19 FumarateSuccinateMalateCitrate<0.110.0 ± 1.0<0.15.5 1.57.1 ± 0.50.5 ± 0.24.2 ± 0.4150 ± 25Fumarase; because the citrate cycle is blocked.Fumarase; because pyruvate is used to make oxaloacetate.Lactate dehydrogenase; because the defect is in this enzyme.Succinate dehydrogenase; because pyruvate is converted to lactate.Malate dehydrogenase; because the citrate cycle is blocked. Defects in the Citrate Cycle are rare but have been described. Based on thelevel of metabolites shown in a patient's blood in the table below, whichhuman metabolic enzyme is most likely defective; and why is the lactate levso high in this patient?CompoundLactateFumarateSuccinateMalateCitratePatient (mmol/L)25.5 ± 1.2<0.110.01.0<0.15.5 ± 1.5Normal control(mmol/L)1.5 ± 0.37.1 ± 0.50.5 ± 0.24.2 ± 0.4150 ± 25Fumarase: because the trato cycle is blocked

Glycolysis consists of 10 enzymatically catalysed reactions that convert one 6-carbon molecule of glucose-6-phosphate into two molecules of 3-carbon pyruvate. Under aerobic conditions, Pyruvate is oxidised to acetyl CoA by the enzyme pyruvate dehydrogenase complex. Acetyl CoA delivers the acetyl group to the TriCarbcoxylic Acid cycle or the citric acid cycle. TCA cycle The TCA cycle used this acetate and water to reduce NAD+ to NADH and FAD+ to FADH2. Acetyl CoA is attached to oxaloacetate to form citrate, citrate is rearranged to isocitrate and oxidized to alpha-ketoglutarate(AKG) by isocitrate dehydrogenase. Isocitrate dehydrogenase reduces 1 NAD+ to NADH and one molecule of CO2 is also released during this reaction. AKG is converted into succinyl CoA by AKG dehydrogenase which also reduces 1 NAD+ to NADH. Succinyl CoA synthetase converts Succinyl CoA to succinate and phosphorylates 1 GDP into GTP. Another enzyme of TCA succinate dehydrogenase oxidises succinate to fumarate while reducing FAD+ to FADH2. Fumarate is converted to malate via a hydration reaction catalysed by fumarase. Lastly, regeneration of oxaloacetate from malate by malate dehydrogenase also reduces 1 NAD+ to NADH For every Acetyl CoA, we get 3NADH and 1 FADH2 and 1 GTP from TCA. NADH/FADH2 enter ETC to regenerate NAD+ and FAD for TCA cycle. Under anaerobic conditions, NADH from glycolysis is used by Lactate dehydrogenase. The enzyme converts pyruvate to lactate to regenerate NAD+ for glycolysis and this conversion generates no ATP. So under anaerobic conditions, ATP is generated from substrate-level phosphorylation.From the test results, we can see that there is enough citrate and succinate but the concentration of fumarate and malate is below normal. A defective/inhibited succinate dehydrogenase would result in low levels of fumarate since this enzyme catalyses the conversion of succinate to fumarate while reducing FAD+ to FADH2. Low levels of malate are likely due to insufficient substrate availability for fumarase, the enzyme that catalyzes the conversion of fumarate to malate. Since succinate dehydrogenase is defective, the TCA cycle is effectively blocked. Another consequence of the TCA cycle being blocked is that there is not sufficient NADH available. Pyruvate instead of entering the TCA cycle as acetyl CoA is converted to lactate to regenerate NAD+. Lactate can be converted back to pyruvate if NADH concentration increases but a blocked TCA cycle leads to insufficient NADH being available. This can lead to the accumulation of lactate. Therefore the correct choice is the fourth option: Succinate dehydrogenase, because pyruvate is converted back to lactate. Defective fumarase would increase the cellular concentration of fumarate. Similarly, defective malate dehydrogenase would result in the accumulation of malate and defective LDH would not catalyse the reversible conversion of pyruvate to lactate; so pyruvate would accumulate instead of lactate. Since test results are opposite of these effects, none of these enzymes is defective. Also, oxaloacetate is converted to pyruvate for gluconeogenesis and the reaction is not reversible. This makes other choices incorrect.