A physician-validated, board-style question from the Active Transport QBank. Try it, then check the reasoning for every option.
A 4-month-old boy is brought to the physician because of a seizure. He was delivered at term after an uncomplicated pregnancy. He is currently at the 10th percentile for height, 5th percentile for weight, and 15th percentile for head circumference. Examination shows muscle hypotonia. His serum lactic acid and alanine are elevated. A functional assay of pyruvate dehydrogenase complex in serum leukocytes shows decreased enzyme activity. Supplementation with which of the following substances should be avoided in this patient?
-
A
Arachidonic acidIncorrect. Arachidonic acid is a fatty acid that yields acetyl-CoA via β-oxidation, bypassing the PDH block — beneficial, not avoided.
-
B
ValineCorrect. valine is purely glucogenic; it would feed back into the pyruvate pool and worsen lactic acidosis in PDH deficiency, so it should be avoided.
-
C
LysineIncorrect. Lysine is purely ketogenic (yields acetyl-CoA directly without passing through pyruvate), making it BENEFICIAL in PDH deficiency.
-
D
ThiamineIncorrect. Thiamine is a cofactor for PDH (TPP); supplementation can partially restore residual activity and is therapeutic, not avoided.
-
E
LeucineIncorrect. Leucine is purely ketogenic and yields acetyl-CoA directly, bypassing the PDH block; like lysine, it would be beneficial rather than avoided in PDH deficiency.
↑ Tap an answer to reveal the reasoning
Answer: B. This infant with developmental delay, lactic acidosis (elevated lactate), elevated alanine, and decreased pyruvate dehydrogenase (PDH) complex activity has PYRUVATE DEHYDROGENASE COMPLEX DEFICIENCY. PDH converts pyruvate → acetyl-CoA, linking glycolysis to the TCA cycle. When PDH fails:
1. Pyruvate accumulates and is shunted to lactate (lactic acidosis) and alanine (transamination).
2. Acetyl-CoA production from carbohydrate sources fails.
3. The brain — heavily dependent on glucose/acetyl-CoA — is severely affected (developmental delay, hypotonia, seizures, microcephaly).
Treatment: increase intake of KETOGENIC substrates (lysine and leucine are PURELY ketogenic — degrade to acetyl-CoA bypassing PDH) and a HIGH-FAT, low-carb diet. Thiamine supplementation helps because thiamine pyrophosphate is a PDH cofactor (E1 subunit).
WHAT TO AVOID: GLUCOGENIC amino acids that funnel back to pyruvate and worsen lactic acidosis. VALINE is purely GLUCOGENIC (along with methionine, threonine, histidine) and would worsen the metabolic block. So valine supplementation should be avoided.
Mnemonic: "PVT TIM HALL" (Purely ketogenic = Leucine, Lysine. Both = Isoleucine, Phenylalanine, Threonine, Tryptophan. Rest are glucogenic). Among the options, VALINE is purely glucogenic.
Arachidonic acid is a fatty acid (provides acetyl-CoA via β-oxidation — beneficial). Lysine is ketogenic (beneficial). Thiamine is the PDH cofactor (beneficial).
**Why each option:**
**A.** Arachidonic acid is a fatty acid that yields acetyl-CoA via β-oxidation, bypassing the PDH block — beneficial, not avoided.
**B.** Correct — valine is purely glucogenic; it would feed back into the pyruvate pool and worsen lactic acidosis in PDH deficiency, so it should be avoided.
**C.** Lysine is purely ketogenic (yields acetyl-CoA directly without passing through pyruvate), making it BENEFICIAL in PDH deficiency.
**D.** Thiamine is a cofactor for PDH (TPP); supplementation can partially restore residual activity and is therapeutic, not avoided.