A 7-day-old boy of consanguineous parents feeds poorly, is lethargic and has a sweet, burnt-sugar odour. Glucose 70 mg/dL, urine ketones 2+, and urine gives a yellow precipitate with 2,4-dinitrophenylhydrazine. Plasma leucine, isoleucine and valine are raised and alloisoleucine is present. Which enzyme is defective?

Branched-chain alpha-keto acid dehydrogenase

According to a widely taught explanation, why is a high ammonia level toxic to the brain? Because ammonia:

Depletes alpha-ketoglutarate and slows the TCA cycle

Binds haemoglobin and reduces oxygen delivery

Raises blood pH enough to stop glycolysis

Inhibits carbamoyl phosphate synthetase I in neurons

Which urea cycle enzyme needs N-acetylglutamate as an essential activator and sets the rate of the whole cycle?

Carbamoyl phosphate synthetase I

Ornithine transcarbamoylase (OTC)

Why is a newborn blood spot for phenylketonuria screening collected only after 24 to 48 hours of milk feeding?

Phenylalanine rises only after protein feeding begins

Phenylpyruvate takes days to enter the blood

Maternal phenylalanine hydroxylase lasts a week

Heel-prick blood is unreliable before 24 hours

Daily urinary creatinine output stays nearly constant for a given person because creatinine:

Forms non-enzymatically from muscle creatine phosphate

Is made by the liver at a fixed hourly rate

Is reabsorbed by the renal tubules to keep levels steady

Comes mainly from the protein in dietary meat

Protein and amino acid metabolism, NPN and inborn errors

58 Kerala MSc MLT Entrance practice questions on Protein and amino acid metabolism, NPN and inborn errors, part of Biochemistry. The first 25 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

Question 1 · Hard
A 7-day-old boy of consanguineous parents feeds poorly, is lethargic and has a sweet, burnt-sugar odour. Glucose 70 mg/dL, urine ketones 2+, and urine gives a yellow precipitate with 2,4-dinitrophenylhydrazine. Plasma leucine, isoleucine and valine are raised and alloisoleucine is present. Which enzyme is defective?
1. ABranched-chain alpha-keto acid dehydrogenase
2. BPhenylalanine hydroxylase
3. CPropionyl-CoA carboxylase
4. DFumarylacetoacetate hydrolase
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Answer: A · Branched-chain alpha-keto acid dehydrogenase
The odour, ketosis and a positive DNPH test (which detects alpha-keto acids) suggest maple syrup urine disease. Raised leucine, isoleucine and valine with alloisoleucine confirm it, as alloisoleucine is specific for MSUD. The defect is in the mitochondrial branched-chain alpha-keto acid dehydrogenase complex, which needs thiamine pyrophosphate. Leucine is the most neurotoxic of the three.
- B: PKU raises phenylalanine and does not cause a neonatal ketotic crisis.
- C: Propionic acidaemia does not raise the branched-chain amino acids or alloisoleucine.
- D: Fumarylacetoacetate hydrolase deficiency (tyrosinaemia type 1) raises tyrosine and succinylacetone.
Question 2 · Medium
According to a widely taught explanation, why is a high ammonia level toxic to the brain? Because ammonia:
1. ADepletes alpha-ketoglutarate and slows the TCA cycle
2. BBinds haemoglobin and reduces oxygen delivery
3. CRaises blood pH enough to stop glycolysis
4. DInhibits carbamoyl phosphate synthetase I in neurons
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Answer: A · Depletes alpha-ketoglutarate and slows the TCA cycle
The brain removes ammonia by converting alpha-ketoglutarate to glutamate and glutamate to glutamine. With excess ammonia this drains alpha-ketoglutarate from the TCA cycle, so neuronal ATP production falls. Glutamine also builds up in astrocytes and draws in water, causing swelling. The result is the confusion and coma of hyperammonaemia.
- B: Ammonia does not bind haemoglobin.
- C: Hyperammonaemia causes a mild respiratory alkalosis, not a pH that stops glycolysis.
- D: Neurons have no functional urea cycle, so this is not the mechanism.
Question 3 · Easy
Which urea cycle enzyme needs N-acetylglutamate as an essential activator and sets the rate of the whole cycle?
1. AArginase
2. BCarbamoyl phosphate synthetase I
3. COrnithine transcarbamoylase (OTC)
4. DArgininosuccinate synthetase
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Answer: B · Carbamoyl phosphate synthetase I
Carbamoyl phosphate synthetase I, in liver mitochondria, joins ammonia, bicarbonate and ATP to form carbamoyl phosphate. It is inactive without N-acetylglutamate, which rises after a protein meal, so it controls the flux through the cycle. A deficiency of N-acetylglutamate synthase therefore mimics CPS I deficiency. The other enzymes act later in the cycle and are not the control point.
- A: Arginase releases urea at the end of the cycle and is not rate-limiting.
- C: OTC adds carbamoyl phosphate to ornithine but needs no N-acetylglutamate.
- D: Argininosuccinate synthetase adds aspartate and is not the regulated step.
Question 4 · Medium
Why is a newborn blood spot for phenylketonuria screening collected only after 24 to 48 hours of milk feeding?
1. APhenylpyruvate takes days to enter the blood
2. BPhenylalanine rises only after protein feeding begins
3. CMaternal phenylalanine hydroxylase lasts a week
4. DHeel-prick blood is unreliable before 24 hours
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Answer: B · Phenylalanine rises only after protein feeding begins
Before birth, excess phenylalanine crosses the placenta and is cleared by the mother's liver, so an affected baby is born with a normal level. Phenylalanine accumulates only once the baby takes milk protein. A spot collected too early can therefore miss PKU, and such babies need a repeat sample. Screening measures phenylalanine itself, not phenylpyruvate.
- A: Screening measures phenylalanine; phenylpyruvate is a later urinary marker.
- C: The enzyme is not transferred to the baby; the mother clears phenylalanine only before birth.
- D: Capillary blood is acceptable at any age; the issue is protein intake.
Question 5 · Medium
Daily urinary creatinine output stays nearly constant for a given person because creatinine:
1. AIs made by the liver at a fixed hourly rate
2. BIs reabsorbed by the renal tubules to keep levels steady
3. CComes mainly from the protein in dietary meat
4. DForms non-enzymatically from muscle creatine phosphate
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Answer: D · Forms non-enzymatically from muscle creatine phosphate
About 1-2% of muscle creatine and creatine phosphate cyclises each day to creatinine, without an enzyme. The amount formed therefore depends on muscle mass, which changes little from day to day. Creatinine is freely filtered and is not reabsorbed, which is why it is used to judge GFR and the completeness of 24-hour collections. A large meat meal can add a little, but diet is not the main source.
- A: The liver makes creatine, not creatinine, and not at a fixed rate.
- B: Creatinine is not reabsorbed; a little is secreted by the tubules.
- C: Dietary meat adds only a small, temporary amount.
Question 6 · Medium
In the Caraway method for serum uric acid, the colour develops because uric acid:
1. AIs oxidised by uricase to give hydrogen peroxide
2. BForms a red complex with alkaline picrate
3. CCondenses with diacetyl monoxime in a hot, strongly acid medium
4. DReduces phosphotungstic acid to tungsten blue in alkali
Answer and explanation in LearnFree account
Question 7 · Hard
A post-operative patient takes 60 g of protein a day. His 24-hour urine urea nitrogen is 12 g. Allowing 4 g/day for other nitrogen losses, and taking protein as 16% nitrogen, his nitrogen balance is:
1. A-2.4 g/day
2. B+6.4 g/day
3. C-6.4 g/day
4. D+44 g/day
Answer and explanation in LearnFree account
Question 8 · Easy
In most transamination reactions, which keto acid accepts the amino group removed from the amino acid?
1. AAlpha-ketoglutarate
2. BPyruvate
3. COxaloacetate
4. DBeta-hydroxybutyrate
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Question 9 · Easy
Creatine is synthesised in the kidney and liver from which three amino acids?
1. AGlycine, arginine and methionine
2. BArginine, ornithine and citrulline
3. CGlutamate, cysteine and glycine
4. DGlycine, serine and cysteine
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Question 10 · Hard
A 3-day-old girl becomes lethargic and breathes fast. Plasma ammonia 520 µmol/L (reference below 100), pH 7.50, pCO2 27 mm Hg, normal anion gap, urine ketones negative. Plasma citrulline is about 40 times the upper reference limit, argininosuccinic acid is not detected, and urine orotic acid is moderately raised. Which enzyme is most likely deficient?
1. AArgininosuccinate lyase
2. BOrnithine transcarbamoylase
3. CCarbamoyl phosphate synthetase I
4. DArgininosuccinate synthetase
Answer and explanation in LearnFree account
Question 11 · Medium
Glutamate dehydrogenase is central to 'transdeamination' because it:
1. AConverts free ammonia into urea in the cytosol
2. BTransfers amino groups from amino acids to pyruvate
3. CJoins glutamate and ammonia to form glutamine
4. DReleases free ammonia from glutamate in liver mitochondria
Answer and explanation in LearnFree account
Question 12 · Medium
One nitrogen atom of urea comes from carbamoyl phosphate. Which compound donates the second nitrogen directly?
1. AOrnithine
2. BGlutamate
3. CGlutamine
4. DAspartate
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Question 13 · Easy
Cystinuria is an inherited defect in the renal and intestinal transport of:
1. APhenylalanine, tyrosine, tryptophan and histidine
2. BCystine, methionine, serine and glycine
3. CLeucine, isoleucine, valine and alanine
4. DCystine, ornithine, lysine and arginine
Answer and explanation in LearnFree account
Question 14 · Hard
A man on high-dose intravenous vitamin C has a serum uric acid of 1.8 mg/dL by the uricase-peroxidase (Trinder) method. The same sample by the direct UV uricase method gives 6.4 mg/dL. What is the most likely cause of the low Trinder result?
1. AAscorbate absorbing light at the reading wavelength
2. BAscorbate destroying hydrogen peroxide before dye forms
3. CAscorbate being oxidised by uricase into urate
4. DAscorbate inhibiting uricase in the reagent
Answer and explanation in LearnFree account
Question 15 · Hard
A baby's Guthrie card is reported normal for phenylalanine. Later it emerges the infant had been on intravenous ampicillin and gentamicin when the spot was taken. At 8 months he has developmental delay and a musty odour. Why was the screening result wrong?
1. AAntibiotics converted phenylalanine to tyrosine in vivo
2. BAntibiotics in the spot inhibited the test bacteria
3. CAntibiotics removed phenylalanine from the infant's urine
4. DAntibiotics made the blood spot dry too slowly
Answer and explanation in LearnFree account
Question 16 · Easy
Aminotransferases such as ALT and AST need which coenzyme to carry the amino group?
1. ATetrahydrofolate
2. BFlavin adenine dinucleotide
3. CThiamine pyrophosphate
4. DPyridoxal phosphate
Answer and explanation in LearnFree account
Question 17 · Medium
Serum creatinine is a poor marker of early kidney disease mainly because:
1. AIt changes widely with each protein-rich meal
2. BIt rises clearly only after about half of the GFR is lost
3. CIt is produced by the liver and falls in renal disease
4. DIt is fully reabsorbed by the tubules in early disease
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Question 18 · Medium
A blood urea nitrogen (BUN) to creatinine ratio below 10:1 is most expected in a patient with:
1. AHigh-dose corticosteroid therapy
2. BSevere dehydration
3. CAdvanced liver cirrhosis
4. DUpper gastrointestinal bleeding
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Question 19 · Medium
Children with untreated phenylketonuria often have fair skin and light hair because:
1. APhenylpyruvate destroys melanin already formed in the skin
2. BPhenylalanine is converted directly into a pale pigment
3. CTetrahydrobiopterin is used up and melanocytes cannot divide
4. DExcess phenylalanine inhibits tyrosinase and tyrosine is scarce
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Question 20 · Hard
A 14-year-old tall, thin boy has a downward-dislocated lens, mild learning difficulty and had a deep vein thrombosis last year. Urine cyanide-nitroprusside test is positive. Plasma methionine is raised and plasma total homocysteine is 190 µmol/L (reference below 15). The most likely diagnosis is:
1. AMarfan syndrome
2. BClassical homocystinuria
3. CCystinuria
4. DVitamin B12 deficiency
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Question 21 · Easy
The rate-limiting enzyme of the urea cycle, found in liver mitochondria, is:
1. AArgininosuccinate synthetase
2. BArginase
3. COrnithine transcarbamoylase
4. DCarbamoyl phosphate synthetase I
Answer and explanation in LearnFree account
Question 22 · Medium
In the Guthrie test for phenylketonuria, beta-2-thienylalanine is added to the agar in order to:
1. AStain the zone of growth around each blood disc
2. BInhibit Bacillus subtilis unless phenylalanine overcomes it
3. CConvert phenylalanine into a coloured derivative
4. DSupply the bacteria with the amino acid they need
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Question 23 · Medium
Creatinine clearance overestimates the true GFR, and the error grows as kidney function worsens, because creatinine is:
1. APartly reabsorbed by the collecting ducts
2. BBroken down in the bladder after collection
3. CBound to albumin and filtered slowly
4. DAlso secreted by the proximal tubules
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Question 24 · Medium
In the kinetic Jaffe method, the absorbance change is read between about 20 and 80 seconds after mixing. The reason is that:
1. ACreatinine does not react with picrate until 20 seconds have passed
2. BThe orange complex fades completely within 80 seconds of forming
3. CFast chromogens like acetoacetate react before, slow ones like protein after
4. DBilirubin is oxidised in the first 20 seconds and stops interfering
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Question 25 · Medium
About half of patients with classical homocystinuria respond to large doses of pyridoxine. This is because:
1. APyridoxine remethylates homocysteine to methionine
2. BPyridoxine increases renal excretion of homocystine
3. CPyridoxine blocks methionine absorption in the gut
4. DCystathionine beta-synthase uses pyridoxal phosphate
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Protein and amino acid metabolism, NPN and inborn errors

According to a widely taught explanation, why is a high ammonia level toxic to the brain? Because ammonia:

Which urea cycle enzyme needs N-acetylglutamate as an essential activator and sets the rate of the whole cycle?

Why is a newborn blood spot for phenylketonuria screening collected only after 24 to 48 hours of milk feeding?

Daily urinary creatinine output stays nearly constant for a given person because creatinine:

In the Caraway method for serum uric acid, the colour develops because uric acid:

A post-operative patient takes 60 g of protein a day. His 24-hour urine urea nitrogen is 12 g. Allowing 4 g/day for other nitrogen losses, and taking protein as 16% nitrogen, his nitrogen balance is:

In most transamination reactions, which keto acid accepts the amino group removed from the amino acid?

Creatine is synthesised in the kidney and liver from which three amino acids?

Glutamate dehydrogenase is central to 'transdeamination' because it:

One nitrogen atom of urea comes from carbamoyl phosphate. Which compound donates the second nitrogen directly?

Cystinuria is an inherited defect in the renal and intestinal transport of:

A man on high-dose intravenous vitamin C has a serum uric acid of 1.8 mg/dL by the uricase-peroxidase (Trinder) method. The same sample by the direct UV uricase method gives 6.4 mg/dL. What is the most likely cause of the low Trinder result?

A baby's Guthrie card is reported normal for phenylalanine. Later it emerges the infant had been on intravenous ampicillin and gentamicin when the spot was taken. At 8 months he has developmental delay and a musty odour. Why was the screening result wrong?

Aminotransferases such as ALT and AST need which coenzyme to carry the amino group?

Serum creatinine is a poor marker of early kidney disease mainly because:

A blood urea nitrogen (BUN) to creatinine ratio below 10:1 is most expected in a patient with:

Children with untreated phenylketonuria often have fair skin and light hair because:

A 14-year-old tall, thin boy has a downward-dislocated lens, mild learning difficulty and had a deep vein thrombosis last year. Urine cyanide-nitroprusside test is positive. Plasma methionine is raised and plasma total homocysteine is 190 µmol/L (reference below 15). The most likely diagnosis is:

The rate-limiting enzyme of the urea cycle, found in liver mitochondria, is:

In the Guthrie test for phenylketonuria, beta-2-thienylalanine is added to the agar in order to:

Creatinine clearance overestimates the true GFR, and the error grows as kidney function worsens, because creatinine is:

In the kinetic Jaffe method, the absorbance change is read between about 20 and 80 seconds after mixing. The reason is that:

About half of patients with classical homocystinuria respond to large doses of pyridoxine. This is because: