breakdown:

• Iodide trapping ✅
  → Correct. This is the essential first step.

• Organification ❌
  → Occurs after iodide is oxidized to iodine.

• Splitting ❌
  → This refers to the breakdown of T₄ or T₃, not part of synthesis.

• Conjugation ❌
  → Refers to coupling of iodinated tyrosines (MIT + DIT) — a later step.

• Deiodination ❌
  → Happens in peripheral tissues for recycling iodine or converting T₄ to T₃.

C-peptide and insulin are both produced in equal amounts during the cleavage of proinsulin in pancreatic β-cells.

• Proinsulin → cleaved in the Golgi apparatus → Insulin + C-peptide (in equimolar amounts)

• Both are stored in secretory granules and released together in response to glucose stimulation.

🔍 Why 1:1 is correct:

• Each molecule of proinsulin yields one molecule of insulin and one molecule of C-peptide.

• Hence, the molar ratio in secretion is 1:1.

❌ Incorrect Options Explained:

• 3:1, 2:1, 1:2, 1:3 — These ratios are not physiologically accurate.
  While insulin may be degraded faster in circulation, at the point of secretion, both are released equally.

📌 Clinical Relevance:

• C-peptide is used to assess endogenous insulin production, especially in patients receiving exogenous insulin (which lacks C-peptide).

• In Type 1 diabetes, C-peptide is low or absent.

• In insulinomas, C-peptide levels are elevated along with insulin.

To answer this accurately, you must understand the biosynthetic pathway of catecholamines, which are derived from tyrosine.

Here’s the step-by-step process of catecholamine synthesis:

1. Tyrosine → DOPA
   🔹 Enzyme: Tyrosine hydroxylase
   🔹 Rate-limiting step
   🔹 Requires tetrahydrobiopterin (BH4)

2. DOPA → Dopamine
   🔹 Enzyme: DOPA decarboxylase
   🔹 Requires Vitamin B6 (pyridoxal phosphate)

3. Dopamine → Norepinephrine
   🔹 Enzyme: Dopamine β-hydroxylase
   🔹 Requires Vitamin C (ascorbic acid)

4. Norepinephrine → Epinephrine
   🔹 Enzyme: Phenylethanolamine N-methyltransferase (PNMT)
   🔹 Requires SAM (S-adenosyl methionine) as methyl donor
   🔹 Stimulated by cortisol — released from the adrenal cortex

This final step occurs primarily in the adrenal medulla, where the high local concentration of cortisol from the nearby adrenal cortex induces PNMT activity.

Why it’s correct:

• PNMT is specifically responsible for converting norepinephrine into epinephrine.

• It adds a methyl group to norepinephrine using SAM.

• Its activity is upregulated by cortisol, providing a link between the HPA axis and catecholamine output during stress.

❌ Why the Other Options Are Incorrect:

 Catechol-O-methyltransferase (COMT)

• Not involved in synthesis.

• Function: It degrades catecholamines (epinephrine, norepinephrine, dopamine) by methylation.

 DOPA hydroxylase

• There’s no such enzyme in catecholamine biosynthesis.

• Possibly a confusion with DOPA decarboxylase, which converts DOPA to dopamine — an earlier step than what the question asks.

 Tyrosine hydroxylase

• Converts tyrosine to DOPA.

• It’s the first and rate-limiting step of catecholamine synthesis — but not involved in converting norepinephrine to epinephrine.

 Monoamine oxidase (MAO)

• Also involved in catecholamine breakdown, not synthesis.

• MAO oxidatively deaminates catecholamines, helping terminate their action.

🧬 How Thyroid Hormones Are Made:

Thyroid hormones — T3 (triiodothyronine) and T4 (thyroxine) — are synthesized in the thyroid gland through the iodination of a specific amino acid:

🔹 Tyrosine:

• It is an aromatic amino acid with a hydroxyl group.

• Incorporated into thyroglobulin, a large glycoprotein produced by follicular cells of the thyroid.

• In the presence of iodine, tyrosine residues on thyroglobulin are iodinated to form:

  • Monoiodotyrosine (MIT)

  • Diiodotyrosine (DIT)

These then combine:

• DIT + DIT → T4

• DIT + MIT → T3

So, tyrosine is the direct precursor and essential building block for thyroid hormones.

❌ Why the Other Options Are Incorrect:

• Glycine

  • ❌ Smallest amino acid, involved in collagen and porphyrin synthesis, not thyroid hormones.

• Phenylalanine

  • ❌ Precursor to tyrosine, but not directly used in thyroid hormone synthesis.

  • Needs to be converted to tyrosine first via phenylalanine hydroxylase.

• Tryptophan

  • ❌ Precursor to serotonin, melatonin, and niacin, not thyroid hormones.

• Valine

  • ❌ Branched-chain amino acid involved in muscle metabolism, not hormone synthesis.

Insulin is a peptide hormone essential for glucose metabolism, lipid storage, and protein synthesis. It is produced by β-cells of the pancreatic islets of Langerhans.

🔹 Structure of Insulin:

• Composed of two chains:

  • A-chain (alpha): 21 amino acids

  • B-chain (beta): 30 amino acids

• Held together by disulfide bonds

• Total: 51 amino acids

✅ So the first, second, third, and fifth statements are all correct.

❌ Incorrect Statement:

• “It increases the activity of hormone-sensitive lipase” → This is incorrect.

🔻 Why?

• Hormone-sensitive lipase (HSL) is an enzyme that breaks down stored triglycerides into free fatty acids.

• Insulin inhibits HSL activity, thereby preventing lipolysis.

• Instead, insulin promotes lipid storage by:

  • Stimulating lipoprotein lipase (LPL) (uptake of circulating fats)

  • Promoting fatty acid synthesis

  • Inhibiting HSL, which would otherwise release fatty acids from adipose tissue

Oxytocin is a peptide hormone made up of 9 amino acids, thus classified as a nonapeptide. Its structure includes:

• A short peptide chain with a disulfide bridge between cysteine residues.

• It is synthesized in the hypothalamus (specifically the paraventricular nucleus) and stored/released by the posterior pituitary (neurohypophysis).

• Functions include stimulating uterine contractions during labor and milk ejection during breastfeeding.

❌ Why the Other Options Are Incorrect:

•  It is an eicosanoid: Eicosanoids are lipid-based signaling molecules (e.g., prostaglandins), not peptides.

•  It is a steroid hormone of around 21 carbons: Steroids like cortisol or aldosterone fit this description, not oxytocin.

•  It is a modified amino acid of tyrosine: This applies to thyroid hormones like thyroxine, not oxytocin.

•  It is a protein hormone of 26 amino acids: This matches vasopressin precursors but not oxytocin.

Glucagon is a peptide hormone secreted by the alpha cells of the pancreatic islets (Islets of Langerhans). It plays a crucial role in glucose homeostasis, especially during fasting or hypoglycemia.

🔬 Structure:

• Glucagon consists of 29 amino acids in a single polypeptide chain.

• It is derived from a larger precursor called proglucagon.

• The active 29-amino-acid sequence is located at the N-terminal of the proglucagon molecule.

• Synthesized and secreted in response to low blood glucose, its main actions are:

  • Stimulating gluconeogenesis

  • Stimulating glycogenolysis

  • Increasing lipolysis

❌ Why the Other Options Are Incorrect:

• 30
  → Slightly more than actual count; glucagon is exactly 29 amino acids long.

• 21
  → This is the length of insulin’s A-chain, not glucagon.

• 40
  → Too long; some regulatory peptides have ~40 aa, but not glucagon.

• 51
  → This is the total number of amino acids in insulin (A-chain = 21, B-chain = 30).

Steroidogenesis refers to the biosynthesis of steroid hormones from cholesterol in endocrine tissues such as the adrenal cortex, gonads, and placenta.

The rate-limiting step — i.e., the slowest and most tightly regulated step in this pathway — is:

Conversion of cholesterol to pregnenolone

This reaction is catalyzed by the enzyme cholesterol side-chain cleavage enzyme, also known as P450scc or desmolase.

🧪 Key Points about Desmolase (P450scc):

• Located in the inner mitochondrial membrane

• Requires NADPH, oxygen, and cytochrome P450

• Regulated primarily by ACTH in the adrenal cortex

• Once pregnenolone is produced, it can be shunted into:

  • Glucocorticoid pathway (cortisol)

  • Mineralocorticoid pathway (aldosterone)

  • Sex steroid pathway (androgens/estrogens)

❌ Why the Other Options Are Incorrect:

• 11β-Hydroxylase
  → Converts 11-deoxycortisol → cortisol; not rate-limiting.
  ✅ Important but comes late in the pathway.

• 3β-Hydroxysteroid dehydrogenase
  → Converts pregnenolone → progesterone; also key, but after pregnenolone is made.

• 17α-Hydroxylase
  → Important for sex steroid and cortisol production, but not rate-limiting.

• 21-Hydroxylase
  → Converts progesterone → deoxycorticosterone; again, important, but downstream.

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders characterized by enzyme defects in the cortisol biosynthetic pathway of the adrenal cortex. These defects lead to low cortisol, compensatory ACTH elevation, and adrenal hyperplasia.

🧪 21-Hydroxylase Deficiency:

• Most common cause of CAH — accounts for about 90–95% of cases.

• The 21-hydroxylase enzyme is responsible for:

  • Converting progesterone → 11-deoxycorticosterone (mineralocorticoid pathway)

  • Converting 17-hydroxyprogesterone → 11-deoxycortisol (glucocorticoid pathway)

🔄 Result of deficiency:

• ↓ Cortisol → Loss of negative feedback → ↑ ACTH → adrenal hyperplasia

• ↓ Aldosterone (in severe forms) → salt-wasting crisis

• ↑ Androgens (diverted precursors) → virilization, precocious puberty, ambiguous genitalia in females

❌ Why the Other Options Are Incorrect:

• 18-Hydroxylase
  → Involved in aldosterone synthesis, not commonly defective in CAH.

• 17,20-lyase
  → Involved in sex steroid production; rare deficiency, causes ambiguous genitalia and sexual development delays.

• 11β-Hydroxylase
  → Second most common CAH cause (~5%); causes hypertension due to buildup of 11-deoxycorticosterone (a mineralocorticoid).

• 17α-Hydroxylase
  → Rare; leads to hypertension, hypogonadism, and absent secondary sexual characteristics.

Insulin is a peptide hormone — not a steroid — and is made up of two polypeptide chains:

• An A chain (21 amino acids)

• A B chain (30 amino acids)

These two chains are linked by two disulfide bonds, and a third disulfide bond is present within the A chain.

This arrangement makes insulin a heterodimer, meaning it is composed of two non-identical subunits.

🧬 Key Structural Points:

• Synthesized initially as preproinsulin, which is cleaved to proinsulin, and then to active insulin + C-peptide

• Stored in secretory granules in beta cells of the pancreas

• Released in response to elevated blood glucose levels

❌ Why the Other Options Are Incorrect:

• It is a steroid hormone
  → ❌ Incorrect. Steroid hormones are lipid-derived, and insulin is a protein hormone.

• It is a glycolipid
  → ❌ Incorrect. Glycolipids are lipids with a carbohydrate attached. Insulin is purely a peptide.

• It is an amino acid
  → ❌ Incorrect. Insulin is composed of multiple amino acids (51 in total), not a single one.

• It is a homodimeric protein
  → ❌ Incorrect. A homodimer consists of two identical subunits, but insulin has two different chains (A and B) — making it a heterodimer.

All steroid hormones are derived from a common precursor molecule: cholesterol. This process occurs primarily in the mitochondria and smooth endoplasmic reticulum of steroidogenic tissues, like the adrenal cortex, gonads, and placenta.

🔬 The Pathway:

1. Cholesterol → transported into mitochondria

2. In mitochondria, cholesterol is converted into pregnenolone by the enzyme desmolase (cholesterol side-chain cleavage enzyme).

3. Pregnenolone is the first intermediate, but not the ultimate precursor — it’s a derivative of cholesterol.

4. From pregnenolone, the pathway diverges into:

   • Glucocorticoids (e.g., cortisol)

   • Mineralocorticoids (e.g., aldosterone)

   • Sex steroids (e.g., testosterone, estrogen, progesterone)

❌ Why the Other Options Are Incorrect:

• Pregnenolone
  → Important intermediate, but it is made from cholesterol.
  ❌ Not the original precursor.

• Pregnanediol
  → A metabolite of progesterone, found in urine.
  ❌ Not a precursor — it’s a breakdown product.

• Estrogen
  → A final hormone, synthesized downstream in the steroid pathway.
  ❌ Not a precursor.

• Valine
  → An essential amino acid, unrelated to steroidogenesis.
  ❌ Has no role in steroid hormone synthesis.

The brain primarily relies on glucose as its main energy source under normal physiological conditions because:

• Glucose can readily cross the blood-brain barrier via specific glucose transporters (GLUT1 and GLUT3).

• It is efficiently metabolized by neurons and glial cells to generate ATP, essential for maintaining ion gradients, neurotransmission, and other cellular functions.

• Although the brain can adapt to use ketone bodies during prolonged fasting or starvation, glucose remains the primary and preferred fuel.

❌ Why the Other Options Are Incorrect:

•  Fatty acids: Do not cross the blood-brain barrier efficiently and are not used as a primary energy source by the brain.

•  Glutamine: Amino acid involved in neurotransmission and nitrogen transport, but not a primary energy substrate.

•  Creatine: Involved in short-term energy storage in muscles and brain but not a main energy substrate.

• Alanine: Amino acid; can serve as a substrate for gluconeogenesis but not a primary energy source for the brain.

Somatostatin is a peptide hormone with two biologically active forms:

• Somatostatin-14 (14 amino acids)

• Somatostatin-28 (28 amino acids)

In the pancreas, somatostatin is secreted by delta (δ) cells in the islets of Langerhans in the form of somatostatin-14.

🧬 Key Roles of Somatostatin:

• Inhibits the secretion of:

  • Insulin

  • Glucagon

  • Pancreatic polypeptide

  • Growth hormone (in the anterior pituitary)

  • Gastrointestinal hormones like gastrin and secretin

It acts as a paracrine inhibitor to help regulate neighboring islet cell activity and digestive processes.

❌ Why the Other Options Are Incorrect:

• Glucagon
  → A 29-amino-acid peptide secreted by alpha cells in the pancreas.
  ❌ Not 14 amino acids.

• Cortisol
  → Not a peptide at all. It’s a steroid hormone made in the adrenal cortex.
  ❌ Wrong type of molecule.

• Pancreatic polypeptide
  → Secreted by PP (F) cells in the pancreas; made up of 36 amino acids.
  ❌ Not 14 amino acids.

• Insulin
  → Composed of 51 amino acids (A-chain and B-chain linked by disulfide bonds).
  ❌ Not 14 amino acids.

Glucocorticoids (primarily cortisol) have complex metabolic effects that help the body respond to stress and maintain energy homeostasis. Their effects can be summarized as:

🔹 Anti-Insulin Effects (Peripheral):

• Decreased glucose uptake in peripheral tissues (muscle, adipose), leading to insulin resistance

• Increased protein catabolism in muscles

• Increased lipolysis in adipose tissue
  → These contribute to hyperglycemia, muscle wasting, and fat redistribution.

🔹 Anabolic Effects (Liver):

• Stimulate gluconeogenesis and glycogen synthesis
  → Promotes increased glucose output

Thus, glucocorticoids are catabolic in peripheral tissues and anabolic in the liver—helping to increase blood glucose levels, especially during fasting or stress.

❌ Why the Other Options Are Incorrect:

•  Enhances energy provision: Partially true, but too vague and nonspecific.

•  Causes the synthesis of significant proteins: Actually, they cause protein breakdown, especially in muscles.

•  Insulin function enhancement: Glucocorticoids oppose insulin action.

•  Excessive catabolism of proteins, fats, and carbohydrates: Glucocorticoids are catabolic in protein and fat metabolism, but not carbohydrates directly—they promote gluconeogenesis and glucose sparing, not breakdown of carbs.

Thyroid hormones (T₃ and T₄) are synthesized in the thyroid gland and are derived from the amino acid tyrosine.

• Tyrosine residues on thyroglobulin undergo iodination to form monoiodotyrosine (MIT) and diiodotyrosine (DIT).

• Coupling of these iodinated tyrosines forms:

  • T₃ (triiodothyronine) = MIT + DIT

  • T₄ (thyroxine) = DIT + DIT

Thus, thyroid hormones are iodinated derivatives of tyrosine, making tyrosine their biochemical precursor.

❌ Why the Other Options Are Incorrect:

• . Testosterone,  Estrogen,  Progesterone: These are steroid hormones, derived from cholesterol, not amino acids.

• Growth hormone (GH): A protein hormone composed of amino acid chains, but not derived from tyrosine—it is synthesized as a gene product by the anterior pituitary.

The smooth endoplasmic reticulum (SER) is the primary site for the synthesis of steroid hormones in cells.

This is because:

• Steroid hormones are lipid-soluble molecules derived from cholesterol.

• The SER is rich in enzymes required for:

  • Cholesterol uptake and storage

  • Hydroxylation

  • Conversion into steroid intermediates like progesterone, cortisol, aldosterone, estrogen, and testosterone.

🔬 Organs with Abundant SER (Steroid-Producing Cells):

• Adrenal cortex (cortisol, aldosterone)

• Ovaries (estrogen, progesterone)

• Testes (testosterone)

❌ Why the Other Options Are Incorrect:

All catecholamines — including dopamine, norepinephrine, and epinephrine — are synthesized from the amino acid tyrosine. This pathway is crucial in both the central nervous system and the adrenal medulla.

🧬 Catecholamine Synthesis Pathway:

1. Tyrosine
   ⬇️ (via tyrosine hydroxylase)

2. L-DOPA
   ⬇️ (via DOPA decarboxylase)

3. Dopamine
   ⬇️ (via dopamine β-hydroxylase)

4. Norepinephrine
   ⬇️ (via phenylethanolamine-N-methyltransferase — PNMT)

5. Epinephrine

• Tyrosine is often obtained from the diet or synthesized from phenylalanine.

❌ Why the Other Options Are Incorrect:

🧠 Memory Tip:

Tyrosine → “T” for Trigger of the catecholamine cascade!

🔹 Glucocorticoids (e.g., cortisol):

These are steroid hormones secreted by the zona fasciculata of the adrenal cortex. They play a major role in metabolism, immune modulation, and stress response.

🔹 Effect on Lipid Metabolism:

One of the key effects of glucocorticoids is to mobilize energy stores, especially under stress (e.g., fasting, infection). This includes:

• Promoting lipolysis — the breakdown of triglycerides (TAGs) in adipose tissue into glycerol and free fatty acids (FFAs).

• The FFAs are then released into plasma to be used by tissues for energy production (especially in muscle and liver).

🔹 How does this happen?

Glucocorticoids upregulate the expression and activity of:

👉 Hormone-sensitive lipase (HSL), which catalyzes:

• TAG → DAG → MAG → glycerol + FFAs

This enzyme is normally stimulated by catecholamines, but glucocorticoids enhance its sensitivity and expression, amplifying its effect.

✅ Hence, increased lipolysis via HSL activation leads to increased plasma FFAs.

❌ Why the Other Options Are Incorrect:

📌 Summary:

🔬 Adrenal Medulla and Its Hormones:

The adrenal medulla is the inner part of the adrenal gland, composed of chromaffin cells. These cells produce catecholamines, primarily:

• Epinephrine (adrenaline)

• Norepinephrine (noradrenaline)

• Dopamine (to a lesser extent)

🧬 Biosynthetic Pathway:

All these catecholamines are synthesized from the amino acid tyrosine, following this sequence:

1. Tyrosine → (via tyrosine hydroxylase) → L-DOPA

2. L-DOPA → (via DOPA decarboxylase) → Dopamine

3. Dopamine → (via dopamine β-hydroxylase) → Norepinephrine

4. Norepinephrine → (via phenylethanolamine-N-methyltransferase) → Epinephrine

So, tyrosine is the direct precursor of all adrenal medullary hormones.

❌ Why the Other Options Are Incorrect:

Phenylalanine – ❌

While phenylalanine is a precursor to tyrosine (via phenylalanine hydroxylase), the actual substrate used by adrenal medulla cells to make catecholamines is tyrosine, not phenylalanine directly.

Valine – ❌

Valine is a branched-chain amino acid, involved in energy metabolism and muscle function, not catecholamine synthesis.

Tryptophan – ❌

Tryptophan is the precursor of serotonin and melatonin, not catecholamines.

Arginine – ❌

Arginine is involved in nitric oxide synthesis, urea cycle, and creatine synthesis—not catecholamines.

Role of Insulin in Muscle Carbohydrate Metabolism:

• Primary action: Insulin facilitates the uptake of glucose into muscle cells.

• Mechanism: Insulin triggers the translocation of GLUT4 (Glucose Transporter type 4) from intracellular vesicles to the muscle cell membrane.

• This increases glucose transport from the bloodstream into muscle cells.

• Once inside, glucose can be used for glycolysis or stored as glycogen.