Angular stomatitis and impaired TCA cycle activity

Case details

A postoperative patient on intravenous fluids develops lesions in the mouth (angular stomatitis). Urinalysis indicates an excretion of 15 μg riboflavin/mg creatinine, which is abnormally low. Which of the following TCA cycle enzymes is most likely to be affected?

A. Citrate synthase

B. Isocitrate dehydrogenase

C. Fumarase

D. Malate dehydrogenase

E. Succinate dehydrogenase

Answer- The correct answer is- E- Succinate dehydrogenase

Angular stomatitis and low excretion of riboflavin are indicators of underlying Riboflavin deficiency, hence the activities of only Riboflavin requiring enzymes would be affected .

Riboflavin functions in several different enzyme systems. Two derivatives, riboflavin 5′ phosphate (flavin mononucleotide [FMN]) and riboflavin 5′ adenosine diphosphate (flavin adenine dinucleotide [FAD]), are the coenzymes that unite with specific apoenzyme proteins to form flavoprotein enzymes. Most of the flavin coenzyme systems help to regulate cellular metabolism.

FMN and FAD function as coenzymes for a wide variety of oxidative enzymes and remain bound to the enzymes during the oxidation-reduction reactions. Flavins can act as oxidizing agents because of their ability to accept a pair of hydrogen atoms. Reduction of isoalloxazine ring (FAD, FMN oxidized form) yields the reduced forms of the flavoprotein (FMNH2 and FADH2)

Examples of flavoenzymes are:

  • NADH dehydrogenase (complex-I), that contains FMN and  plays an important role in the electron transport chain
  • L-Amino acid oxidases that cause oxidative deamination of L- amino acids, require FMN
  • PDH complex that catalyzes decarboxylation of pyruvate, and α-Ketoglutarate dehydrogenase complex that catalyzes decarboxylation of α-Keto glutarate require FAD besides other coenzymes.
  • FAD is required as a coenzyme for, monoamine oxidase and glutathione reductase.
  • Fatty acyl CoA dehydrogenase requires FAD in fatty acid oxidation
  • FAD is required for the conversion of Succinate to fumarate by succinate dehydrogenase (complex II) of ETC.
  • Mitochondrial Glycerol-3- p dehydrogenase that catalyzes the conversion of  glycerol-3-P to dihydroxyacetone-P requires FAD
  • FAD is required in the conversion of Xanthine to uric acid by Xanthine oxidase enzyme.
  • FAD is required by Glycine oxidase enzyme.
  • FAD is a cofactor for methyltetrahydrofolate reductase and therefore modulates homocysteine metabolism.

In the given options, Succinate dehydrogenase is the only enzyme that is FAD dependent.

Citrate synthase catalyzes the condensation of acetyl co A and oxaloacetate to form citrate; it does not require riboflavin for its activity.

Isocitrate dehydrogenase and malate dehydrogenase, both of the enzymes require NAD+ as a coenzyme.

Fumarase catalyzes the hydrolysis of fumarate to malate; riboflavin is not required for its action.

TCA cycle

Figure- TCA cycle enzymes and the coenzymes

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