Renal – Biochem

All the listed conditions — urine retention, chronic cystitis, anemia, obstructing gastric ulcers, and alkaline therapy — contribute to a rise in systemic or urinary pH, leading to a state of alkalosis (excess alkalinity).

Mechanisms:

• Urine retention & chronic cystitis: allow bacterial decomposition of urea → ammonia formation, which makes the urine alkaline.

• Obstructing gastric ulcers: cause loss of gastric acid (HCl) through vomiting → increased blood bicarbonate → metabolic alkalosis.

• Alkaline therapy: direct intake of bicarbonate or antacids → increases systemic alkalinity.

• Anemia may occur secondarily (e.g., from chronic gastric loss) but isn’t the direct cause — it’s part of the overall systemic disturbance.

Hence, collectively these conditions point toward excess alkalinity (alkalosis).

❌ Why the Other Options Are Wrong

• Excess acidity: opposite effect — would occur in metabolic acidosis.

• Retention of acid metabolites: linked to renal failure or poor perfusion, not to these conditions.

• Raised pCO₂: seen in respiratory acidosis, not relevant here.

• Raised specific gravity: depends on dehydration, not acid–base status.

Folate (in its active form, tetrahydrofolate — THF) donates one-carbon units during the synthesis of purine rings.

• Specifically, N¹⁰-formyl-THF contributes carbon atoms at positions C₂ and C₈ of the purine structure.

• Without folate, purine synthesis — and thus DNA and RNA production — slows dramatically, leading to megaloblastic anemia due to impaired cell division.

❌ Why the Other Options Are Wrong:

Thiamine (Vitamin B₁):

• Functions as thiamine pyrophosphate (TPP) in carbohydrate metabolism (e.g., pyruvate dehydrogenase, α-ketoglutarate dehydrogenase).

• Plays no role in purine synthesis.

Biotin:

• Acts as a CO₂ carrier in carboxylation reactions (e.g., acetyl-CoA carboxylase, pyruvate carboxylase).

• Not involved in transferring one-carbon units for purines.

Flavin (Vitamin B₂):

• Component of FAD/FMN, coenzymes for oxidation-reduction reactions.

• Does not donate carbon groups for nucleotide synthesis.

Caltrate:

• A calcium supplement, unrelated to metabolic cofactors or nucleotide biosynthesis.

The patient’s description — sudden, intensely painful swelling of the big toe (podagra) with needle-shaped urate crystals in the synovial fluid — is classic for gout.
Although most gout is acquired (due to excess uric acid production or decreased excretion), an enzyme deficiency in purine metabolism can predispose to hyperuricemia.

The key enzyme here is HGPRT (Hypoxanthine-Guanine Phosphoribosyltransferase), part of the purine salvage pathway, which normally salvages hypoxanthine and guanine back to IMP and GMP using PRPP.

When HGPRT is deficient or partially defective, the salvage pathway fails → PRPP accumulates → de novo purine synthesis increases → excess uric acid production → gout.

Partial deficiency = Kelley–Seegmiller syndrome (adult gout).
Complete deficiency = Lesch–Nyhan syndrome (neurobehavioral issues + self-mutilation).

❌ Why the Other Options Are Wrong

• Alkaline phosphatase, PRPP:
  Alkaline phosphatase isn’t involved in purine metabolism; PRPP is a substrate, not an enzyme.

• Adenosine deaminase + HGPRT:
  ADA deficiency → SCID, not gout.

• HGPRT + PRPP:
  PRPP (phosphoribosyl pyrophosphate) isn’t an enzyme, so this combination is invalid.

• Phosphoribosyl pyrophosphate:
  It’s a substrate synthesized by PRPP synthetase — overactivity of PRPP synthetase may cause gout, but deficiency does not.

This presentation describes orotic aciduria, a rare autosomal recessive disorder caused by a deficiency of uridine monophosphate (UMP) synthase — an enzyme complex that catalyzes the final two steps of de novo pyrimidine synthesis:

1️⃣ Orotate phosphoribosyltransferase (OPRTase) converts orotic acid → orotidine monophosphate (OMP).
2️⃣ OMP decarboxylase then converts OMP → uridine monophosphate (UMP).

When this enzyme is deficient, orotic acid accumulates in the urine, and pyrimidine nucleotides (especially UMP) are deficient. This leads to megaloblastic anemia and growth retardation, because DNA synthesis is impaired.

Treatment: Administration of uridine bypasses the enzyme block — it gets converted to UMP, replenishing pyrimidine pools, correcting the anemia, and alleviating symptoms.

❌ Why the Other Options Are Wrong

• Adenine & Guanine:
  Purine bases — supplementing them won’t fix a pyrimidine synthesis defect.

• Hypoxanthine:
  Also a purine precursor; relevant to Lesch–Nyhan syndrome, not orotic aciduria.

• Thymidine:
  A pyrimidine nucleoside but downstream of UMP — it cannot substitute for the missing UMP synthase function.

Tissues that lack de novo purine synthesis (like the brain and erythrocytes) maintain their adenine nucleotide pool through the salvage pathway. The key enzyme here is adenine phosphoribosyltransferase (A-PRT), which converts adenine + PRPP → AMP + PPᵢ — efficiently recycling adenine into usable nucleotides.

Why others are wrong:
❌ Adenylate kinase — interconverts AMP, ADP, and ATP, but doesn’t form new adenine nucleotides.
❌ ATP uptake from blood — ATP cannot cross cell membranes; cells must synthesize or salvage it internally.
❌ Nucleoside phosphorylase — involved in nucleotide breakdown, not salvage.
❌ HGPRT (hypoxanthine-guanine phosphoribosyltransferase) — salvages hypoxanthine and guanine, not adenine.

Frothy urine and periorbital edema (morning swelling around the eyes) are classic signs of proteinuria, often due to glomerular damage (as seen in nephrotic syndrome). The loss of plasma proteins like albumin lowers plasma oncotic pressure, leading to fluid retention and edema.

Why others are wrong:
❌ Fats — may appear in nephrotic syndrome as fatty casts, but protein is the primary abnormality.
❌ Glucose — found in diabetes mellitus when blood glucose exceeds the renal threshold, but not the main cause of frothy urine.
❌ Ketone bodies — appear in uncontrolled diabetes or starvation, not in edema-related conditions.
❌ Uric acid — elevated in gout or tumor lysis, not responsible for frothy urine.

Creatinine clearance is a clinical marker used to estimate the glomerular filtration rate (GFR) — a measure of glomerular function. Creatinine is freely filtered by the glomeruli and only slightly secreted by the tubules, so its clearance closely reflects GFR under normal conditions.

Why others are wrong:
❌ Bladder function — evaluated by post-void residual or urodynamic studies, not creatinine clearance.
❌ Measurement of skeletal muscle mass — creatinine production relates to muscle mass, but clearance reflects kidney filtration, not muscle size.
❌ Tubular function — assessed using tests like PAH clearance or concentration–dilution tests.
❌ Urolithiasis — refers to stone formation, unrelated to clearance values.

IMP is the common precursor for both AMP (adenosine monophosphate) and GMP (guanosine monophosphate) in purine nucleotide synthesis.
From IMP:

• AMP is formed via adenylosuccinate synthase (using GTP).

• GMP is formed via IMP dehydrogenase and GMP synthase (using ATP).

Why others are wrong:
❌ Xanthine monophosphate (XMP) — an intermediate only in GMP synthesis, not for AMP.
❌ Cytidine monophosphate (CMP) — part of pyrimidine pathway.
❌ Hypoxanthine monophosphate (HMP) — not a standard intermediate; IMP already contains hypoxanthine.
❌ Thymidine monophosphate (TMP) — a pyrimidine nucleotide used in DNA synthesis, unrelated to purines.

CTP synthase catalyzes the amination of UTP to form CTP, using glutamine as the amino group donor and ATP as an energy source. This is a key regulatory step in pyrimidine nucleotide biosynthesis.

Why others are wrong:
❌ CTP kinase — would phosphorylate, not aminate.
❌ CTP synthetase — incorrect name; the correct enzyme is CTP synthase.
❌ Ribonucleotide reductase — converts ribonucleotides to deoxyribonucleotides, not UTP to CTP.
❌ UTP transferase — no such enzyme in this pathway.

In the GLDH kinetic method, urea is first converted to ammonia, which then participates in a reaction catalyzed by glutamate dehydrogenase (GLDH).
This reaction involves the oxidation of NADH to NAD⁺, and since NADH absorbs light at 340 nm (while NAD⁺ does not), the decrease in absorbance is directly proportional to the urea concentration.

❌ Why Others Are Wrong:

• To measure NAD⁺:
  NAD⁺ does not absorb light at 340 nm, so it’s not measured.

• To monitor urea directly:
  Urea itself is colorless and doesn’t absorb at this wavelength.

• To calculate 2-oxoglutarate conversion:
  2-oxoglutarate does not form a colored complex measurable at 340 nm.

• To measure increase in urea:
  The assay measures NADH oxidation, not urea directly.

Lesch-Nyhan syndrome arises from a defect in the purine salvage pathway, causing excessive uric acid accumulation.
This leads to neurological dysfunction, self-injurious behavior, and motor abnormalities due to the toxic effects of excess metabolites on the brain.

❌ Why Others Are Wrong:

• ALP: Indicates bone or liver activity — unrelated to this inherited metabolic defect.

• AST: Liver enzyme — no link with purine metabolism or neurological symptoms.

• LDH: Nonspecific enzyme — elevated in many tissue injuries, not diagnostic here.

• SGPT: Reflects liver damage, not neurological or metabolic disorders.

The described case is classic for Lesch-Nyhan syndrome, a genetic deficiency of HGPRT (hypoxanthine-guanine phosphoribosyltransferase).
This defect leads to accumulation of uric acid, causing neurological abnormalities, self-mutilation, and urinary stones due to uric acid crystallization.
Hence, serum uric acid is the most valuable diagnostic test.

❌ Why Others Are Wrong:

• ALP (Alkaline phosphatase):
  Related to bone or liver disorders, not purine metabolism.

• LDH (Lactate dehydrogenase):
  Non-specific; elevated in tissue damage but not diagnostic here.

• LEAD:
  Lead levels detect lead poisoning, which can cause neurological signs but not self-mutilation or uric acid stones.

• SGPT (ALT):
  Reflects liver function, not relevant to this inherited enzyme deficiency.

In respiratory alkalosis, carbon dioxide (CO₂) levels drop due to hyperventilation, leading to a rise in blood pH (more basic).
To compensate, the kidneys excrete more bicarbonate (HCO₃⁻) to lower the pH back toward normal.

❌ Why Others Are Wrong:

• Decreased excretion of bicarbonate:
  Would retain HCO₃⁻ and worsen alkalosis, not fix it.

• Decreased hydrogen ion excretion:
  Happens slightly, but it’s not the main renal mechanism — the key adjustment is bicarbonate loss.

• Increased reabsorption of hydrogen ions:
  Hydrogen ions are not “reabsorbed” — they’re secreted into urine. So this option doesn’t physiologically make sense.

• Increased synthesis of bicarbonate:
  Would add more base to blood, worsening alkalosis, opposite of what’s needed.

Phosphoribosyl pyrophosphate (PRPP) is formed when ribose-5-phosphate (from the hexose monophosphate shunt) reacts with ATP, transferring two phosphate groups to generate PRPP. This reaction is catalyzed by PRPP synthetase (also called ribose-phosphate diphosphokinase). PRPP is the key activated sugar donor in purine and pyrimidine nucleotide synthesis.

Why the others are wrong:

• ❌ Adenylosuccinate lyase – Involved in converting adenylosuccinate to AMP in the later steps of purine synthesis.

• ❌ Adenylosuccinate synthase – Catalyzes formation of adenylosuccinate from IMP, not PRPP.

• ❌ Cyclohydrolase – Acts later in the purine ring formation process (e.g., in formylation steps).

• ❌ PRPP glutamyl amidotransferase – Uses PRPP as a substrate in the first committed step of purine synthesis, but does not form PRPP.

In metabolic acidosis without respiratory compensation, the primary disturbance is a decrease in bicarbonate (HCO₃⁻), which lowers blood pH (acidemia). Since respiratory compensation hasn’t occurred yet, pCO₂ remains unchanged initially — it only falls later when hyperventilation begins.

Why the others are wrong:

• ❌ Bicarbonate ion – Decreases (it’s the primary abnormality).

• ❌ Hydrogen ion – Increases, causing acidosis.

• ❌ Anion gap – Often increases (in high anion gap acidosis).

• ❌ pH – Decreases because of the fall in bicarbonate.

✅ Acidosis
Renal glutaminase activity increases in metabolic acidosis to generate ammonia for H⁺ excretion.

Explanation:

• Glutaminase in the proximal tubular cells converts glutamine → glutamate + NH₃ (ammonia).

• Ammonia binds to H⁺ in the tubular fluid → NH₄⁺ (ammonium), which is excreted in urine.

• This process allows the kidney to excrete excess acid while regenerating bicarbonate (HCO₃⁻) for the blood.

• Therefore, renal glutaminase activity rises significantly during acidosis, not in alkalosis or shock.

Explanation of the Incorrect Options

❌ Hemorrhage
Leads to RAAS activation and sodium/water retention, not increased glutaminase activity.

❌ Alkalosis
Glutaminase activity decreases in alkalosis because less H⁺ needs to be excreted.

❌ Shock
Involves hypoperfusion and lactic acidosis, but the direct renal enzyme response is tied specifically to acidosis, not shock itself.

❌ All of these
Incorrect, because glutaminase specifically increases in acidosis only.

✅ Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) enzyme
Lesch-Nyhan syndrome is caused by a deficiency of HGPRT, leading to impaired purine salvage.

Explanation:

• HGPRT normally salvages hypoxanthine and guanine by converting them back into IMP and GMP using PRPP.

• In Lesch-Nyhan syndrome, absence of HGPRT → purine salvage is defective → excess PRPP and de novo purine synthesis.

• This leads to hyperuricemia, gout, kidney stones, and neurological/behavioral symptoms (self-mutilation, choreoathetosis).

Explanation of the Incorrect Options

❌ Inosine monophosphate dehydrogenase
Catalyzes IMP → XMP in purine synthesis; not defective in Lesch-Nyhan.

❌ Guanine monophosphate synthase
Converts XMP → GMP; not affected in this disease.

❌ Xanthine oxidase
Converts hypoxanthine → xanthine → uric acid; inhibited by allopurinol, but deficiency is not linked to Lesch-Nyhan.

❌ None of these
Incorrect, because HGPRT is the enzyme involved.

✅ Aspartate
Aspartate donates an amino group in the reaction converting IMP to AMP.

Explanation:

• In purine nucleotide biosynthesis, IMP (inosine monophosphate) is the branch point for AMP and GMP synthesis.

• To form AMP, IMP is first converted to adenylosuccinate by adenylosuccinate synthetase, using aspartate as the nitrogen donor.

• Adenylosuccinate is then cleaved by adenylosuccinate lyase to yield AMP and fumarate.

This step ensures that AMP synthesis requires GTP as an energy source and aspartate as the amino group donor.

Explanation of the Incorrect Options

❌ Carbon dioxide
Used earlier in purine synthesis (e.g., in carboxylation steps), not in the conversion of IMP to AMP.

❌ Glutamate
Glutamine (not glutamate) donates nitrogen at other steps, but not here.

❌ Glycine
Incorporated into the purine ring during the early steps of de novo synthesis, not at the IMP → AMP branch.

❌ Water
Not a nitrogen donor in this reaction.

✅ Xanthine oxidase
Xanthine oxidase catalyzes the oxidation of hypoxanthine to xanthine, and further to uric acid.

Explanation:
In purine catabolism, hypoxanthine is first oxidized to xanthine, and then xanthine is oxidized to uric acid.

• Both steps are catalyzed by xanthine oxidase, a molybdenum-containing enzyme.

• This pathway is clinically relevant because excess uric acid leads to gout.

• Drugs like allopurinol inhibit xanthine oxidase, reducing uric acid formation.

Explanation of the Incorrect Options

❌ Xanthine dehydrogenase
A related enzyme form, but in humans, the main conversion is through xanthine oxidase.

❌ Xanthine hydrogenase
Not an enzyme recognized in purine metabolism.

❌ Xanthine synthase
Not involved in this pathway; no such enzyme in standard purine degradation.

❌ None of these
Incorrect, because xanthine oxidase is the correct answer.

✅ Bicarbonate buffer
The bicarbonate–carbonic acid buffer system is the most important extracellular buffer that maintains blood pH around 7.4.

Explanation:
The bicarbonate buffer system (H₂CO₃ / HCO₃⁻) is the primary regulator of blood pH because:

• Its pKa (6.1) is close enough to physiological pH (7.4) to be effective.

• It is an open system: CO₂ (acid component) can be exhaled by the lungs and bicarbonate (base component) can be regulated by the kidneys.

• This dual regulation makes it highly adaptable to maintain homeostasis.

Explanation of the Incorrect Options

❌ Phosphate buffer
Important in the intracellular fluid and renal tubules, but not the main buffer in plasma.

❌ Chloride buffer
Chloride shift (Hamburger phenomenon) helps in RBCs, but it is not the dominant systemic buffer.

❌ Hydrogen buffer
Not a recognized physiological buffer system.

❌ Protein buffer
Proteins (especially hemoglobin) play an important role inside RBCs, but systemically, bicarbonate is the strongest.

Nucleic acid digestion (DNA and RNA) occurs primarily in the small intestine, especially the duodenum.

• Pancreatic nucleases (DNAse and RNAse) break down nucleic acids into smaller nucleotides.

• These nucleotides are further digested by brush-border enzymes (nucleotidases, nucleosidases) into nitrogenous bases, sugars, and phosphate, which can then be absorbed.

• Minimal digestion occurs in the mouth or stomach; the small intestine is the major site.

❌ Incorrect Answer Breakdown:

• Esophagus: Functions only as a passage for food; no enzymatic digestion occurs here.

• Appendix: A lymphoid organ with immune functions; not involved in digestion.

• Rectum: Stores feces before defecation; no role in digestion.

• Mouth: Only mechanical digestion and some carbohydrate breakdown (salivary amylase). No nucleic acid digestion occurs here.

Step-by-Step Reasoning

1. Adenine phosphoribosyltransferase (APRT) reaction

• APRT is part of the purine salvage pathway.

• It catalyzes:

Adenine+PRPP⟶AMP+PPiAdenine+PRPP⟶AMP+PPi

• Here, PRPP (phosphoribosyl pyrophosphate) donates the ribose-5-phosphate to adenine to form AMP.

2. Check other options

• Hexose monophosphate shunt → produces NADPH and ribose-5-phosphate but is not directly the donor in this reaction. ❌

• Carbon dioxide → unrelated. ❌

• Dihydrofolate → cofactor in thymidylate synthesis, not APRT reaction. ❌

• Adenosine → substrate/product? Adenine is the substrate; adenosine is not a donor. ❌

Correct Answer: Phosphoribosyl diphosphate (PRPP) ✅

Step-by-Step Reasoning

1. Salvage pathway overview

• The salvage pathway is a metabolic route in which free bases (purines and pyrimidines) are recycled to form nucleotides, instead of being synthesized de novo.

• This pathway is energy-efficient compared to de novo synthesis.

2. Function and benefit

• Ensures a continuous supply of nucleotides for DNA/RNA synthesis even when de novo synthesis is slow or energy-limited.

• Helps conserve energy and resources in the cell.

3. Check each option

• Provides continuous supply of nucleotides → ✅ correct, matches main purpose.

• Provides continuous supply of nucleic acid → incorrect; nucleic acids are polymers, salvage pathway supplies monomeric nucleotides, not polymeric nucleic acids. ❌

• Increases production of nucleic acid → indirect effect; not primary benefit. ❌

• Increases degradation of nucleotides → opposite function. ❌

• Increases synthesis of nucleotides → partially correct but de novo synthesis is separate; salvage recycles existing bases. ❌

Correct Answer: Provides continuous supply of nucleotides ✅

✅ Ability to dissolve many solutes
Water is called a universal solvent because its polarity allows it to dissolve a wide range of solutes.

Water molecules are polar, with partial positive charges on the hydrogen atoms and a partial negative charge on the oxygen atom. This polarity enables water to interact with and stabilize ions and polar molecules, effectively breaking ionic bonds and surrounding solutes in a hydration shell. This property explains why water dissolves salts, sugars, amino acids, and many other compounds, earning it the title of “universal solvent.”

Explanation of the Incorrect Options

❌ Having strong hydrogen bonds
Hydrogen bonds make water cohesive and give it high boiling and melting points, but they are not the main reason it dissolves solutes.

❌ Ability to split into ions
Water can ionize into H⁺ and OH⁻, but this is not why it is a universal solvent.

❌ Taking any shape
This is a property of liquids in general, not specifically related to solvent capability.

❌ None of these
Incorrect, because water does dissolve many solutes.

✅ Uracil
Deamination of cytosine converts it into uracil.

Cytosine can undergo spontaneous deamination, where the amino group (–NH₂) is replaced by a keto group (=O). This converts cytosine into uracil, a base normally found in RNA but abnormal in DNA. If unrepaired, this mutation leads to a G≡C → A=U (or T) transition, which is a common mutational event in DNA.

Explanation of the Incorrect Options

❌ Methyl cytosine
This is a product of DNA methylation, not deamination.

❌ Cytidylic acid
This is a nucleotide (cytidine monophosphate, CMP), not a deamination product.

❌ Tyrosine
An amino acid, unrelated to nucleic acid base deamination.

❌ Adenine
A purine base; cytosine deamination does not yield adenine.

✅ Glutamine
Glutamine donates nitrogen atoms in both purine and pyrimidine nucleotide synthesis.

Glutamine acts as a nitrogen donor in multiple enzymatic reactions.

• In purine synthesis, glutamine donates nitrogen at the N3 and N9 positions.

• In pyrimidine synthesis, glutamine donates nitrogen for the carbamoyl phosphate (via carbamoyl phosphate synthetase II).

This dual role makes glutamine unique compared to other amino acids in nucleotide biosynthesis.

Explanation of the Incorrect Options

❌ None of these
Incorrect, because glutamine indeed contributes nitrogen in both pathways.

❌ Aspartate
Aspartate contributes nitrogen, but only to a limited extent: it provides N1 in purine rings and contributes to pyrimidine rings. However, it is not involved in both pathways as extensively as glutamine.

❌ Glycine
Important for purine synthesis (provides C4, C5, N7) but not for pyrimidine synthesis.

❌ Valine
Not involved in nucleotide base synthesis. It plays a role in protein synthesis and metabolism, not nitrogen donation here.

✅ Guanine monophosphate and adenine monophosphate
IMP is the common precursor for both AMP and GMP in the purine nucleotide biosynthesis pathway.

Inosine monophosphate (IMP):

• IMP is formed during de novo purine synthesis.

• It acts as the branch point precursor for:

  • Adenosine monophosphate (AMP) via conversion through adenylosuccinate.

  • Guanosine monophosphate (GMP) via conversion through xanthosine monophosphate (XMP).

Thus, IMP → AMP + GMP are the two end products.

Note: Cytosine, thymine, and uracil nucleotides belong to the pyrimidine pathway, not derived from IMP.

Explanation of the Incorrect Options

❌ Adenine monophosphate and cytosine monophosphate
Cytosine monophosphate (CMP) is a pyrimidine, not derived from IMP.

❌ Cytosine monophosphate and thymine monophosphate
Both pyrimidines — not linked to IMP.

❌ Cytosine monophosphate and guanine monophosphate
CMP (pyrimidine) is not derived from IMP; GMP is correct, but the pair is wrong.

❌ Thymine monophosphate and adenine monophosphate
Thymine monophosphate (TMP) is also a pyrimidine product (from dUMP), not from IMP.

❌ Guanine monophosphate and adenine monophosphate
This is correct — both are purine nucleotides derived from IMP.

✅ Dihydropteroate synthase
Sulfonamides are structural analogs of para-aminobenzoic acid (PABA) and competitively inhibit dihydropteroate synthase, blocking folate synthesis in bacteria.

Mechanism:

• Bacteria must synthesize their own folic acid de novo, unlike humans who obtain it from diet.

• Sulfonamides mimic PABA, a substrate for dihydropteroate synthase.

• By competitively inhibiting this enzyme, sulfonamides prevent formation of dihydropteroic acid, an essential precursor of folic acid.

• This blocks production of tetrahydrofolate (THF), required for nucleotide synthesis, thereby inhibiting bacterial growth (bacteriostatic effect).

Explanation of the Incorrect Options

❌ Dihydrofolate reductase
Inhibited by trimethoprim (prokaryotes) and methotrexate (eukaryotes), not by sulfonamides.

❌ Peptidyl transferase
Inhibited by chloramphenicol, which blocks peptide bond formation at the 50S ribosome.

❌ Amidotransferase
Important in purine synthesis but not the target of sulfonamides.

❌ Topoisomerase
Inhibited by fluoroquinolones (e.g., ciprofloxacin), not sulfonamides.

Pure water (distilled water):

1. Solvent properties:

   • Water is known as the “universal solvent” because it can dissolve many ionic and polar substances.

2. Electrical conductivity:

   • Pure water lacks ions → very low electrical conductivity → bad conductor of electricity

   • Conductivity increases if impurities or electrolytes are present

Other options:

• Acts as a solute: False; water is the solvent in most biological and chemical systems

• Good conductor: False; pure water is a poor conductor

• None of these: Incorrect

In de novo purine synthesis, the ribose sugar for the nucleotide is donated by phosphoribosyl pyrophosphate (PRPP).

• PRPP:

  • Synthesized from ribose-5-phosphate (from the pentose phosphate pathway)

  • Provides the ribose-phosphate backbone to which purine bases are attached to form IMP, AMP, GMP

Other options:

• Glutamine: Donates nitrogen atoms for purine ring

• Inosine monophosphate (IMP): Intermediate nucleotide, not a ribose donor

• Tetrahydrofolate: Donates one-carbon groups (formyl groups)

• Aspartate: Donates nitrogen and carbon in ring formation

Megaloblastic anemia is caused by impaired DNA synthesis, often due to defective nucleotide metabolism.

• Orotic aciduria:

  • Rare autosomal recessive disorder

  • Caused by deficiency of UMP synthase, an enzyme in de novo pyrimidine synthesis

  • Leads to accumulation of orotic acid and defective DNA synthesis → megaloblastic anemia

  • Not responsive to vitamin B12 or folate (distinguishing feature)

Other options:

• Lesch-Nyhan syndrome (LNS): Purine salvage defect → hyperuricemia, neurological symptoms, not anemia

• Hyperuricemia and gout: Result of purine degradation, unrelated to anemia

• Adenosine deaminase deficiency: Causes SCID, not megaloblastic anemia

Purine de novo synthesis occurs mainly in cells that have high proliferative and metabolic activity. Here’s the correct picture:

• Liver: Major site of de novo purine synthesis, producing nucleotides for the whole body. ✅

• Muscle: Has some limited capacity but mainly relies on salvage pathways; however, it can perform some de novo synthesis. ✅

• Brain: Cannot perform significant de novo purine synthesis; it depends almost entirely on the salvage pathway to recycle purine bases for nucleotides. ❌

Explanation

The brain lacks some of the enzymes required for the full de novo pathway, so it cannot synthesize purines from scratch. Instead, it salvages hypoxanthine and guanine via HGPRT and APRT to form nucleotides.

Answer: Brain

In most mammals (non-primate species), uric acid is further metabolized by the enzyme uricase (urate oxidase) into allantoin, a compound that is much more soluble in water and thus more easily excreted in urine.

The reaction is as follows:

Uric acid+O2+H2O→Allantoin+H2O2+CO2\text{Uric acid} + O_2 + H_2O → \text{Allantoin} + H_2O_2 + CO_2Uric acid+O2​+H2​O→Allantoin+H2​O2​+CO2​

Humans and higher primates lack the uricase enzyme, which is why uric acid remains the end product of purine metabolism and must be excreted directly. This evolutionary loss is associated with higher serum uric acid levels — beneficial as an antioxidant but also predisposing to gout when levels become excessive.

❌ Explanation of Incorrect Options

•  Glyoxylic acid:
  Involved in glycine and oxalate metabolism, not purine catabolism. It has no connection to uric acid breakdown.

•  Ammonia:
  Ammonia arises mainly from amino acid deamination, not from uric acid oxidation. Uric acid metabolism involves oxidative steps, not deamination.

•  Urea:
  Urea is produced in the urea cycle from ammonia and CO₂ — not from uric acid. The two processes are distinct: urea cycle handles nitrogen disposal, while uric acid metabolism handles purine degradation.

•  It is excreted directly in urine without being converted:
  This is true only for humans and higher primates, not for most mammals. Other mammals convert uric acid into allantoin before excretion.

During purine degradation:

1. Inosine monophosphate (IMP) and guanosine monophosphate (GMP) are nucleotides, which must first be converted to nucleosides.

2. 5′-nucleotidase removes the phosphate group from IMP and GMP → forming inosine and guanosine, respectively.

3. These nucleosides are then further broken down:

   • Inosine → hypoxanthine → xanthine → uric acid

   • Guanosine → guanine → xanthine → uric acid

Why the Other Options Are Incorrect:

• Guanylate kinase: Converts GMP → GDP (phosphorylation), not degradation.

• Adenosine deaminase: Acts on adenosine → inosine, not IMP or GMP.

• Ribonucleotide reductase: Converts ribonucleotides → deoxyribonucleotides, not degradation.

• Xanthine oxidase: Acts later in the pathway (xanthine → uric acid), not at the nucleotide-to-nucleoside step.

Lesch-Nyhan syndrome is a rare X-linked recessive disorder caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT).

• HGPRT is critical for the purine salvage pathway, which recycles hypoxanthine and guanine into IMP and GMP.

• Defect in HGPRT → purine bases cannot be salvaged → increased degradation of purines to uric acid → hyperuricemia.

• Clinical features:

  • Gout / uric acid stones

  • Neurological dysfunction (self-mutilation, dystonia)

  • Developmental delay

Why the Other Options Are Incorrect:

• Purine biosynthesis: De novo synthesis is unaffected.

• Purine degradation: Degradation is actually increased, not defective.

• Pyrimidine degradation / synthesis: Unrelated to Lesch-Nyhan syndrome.

Inosine monophosphate (IMP) is the branch-point intermediate in de novo purine synthesis.

• From IMP, two key purine nucleotides are synthesized:

  • Adenosine monophosphate (AMP)

  • Guanosine monophosphate (GMP)

Other options:

• Uric acid: End product of purine catabolism, not a precursor.

• Phosphoribosyl pyrophosphate (PRPP): Donates ribose-phosphate in the first step of purine synthesis but is not the immediate precursor of AMP/GMP.

• Glutamine: Nitrogen donor in purine synthesis, not a direct precursor.

• Orotate: Precursor in pyrimidine synthesis, not purines.

Glutamine is a key nitrogen donor in nucleotide synthesis:

• Purine synthesis: Donates nitrogen for positions N3 and N9 in the purine ring.

• Pyrimidine synthesis: Donates nitrogen for N3 of the pyrimidine ring.

Other amino acids contribute in a more limited or specific way:

• Aspartate: Nitrogen donor mainly in pyrimidine synthesis (N1).

• Glycine: Contributes nitrogen only in purine synthesis.

• Valine: Not involved in nucleotide nitrogen donation.

Thus, glutamine is unique in donating nitrogen to both purine and pyrimidine rings.

Xanthine oxidase is an enzyme involved in purine metabolism, converting hypoxanthine → xanthine → uric acid.

• Allopurinol is a structural analog of hypoxanthine and acts as a competitive inhibitor of xanthine oxidase.

• By inhibiting this enzyme, it reduces the production of uric acid, making it the drug of choice for conditions like gout and hyperuricemia (including tumor lysis syndrome).

Why the Other Options Are Incorrect:

• Mycophenolic acid – Inhibits inosine monophosphate dehydrogenase, blocking de novo guanine nucleotide synthesis (used as an immunosuppressant).

• 5-fluorouracil (5-FU) – Inhibits thymidylate synthase, interfering with pyrimidine synthesis.

• Methotrexate – Inhibits dihydrofolate reductase, blocking folate metabolism and purine/pyrimidine synthesis.

• Hydroxyurea – Inhibits ribonucleotide reductase, preventing DNA synthesis, often used in sickle cell disease.

In de novo purine synthesis, the purine ring is built atom by atom using specific amino acids and other molecules as nitrogen and carbon donors.

Sources of Nitrogen in Purine Synthesis:

• Glutamine → Provides nitrogen for N3 and N9 positions.

• Aspartate → Provides nitrogen for N1.

• Glycine → Contributes to the ring as part of N7 (and carbon skeleton too).

Alanine, however, does not contribute nitrogen to the purine ring.

Why the Other Options Are Incorrect

• Aspartate – Direct contributor to purine nitrogen.

• Glycine – Supplies nitrogen and carbon atoms.

• Glutamine – Important nitrogen donor in several steps.

• All of these are a source – Wrong because alanine is not a donor.

The first step in pyrimidine synthesis is the formation of carbamoyl phosphate, catalyzed by the enzyme carbamoyl phosphate synthetase II (CPS-II) in the cytosol.

Pathway overview:

1. Formation of carbamoyl phosphate – by CPS-II using glutamine, CO₂, and 2 ATP. ✅ (First and rate-limiting step)

2. Formation of carbamoyl aspartate – by aspartate transcarbamoylase.

3. Cyclization to form orotate.

4. Combination with PRPP to form orotidine monophosphate (OMP).

5. Conversion of OMP to UMP and eventually other pyrimidine nucleotides.

Why the Other Options Are Incorrect

• Formation of carbamoylaspartate: This is the second step, not the first.

• Formation of orotate: Happens later in the pathway after ring closure.

• Formation of PRPP: Belongs to purine and pyrimidine synthesis but is not the first committed step in pyrimidine synthesis.

• None of these: Incorrect because formation of carbamoyl phosphate is indeed the first step.

Carbamoyl phosphate synthetase II (CPS-II) is the rate-limiting enzyme of the de novo pyrimidine synthesis pathway.

• Location: Cytosol

• Function: Catalyzes the reaction:

  Glutamine + CO₂ + 2 ATP → Carbamoyl phosphateGlutamine + CO₂ + 2 ATP → Carbamoyl phosphate

Regulation:

• Activated by: PRPP (phosphoribosyl pyrophosphate) → promotes pyrimidine synthesis.

• Inhibited by: UTP (uridine triphosphate) → negative feedback to prevent excessive pyrimidine production.

Why the Other Options Are Incorrect

• UMP (Uridine monophosphate): Not a direct inhibitor; inhibition occurs mainly by UTP.

• PRPP: Activates, not inhibits, CPS-II.

• UDP (Uridine diphosphate): Intermediate but does not regulate CPS-II directly.

• ATP: Provides energy for the reaction but doesn’t regulate enzyme activity.

The end-product of purine metabolism in humans is uric acid.

• Purines such as adenine and guanine are broken down into xanthine and then converted into uric acid by the enzyme xanthine oxidase.

• Uric acid is excreted mainly by the kidneys in urine.

• Elevated levels can lead to gout due to deposition of monosodium urate crystals in joints.

Why the Other Options Are Incorrect

• Ammonia – Produced mainly from amino acid deamination, not from purine catabolism.

• Guanine – A purine base, but not the final product of its metabolism.

• Urea – End-product of protein/amino acid metabolism, formed in the urea cycle in the liver, not purine breakdown.

• Uracil – A pyrimidine base, not related to purine degradation.

The purine ring is built step by step on ribose-5-phosphate (via PRPP). Several amino acids contribute atoms:

• Aspartate → provides a nitrogen (N1).

• Glutamine → provides two nitrogens (N3, N9).

• Glycine → provides two carbons and a nitrogen (C4, C5, N7).

• Formyl-THF → provides carbons (C2, C8).

• CO₂ → provides one carbon (C6).

So both aspartate and glutamine are crucial in purine nucleotide biosynthesis.

Incorrect options:

• Triglyceride → made from glycerol + fatty acids, not amino acids.

• Ribose → comes from HMP shunt (not amino acids).

• Glucose → synthesized via gluconeogenesis, amino acids contribute carbons but not specifically aspartate + glutamine together.

• Cholesterol → made from acetyl-CoA, not amino acids.

The rate-limiting step of pyrimidine synthesis is catalyzed by the enzyme carbamoyl phosphate synthetase II (CPS-II), which produces carbamoyl phosphate in the cytosol. This enzyme is regulated by feedback inhibition from UTP and activation by PRPP, ensuring balanced nucleotide synthesis. Let’s break down why this is correct and why the other options are not:

• Formation of carbamoyl phosphate-2 (Correct):
  This step is catalyzed by CPS-II in the cytosol. It uses glutamine, CO₂, and ATP to form carbamoyl phosphate, which is the committed and rate-limiting step of pyrimidine synthesis. Its regulation is critical to control pyrimidine levels.

• Formation of phosphoribosyl pyrophosphate (PRPP):
  PRPP is important, but its synthesis is not specific to pyrimidines; it is used in both purine and pyrimidine pathways. While regulated, it is not the rate-limiting step for pyrimidine synthesis.

• Formation of orotate:
  Orotate is an intermediate formed later in the pathway, after carbamoylaspartate undergoes several reactions. It is not the committed or rate-limiting step.

• Formation of carbamoyl phosphate-1:
  This is catalyzed by CPS-I in the mitochondria, but it is used in the urea cycle, not in pyrimidine synthesis. So, this option is unrelated.

• Formation of carbamoylaspartate:
  This occurs after carbamoyl phosphate has already been formed (by CPS-II) and combined with aspartate. Although important, this is not the regulatory bottleneck of the pathway.

Arterial blood gas (ABG) analysis is a laboratory test used to assess the acid-base balance and respiratory function of a patient. It provides direct measurements of key parameters in arterial blood, which reflect oxygenation, ventilation, and acid-base status.

Parameters measured in ABG:

• pH → Indicates the acid-base status (acidosis or alkalosis).

• pCO2 (partial pressure of carbon dioxide) → Reflects the respiratory component of acid-base balance.

• pO2 (partial pressure of oxygen) → Indicates oxygenation of arterial blood.

• Oxygen saturation (SaO2) → Often calculated from pO2, sometimes measured directly with a co-oximeter.

Parameters not directly measured in ABG:

• Creatinine level → Kidney function marker, measured in serum chemistry, not in ABG.

• Anion gap → Calculated from serum electrolytes, not directly from ABG.

ABG is primarily about respiratory gases and acid-base balance, not metabolic waste products.

✅ Correct Answer: pH, pCO2 and pO2

❌ Why the other options are incorrect

• Anion gap → Calculated from electrolytes (Na⁺, K⁺, Cl⁻, HCO₃⁻), not directly from ABG.

• Oxygen saturation → Often derived from ABG or pulse oximetry, but ABG alone measures pO2 directly.

• Creatinine level → Blood chemistry, unrelated to ABG.

• pCO2 and pO2 → Partial answer; ABG also measures pH, which is crucial for acid-base assessment.

Xanthine oxidase is a molybdenum-containing enzyme found mainly in the liver and intestinal mucosa. It catalyzes two sequential oxidative reactions in purine degradation:

1. Hypoxanthine → Xanthine

2. Xanthine → Uric Acid

During these oxidations, molecular oxygen (O₂) acts as the terminal electron acceptor. For every molecule of xanthine oxidized, one molecule of oxygen is reduced to hydrogen peroxide (H₂O₂).
Hence, uric acid and hydrogen peroxide are the final products of this reaction.

The production of H₂O₂ is clinically significant because excessive activity of xanthine oxidase can lead to oxidative stress, contributing to tissue injury during ischemia-reperfusion and inflammatory conditions.

❌ Explanation of Incorrect Options

•  H₂O:
  Water is not a product in this oxidation step. Instead, O₂ is reduced to H₂O₂, not to H₂O. Water formation would occur only if additional enzymatic systems like catalase or peroxidase further reduce H₂O₂.

•  HCO₃⁻:
  Bicarbonate is unrelated to purine degradation. It’s part of the acid–base buffering system in blood and does not participate in xanthine metabolism.

•  CO₂:
  No decarboxylation occurs in the xanthine → uric acid conversion, so CO₂ is not released. Carbon dioxide is produced in other catabolic reactions but not in purine oxidation.

•  O₂:
  Oxygen is a substrate, not a product. It is consumed by xanthine oxidase to form reactive oxygen species (ROS), including H₂O₂ and superoxide (O₂⁻).

✅ Correct Answer: Carbamoyl phosphate synthase II

Explanation:

Step 1: Pyrimidine biosynthesis overview

• Pyrimidine nucleotides (CTP, UTP, TMP) are synthesized de novo in mammalian cells.

• The first committed step is the formation of carbamoyl phosphate from glutamine, CO₂, and ATP, catalyzed by carbamoyl phosphate synthase II (CPS II).

• This is the rate-limiting step in the pathway.

Step 2: Regulation

• CPS II is allosterically inhibited by UTP and activated by PRPP.

• Its activity determines the overall rate of pyrimidine synthesis in the cell.

Step 3: Cellular location

• CPS II is cytosolic, unlike CPS I, which is mitochondrial and involved in the urea cycle.

❌ Why the other options are incorrect:

Thymidylate synthase

• ❌ Catalyzes the conversion of dUMP to dTMP, a later step in pyrimidine metabolism, not the rate-limiting step.

Aspartate transcarbamoylase

• ❌ Catalyzes the reaction of carbamoyl phosphate with aspartate, forming carbamoyl aspartate, a subsequent step, not rate-limiting in mammalian cells (rate-limiting in bacteria).

Xanthine oxidase

• ❌ Involved in purine degradation, not pyrimidine biosynthesis.

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)

• ❌ Involved in purine salvage pathway, not pyrimidine biosynthesis.

✅ Correct Answer: Reabsorption of bicarbonate ion

Explanation:

Step 1: Role of the proximal tubule in acid-base balance

• The proximal tubule reabsorbs about 80–90% of filtered bicarbonate (HCO3⁻).

• Bicarbonate is not directly transported; instead, H⁺ ions are secreted into the tubular lumen, where they combine with filtered bicarbonate to form carbonic acid (H2CO3).

• Carbonic acid is converted to CO2 and water by carbonic anhydrase, which diffuse back into tubular cells, regenerate bicarbonate, and enter the blood.

Step 2: Key point

• Therefore, the secretion of H⁺ in the proximal tubule is primarily linked to the reabsorption of bicarbonate.

• This mechanism is crucial for maintaining systemic acid-base balance.

❌ Why the other options are incorrect:

Excretion of hydrogen ion

• ❌ H⁺ excretion is the result, but the main physiological driver is bicarbonate reabsorption.

Reabsorption of calcium ion

• ❌ Calcium reabsorption is mostly passive, linked to sodium and water reabsorption, not H⁺ secretion.

Excretion of potassium ion

• ❌ Potassium secretion mainly occurs in the distal tubule and collecting duct, not proximal H⁺ secretion.

Reabsorption of phosphate ion

• ❌ Phosphate acts as a buffer for H⁺ in the tubular lumen, but H⁺ secretion is mainly tied to bicarbonate, not phosphate reabsorption.

✅ Correct Answer: Uric acid

Explanation:

Step 1: Purine metabolism overview

• Purines (adenine and guanine) are broken down in several steps:

  • Adenine → inosine → hypoxanthine

  • Guanine → guanosine → xanthine

• Hypoxanthine and xanthine are then oxidized by xanthine oxidase to form uric acid.

Step 2: Excretion

• Humans cannot further degrade uric acid to allantoin (unlike many other mammals) due to the lack of uricase.

• Uric acid is therefore the final excreted product of purine metabolism in humans.

Step 3: Clinical relevance

• Excess uric acid can lead to gout or urate kidney stones.

❌ Why the other options are incorrect:

Hypoxanthine

• ❌ Intermediate in purine degradation, not the final product.

Urea

• ❌ Product of amino acid metabolism, not purine metabolism.

Xanthine

• ❌ Intermediate in purine breakdown, converted to uric acid by xanthine oxidase.

Inositol

• ❌ A sugar alcohol, unrelated to purine metabolism.

✅ Correct Answer: Increase in plasma bicarbonate (HCO₃⁻) concentration

Explanation:

Step 1: Pathophysiology of respiratory acidosis

• Respiratory acidosis occurs due to hypoventilation, leading to increased PCO₂.

• Elevated CO₂ increases H⁺ concentration via the reaction:

CO2+H2O⇌H2CO3⇌H++HCO3−CO2​+H2​O⇌H2​CO3​⇌H++HCO3−​

Step 2: Renal compensation

• The kidneys compensate over hours to days by:

  • Increasing reabsorption of HCO₃⁻ in proximal tubules

  • Increasing H⁺ excretion (as NH₄⁺ or titratable acids)

• This raises plasma bicarbonate, buffering the excess H⁺ and partially normalizing pH.

Step 3: Clinical relevance

• Chronic respiratory acidosis (e.g., COPD) is characterized by elevated plasma HCO₃⁻ as a compensatory mechanism.

❌ Why the other options are incorrect:

Decrease in plasma bicarbonate (HCO₃⁻) concentration

• ❌ Would worsen acidosis instead of compensating.

Increased oxygen saturation

• ❌ Not a compensatory mechanism for CO₂ retention; hypoventilation often reduces O₂ saturation.

Decreased levels of ammonia

• ❌ Renal compensation increases NH₃/NH₄⁺ excretion, not decreases it.

Decreased respiratory rate

• ❌ Would increase CO₂ further, worsening acidosis; not compensatory.

✅ Correct Answer: Acidosis

Explanation:

Step 1: Relationship between potassium and acid-base balance

• In the distal nephron, K+ and H+ are exchanged for sodium in the principal and intercalated cells.

• Hyperkalemia (high plasma K+) inhibits renal H+ secretion, because H+ secretion is coupled with K+ uptake.

• Result: less H+ excretion → retention of H+ → metabolic acidosis.

Step 2: Mechanism during renal correction

• As the kidney corrects hyperkalemia, H+ secretion is reduced, so plasma becomes more acidic.

• Conversely, hypokalemia promotes H+ secretion → alkalosis.

❌ Why the other options are incorrect:

Increased secretion of H+

• ❌ Hyperkalemia reduces H+ secretion, not increases it.

Alkalosis

• ❌ Hyperkalemia favors acidosis, not alkalosis.

Increased secretion of Na+

• ❌ Sodium reabsorption is not the primary compensatory mechanism for acute hyperkalemia.

Increased secretion of HCO3-

• ❌ Hyperkalemia does not increase bicarbonate secretion; bicarbonate retention may occur to balance charge.

The rate-limiting step of pyrimidine biosynthesis in mammalian cells is catalyzed by carbamoyl phosphate synthase II (CPS II).

• CPS II is located in the cytosol (unlike CPS I in mitochondria, which is part of the urea cycle).

• It catalyzes the reaction:
  Glutamine + CO₂ + 2 ATP → Carbamoyl phosphate

• This carbamoyl phosphate then combines with aspartate (via aspartate transcarbamoylase) to form carbamoyl aspartate, which eventually leads to the synthesis of orotic acid and then UMP.

• Since CPS II is tightly regulated (inhibited by UTP and activated by PRPP and ATP), it is considered the rate-limiting enzyme for pyrimidine biosynthesis.

Why the Other Options Are Incorrect

• Thymidylate synthase ❌
  Converts dUMP to dTMP in DNA synthesis, but this is not the rate-limiting step of pyrimidine biosynthesis.

• Aspartate transcarbamoylase ❌
  Catalyzes the second step (carbamoyl phosphate + aspartate → carbamoyl aspartate). Important, but not rate-limiting in mammalian cells (though it is rate-limiting in bacteria).

• Xanthine oxidase ❌
  Involved in purine degradation (converting hypoxanthine → xanthine → uric acid), not in pyrimidine synthesis.

• Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) ❌
  Part of the purine salvage pathway, deficiency of which causes Lesch–Nyhan syndrome, not related to pyrimidine biosynthesis.

✅ Correct Answer: H⁺ ions

Explanation:

Step 1: Sodium reabsorption mechanism

• In the proximal tubule, sodium reabsorption is a key process for fluid and electrolyte balance.

• One of the main mechanisms is the Na⁺/H⁺ exchanger:

  • Na⁺ is transported from the tubular lumen into the tubular cell.

  • H⁺ is secreted into the lumen in exchange.

• This process allows sodium reabsorption while facilitating acid excretion and bicarbonate reabsorption.

Step 2: Physiological relevance

• Helps maintain acid-base balance.

• Supports secondary active transport of other substances (glucose, amino acids) that depend on the sodium gradient.

❌ Why the other options are incorrect:

Na⁺ ions

• Sodium does not exchange with itself; it is the ion being reabsorbed.

HCO3⁻ ions

• Bicarbonate is reabsorbed indirectly via H⁺ secretion, not directly exchanged with sodium.

K⁺ ions

• Sodium-potassium exchange occurs mainly in the distal tubule and collecting duct, not the primary proximal tubular sodium reabsorption.

Cl⁻ ions

• Chloride follows sodium passively to maintain electroneutrality, not via direct exchange.

✅ Correct Answer: Raised PCO2

Explanation:

Step 1: Role of PCO2 in bicarbonate reabsorption

• CO2 diffuses into renal tubular cells from the blood.

• Inside the cell, CO2 reacts with water (via carbonic anhydrase) to form H2CO3, which dissociates into H⁺ and HCO3⁻.

• H⁺ is secreted into the tubular lumen, and HCO3⁻ is reabsorbed into the blood.

• Therefore, elevated PCO2 increases H⁺ formation, enhancing bicarbonate reabsorption.

Step 2: Physiological context

• Seen in respiratory acidosis: high CO2 stimulates renal compensation by increasing HCO3⁻ reabsorption.

❌ Why the other options are incorrect:

Retention of acid metabolites

• Acid retention indirectly increases HCO3⁻, but the immediate trigger in renal cells is CO2.

Low acid secretion

• Would reduce H⁺ availability and decrease bicarbonate reabsorption.

Decreased NH3 formation

• NH3 helps excrete H⁺ as NH4⁺; decreased NH3 reduces acid excretion, not bicarbonate reabsorption.

Decreased PCO2

• Hypocapnia lowers intracellular H⁺ formation and reduces bicarbonate reabsorption.

✅ Correct Answer: Urea

Explanation:

Step 1: Role of carbamoyl phosphate

• Carbamoyl phosphate is formed from ammonia and bicarbonate in the mitochondria of liver cells by carbamoyl phosphate synthetase I.

• It is the first step in the urea cycle, which is responsible for detoxifying ammonia by converting it to urea.

Step 2: Pathway summary

• Ammonia + CO₂ → Carbamoyl phosphate → Urea

• Urea is then transported to the kidney for excretion in urine.

❌ Why the other options are incorrect:

Xanthine / Hypoxanthine / Ionosine / Uric acid

• These are products of purine metabolism, not the urea cycle.

• Carbamoyl phosphate for purine synthesis is a different form (cytosolic, carbamoyl phosphate synthetase II), which contributes to pyrimidine, not purine, synthesis.

✅ Correct Answer: Plasma pH and increased plasma bicarbonate (HCO3-) levels

Explanation:

Step 1: Definition of metabolic alkalosis

• Metabolic alkalosis is a primary increase in plasma bicarbonate (HCO3-) that leads to an elevated blood pH (>7.45).

Step 2: Mechanism

• Causes include:

  • Loss of hydrogen ions (vomiting, gastric suction)

  • Excess bicarbonate intake (antacids, IV bicarbonate)

  • Diuretic use (causing H+ loss in urine)

• The increase in HCO3- shifts the buffer equilibrium, raising pH.

Step 3: Compensation

• Respiratory system compensates via hypoventilation to retain CO2 and partially correct pH.

❌ Why the other options are incorrect:

Plasma pH and increased lactate levels

• Increased lactate is associated with metabolic acidosis, not alkalosis.

Plasma pH and decreased CO2 levels

• Decreased CO2 is a respiratory alkalosis compensation or primary disorder.

Plasma pH and increased respiratory rate

• Increased respiratory rate occurs in metabolic acidosis to blow off CO2; in alkalosis, respiratory rate usually decreases.

Plasma pH and decrease in HCO3- levels

• Decreased HCO3- is characteristic of metabolic acidosis, not alkalosis.

✅ Correct Answer: Xanthine

Explanation:

Step 1: Purine degradation pathway

• Guanine is a purine base found in nucleotides like GMP.

• During catabolism:

  1. Guanine undergoes deamination (removal of an amino group).

  2. This reaction is catalyzed by guanine deaminase.

  3. The product is xanthine, which is further oxidized by xanthine oxidase to uric acid, the end product excreted in urine.

Step 2: Summary

• Guanine → Xanthine → Uric acid

• This is a key step in purine nucleotide breakdown.

❌ Why the other options are incorrect:

Cytidylic acid

• This is a pyrimidine nucleotide, unrelated to guanine catabolism.

Uracil

• Pyrimidine base; produced from cytidine or thymine, not guanine.

Methyl guanine

• A modified nucleotide, not a normal catabolic product of guanine.

Thiamine

• Vitamin B1, unrelated to purine metabolism.

The de novo synthesis pathways for purines and pyrimidines are distinct but share key common substrates. The compound “glutamine, carbon dioxide, and aspartate” refers to carbamoyl phosphate, a critical intermediate synthesized by carbamoyl phosphate synthetase II (CPS II) in the pyrimidine pathway. However, let’s break down the roles of these molecules in both pathways:

1. Glutamine:
   • Purines: Donates its amide nitrogen at two steps (N3 and N9 positions of the purine ring).
   • Pyrimidines: Donates its amide nitrogen for the synthesis of carbamoyl phosphate (via CPS II) and also for the conversion of UTP to CTP.
2. Carbon Dioxide (CO₂):
   • Purines: Incorporated as the C6 carbon of the purine ring.
   • Pyrimidines: Incorporated as the C2 carbon of the pyrimidine ring during carbamoyl phosphate synthesis.
3. Aspartate:
   • Purines: Provides the N1 atom of the purine ring.
   • Pyrimidines: Provides the entire pyrimidine ring backbone (aspartate + carbamoyl phosphate → orotic acid) and the nitrogen for CTP synthesis.

Thus, all three—glutamine, CO₂, and aspartate—are directly involved in building both purine and pyrimidine rings.

Why the Other Options Are Incorrect:

❌ Tetrahydrofolate (THF):

• • THF is crucial for purine synthesis (donates formyl groups for C2 and C8 positions) and thymidylate (dTMP) synthesis in pyrimidine metabolism. However, it is not involved in the initial ring construction of pyrimidines (uracil, cytosine). Thus, it is not common to both pathways for ring formation.

    ❌ Aspartate (alone):

    • While aspartate is used in both pathways (as explained above), the question asks for the option that best captures the common contributors. “Aspartate alone” is incomplete because glutamine and CO₂ are equally critical for both pathways.

      ❌ Glutamine (alone):

      • Glutamine is a key nitrogen donor in both pathways, but CO₂ and aspartate are also essential. Using glutamine alone ignores the roles of CO₂ (carbon source) and aspartate (carbon/nitrogen source).

        ❌ Glycine:

        • Glycine is incorporated entirely into the purine ring (as C4, C5, and N7). It plays no role in pyrimidine synthesis.

• The pyrimidine ring (cytosine, thymine, uracil) is assembled from carbamoyl phosphate and aspartate.

• The contributions are:

  • Aspartate → contributes three atoms to the ring (N1, C4, C5, C6).

  • Glutamine → donates the nitrogen used by CPS II to form carbamoyl phosphate.

  • Carbon dioxide (CO₂) → contributes one carbon atom to the carbamoyl phosphate, which becomes part of the pyrimidine ring.

• Tetrahydrofolate (THF) is used in purine synthesis (donates C1 units at positions C2 and C8 of the purine ring), not pyrimidines.

• Glycine contributes to purine ring synthesis (providing N7, C4, C5), not pyrimidines.

• Glutamate is a nitrogen donor in other reactions but not directly in the pyrimidine ring skeleton.

Thus, the single carbon atom in the pyrimidine ring comes from carbon dioxide.

✅ Correct Answer: Protein and glucose

Explanation:

Step 1: Understanding the dipstick test

• A urine dipstick is a chemical test strip with pads that change color based on specific substances in the urine.

• It rapidly screens for:

  • Protein (albumin) – indicates kidney disease or glomerular damage.

  • Glucose – indicates glycosuria, often due to diabetes mellitus.

  • Ketones, blood, bilirubin, pH, nitrite, leukocyte esterase, etc.

Step 2: Mechanism

• Each pad contains reagents that react with a specific analyte, producing a color change that is semi-quantitative.

• It does not identify cells, casts, crystals, or organisms.

❌ Why the other options are incorrect:

Infecting organism

• Requires microscopy or culture, not detected by dipstick.

Casts

• Detected by microscopic examination, not dipstick.

Crystals

• Also require microscopy, not chemical dipstick test.

Cells

• WBCs or RBCs are confirmed by microscopy, though dipstick may suggest blood or leukocyte esterase presence.

✅ Correct Answer: Secretion of HCO₃⁻ ions

Explanation:

Step 1: Role of kidneys in acid-base balance

• The kidneys maintain plasma pH by:

  • Reabsorbing bicarbonate (HCO₃⁻) when plasma is acidic.

  • Excreting H⁺ ions into urine.

  • Adjusting HCO₃⁻ excretion in response to alkalosis.

Step 2: Response to alkalosis

• In metabolic or respiratory alkalosis, plasma pH is elevated.

• The kidneys compensate by increasing HCO₃⁻ excretion in urine.

• This reduces plasma bicarbonate levels, helping bring pH back to normal.

Step 3: Mechanism

• Distal tubules and collecting ducts secrete bicarbonate in exchange for chloride ions.

• This increases urine alkalinity and lowers plasma bicarbonate.

❌ Why the other options are incorrect:

Nitrogen retention

• Not a primary mechanism for acid-base balance.

Secretion of H⁺ ions

• Would worsen alkalosis; H⁺ secretion occurs in acidosis.

Secretion of Na⁺ ions

• Independent of acid-base status; mainly regulated by volume and aldosterone.

Secretion of K⁺ ions

• K⁺ handling is influenced indirectly, but not the primary response to alkalosis.

✅ Correct Answer: Secretion of H⁺ ions

Explanation:

Step 1: Role of the kidneys in acid-base balance

• The kidneys regulate long-term acid-base balance by:

  • Reabsorbing bicarbonate (HCO₃⁻) from the filtrate.

  • Excreting hydrogen ions (H⁺) into the urine.

  • Generating new bicarbonate for the plasma.

Step 2: Response to acidosis

• In metabolic acidosis or high plasma H⁺:

  • H⁺ secretion by tubular cells increases, mainly in the proximal and distal tubules.

  • This helps acidify urine and restore normal plasma pH.

Step 3: Other mechanisms

• H⁺ combines with buffer ions (phosphate, ammonia) to be excreted safely.

❌ Why the other options are incorrect:

Secretion of HCO₃⁻ ions

• The kidneys reabsorb or generate HCO₃⁻, not secrete it, in acidosis.

Nitrogen retention

• Nitrogen retention is not a primary renal response to acidosis.

Secretion of Na⁺ ions

• Na⁺ excretion is independent of acidosis; it is more related to volume and electrolyte balance.

Secretion of K⁺ ions

• K⁺ handling may be affected indirectly, but primary response to acidosis is H⁺ secretion.

✅ Correct Answer: Paradoxical aciduria

Explanation:

Step 1: Definition

• Paradoxical aciduria occurs when the blood or extracellular fluid is alkaline, but the urine remains acidic.

• This seems “paradoxical” because normally, urine pH tends to mirror systemic acid-base status.

Step 2: Mechanism

• Commonly seen in conditions like volume depletion:

  • Extracellular fluid is depleted, leading to aldosterone-mediated H⁺ secretion in the distal nephron.

  • Even if the plasma is slightly alkaline, the kidney continues to excrete H⁺, making urine acidic.

Step 3: Clinical significance

• Helps differentiate types of renal tubular disorders or volume depletion states.

❌ Why the other options are incorrect:

Phenylketonuria

• Inherited metabolic disorder causing phenylalanine accumulation; unrelated to urine acidity.

Aminoaciduria

• Presence of amino acids in urine; not related to paradoxical urine pH.

Glucosuria

• Glucose in urine; associated with hyperglycemia or tubular defects, not urine alkalinity/acid-base mismatch.

Ketonuria

• Ketone bodies in urine; seen in diabetes or starvation, not specifically linked to paradoxical urine pH.

✅ Correct Answer: Ringer’s lactate

Explanation:

Step 1: Assess the patient’s condition

• Moderate dehydration → loss of water and electrolytes.

• Oral intake not possible → requires intravenous fluid replacement.

• Normal renal function → patient can handle isotonic fluids.

Step 2: Fluid selection principles

• Goal: restore extracellular fluid volume safely and replace electrolytes.

• Ringer’s lactate is an isotonic crystalloid:

  • Electrolyte composition similar to plasma (Na⁺, K⁺, Ca²⁺, Cl⁻, lactate).

  • Rapidly restores intravascular volume without causing shifts in osmolality.

• Safe to give in moderate dehydration with normal renal function.

Step 3: Why other fluids are not ideal initially

• 3% saline → hypertonic; used only for severe symptomatic hyponatremia, not routine dehydration.

• Distilled water → hypotonic; can cause hemolysis or cerebral edema if given IV.

• 1/3 saline (0.33% NaCl) → hypotonic; could worsen intravascular volume deficit initially.

• 5% dextrose → isotonic in bag but effectively hypotonic in body after metabolism; does not replace electrolytes effectively for dehydration.

❌ Why the other options are incorrect:

3% saline

• Hypertonic; risk of central pontine myelinolysis if infused too rapidly.

Distilled water

• Pure water; risk of cell lysis and hyponatremia.

1/3 saline

• Hypotonic; not suitable for initial volume resuscitation.

5% dextrose

• Provides water and calories, but minimal electrolytes; not ideal for moderate dehydration with electrolyte loss.

✅ Correct Answer: Dipolar

Explanation:

Step 1: Structure of water (H₂O)

• Water has two hydrogen atoms covalently bonded to one oxygen atom.

• Oxygen is more electronegative, so it pulls electrons toward itself, creating a partial negative charge (δ⁻) on oxygen and partial positive charges (δ⁺) on the hydrogens.

Step 2: Polarity concept

• Because of the bent shape (~104.5°), the charge distribution is asymmetrical.

• This creates a molecule with a positive end and a negative end, known as a dipole.

Step 3: Implications

• Dipolar nature allows water to form hydrogen bonds, dissolve polar substances, and have high cohesion and surface tension.

❌ Why the other options are incorrect:

Pentapolar

• No molecule has five poles; water has only two effective charge centers.

Unipolar

• Would have a single net charge; water is neutral overall, just polar.

Tripolar

• Incorrect; water has two poles (positive and negative).

Tetrapolar

• Incorrect; water only has one negative pole and one positive pole.

✅ Correct Answer: Hypoxanthine

Explanation:

Step 1: Mechanism of action of allopurinol

• Allopurinol is used to treat hyperuricemia and gout by inhibiting xanthine oxidase, the enzyme that converts hypoxanthine → xanthine → uric acid.

• Structurally, allopurinol resembles hypoxanthine, which allows it to bind xanthine oxidase and act as a competitive inhibitor.

• This leads to decreased production of uric acid and accumulation of more soluble precursors (hypoxanthine and xanthine), which are excreted in urine.

Step 2: Clinical relevance

• Allopurinol is commonly used in patients with gout, tumor lysis syndrome, and hyperuricemia due to chemotherapy.

❌ Why the other options are incorrect:

Cytosine

• A pyrimidine base.

• Not structurally similar to purine bases, so allopurinol is not an analog.

Orotic acid

• Pyrimidine precursor involved in UMP synthesis.

• Not targeted by xanthine oxidase.

Thymine

• Pyrimidine base in DNA.

• No structural similarity to hypoxanthine.

Inosine

• A nucleoside (hypoxanthine + ribose).

• Allopurinol is an analog of the base, not the nucleoside.

✅ Correct Answer: Oxaloacetate

Explanation:

Step 1: Understanding aspartate metabolism

• Aspartate is an amino acid that can be converted into a TCA cycle intermediate through a transamination reaction.

• The enzyme aspartate aminotransferase (AST) catalyzes the transfer of the amino group from aspartate to α-ketoglutarate, forming oxaloacetate and glutamate:

Aspartate + α-ketoglutarate → Oxaloacetate + GlutamateAspartate + α-ketoglutarate → Oxaloacetate + Glutamate

Step 2: Role in TCA cycle

• Oxaloacetate is a key TCA cycle intermediate that condenses with acetyl-CoA to form citrate, initiating the cycle.

• By entering as oxaloacetate, aspartate contributes to the anaplerotic replenishment of TCA cycle intermediates.

Key point: Aspartate does not directly become succinate, alpha-ketoglutarate, citrate, or fumarate; it specifically forms oxaloacetate, which integrates into the cycle.

❌ Why the other options are incorrect:

Succinic acid

• Succinic acid (succinate) is an intermediate formed later in the TCA cycle from succinyl-CoA.

• Aspartate is not converted directly to succinate.

Alpha-ketoglutarate

• α-Ketoglutarate can accept an amino group from aspartate transamination, but aspartate itself does not become α-ketoglutarate.

Citrate

• Citrate is formed from oxaloacetate + acetyl-CoA in the first step of the TCA cycle.

• Aspartate is upstream and does not directly form citrate.

Fumarate

• Fumarate is generated later in the cycle from succinate.

• Aspartate conversion to oxaloacetate occurs before fumarate formation.

✅ Correct Answer: 5′-nucleotidase

Explanation:

Purine nucleotide catabolism involves several enzymatic steps to ultimately produce uric acid.

Stepwise breakdown:

1. IMP (inosine monophosphate) → inosine

2. GMP (guanosine monophosphate) → guanosine

These reactions are catalyzed by 5′-nucleotidase, which removes the phosphate group from the nucleotide to form the corresponding nucleoside.

Next steps:

• Inosine → hypoxanthine (by nucleoside phosphorylase)

• Guanosine → guanine (by nucleoside phosphorylase)

• Guanine → xanthine (by guanine deaminase)

• Hypoxanthine → xanthine → uric acid (both by xanthine oxidase)

Key point: The first step in purine degradation involves removing the phosphate group, which is why 5′-nucleotidase is the correct enzyme for IMP and GMP breakdown.

❌ Why the other options are incorrect:

Ribonucleotide reductase

• Converts ribonucleotides to deoxyribonucleotides for DNA synthesis.

• Not involved in purine degradation.

Adenosine deaminase

• Converts adenosine to inosine.

• Specific to adenosine; does not act on IMP or GMP directly.

Xanthine oxidase

• Catalyzes the final steps: hypoxanthine → xanthine → uric acid.

• Acts after nucleosides are formed, not on IMP or GMP directly.

Guanylate kinase

• Converts GMP to GDP, part of nucleotide phosphorylation, not degradation.

Glutamine, carbon dioxide, and aspartate (Correct) ✅

• Pyrimidine synthesis begins with carbamoyl phosphate, formed by carbamoyl phosphate synthetase II (CPS II) in the cytosol.

• CPS II uses glutamine (as nitrogen donor) and CO₂ (as carbon source).

• Later, aspartate combines with carbamoyl phosphate to form carbamoyl aspartate, the first committed step toward pyrimidines.

• Thus, all three — glutamine, CO₂, and aspartate — are essential.

Glutamine and aspartate ❌

• Partially correct, but incomplete — carbon dioxide is also required.

Aspartate only ❌

• Aspartate is necessary (contributes atoms to the pyrimidine ring), but cannot form pyrimidines on its own.

NADH only ❌

• NADH is important in general metabolism but is not a building block in pyrimidine synthesis.

Glutamine and NADH ❌

• Again, NADH is irrelevant here. Carbon dioxide and aspartate are missing, making this option wrong.

Concept Recap

• Cytosine is one of the DNA bases (a pyrimidine).

• Deamination = removal of an amino (–NH₂) group from a molecule.

• When cytosine undergoes deamination, the amino group at position 4 is replaced with a keto group (C=O).

• This chemical change converts cytosine → uracil.

Correct Answer: Uracil ✅

Why not the other options?

1. Adenine ❌

   • Adenine is a purine base, not derived from deamination of cytosine.

2. Methyl cytosine ❌

   • That’s formed by methylation (addition of –CH₃), not deamination.

3. Cytidylic acid ❌

   • That’s a nucleotide (cytosine + ribose + phosphate), not a product of deamination.

4. Tyrosine ❌

   • Tyrosine is an amino acid, completely unrelated to pyrimidine metabolism.

Key Takeaway

• Spontaneous deamination of cytosine → uracil

• This is mutagenic: uracil pairs with adenine, leading to a C:G → T:A transition mutation if not repaired.

• Allopurinol is a structural analog of hypoxanthine, a natural purine base.

• After administration, allopurinol is converted to oxypurinol (alloxanthine), which strongly inhibits xanthine oxidase, the enzyme responsible for converting hypoxanthine → xanthine → uric acid.

• By inhibiting this pathway, allopurinol lowers uric acid production, making it a cornerstone in the management of gout and hyperuricemia.

Why Other Options Are Wrong

• Uric acid ❌ – Allopurinol decreases uric acid production but is not a structural analog of it.

• Xanthine oxidase ❌ – This is the enzyme target, not the structural analog.

• Inosine monophosphate (IMP) ❌ – Intermediate in purine nucleotide metabolism, unrelated structurally.

• Phosphoribosyl pyrophosphate (PRPP) ❌ – A ribose-phosphate donor in nucleotide synthesis, not structurally similar to allopurinol.