Impaired TCA cycle enzyme activity in angular stomatitis

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?

1. Citrate synthase
2. Isocitrate dehydrogenase
3. Fumarase
4. Malate dehydrogenase
5. Succinate dehydrogenase

Details- E) – Succinate dehydrogenase is the correct answer.

The patient has demonstrated a deficiency in riboflavin (urinary excretion of lesser than 30 μg/mg creatinine is considered clinically deficient). Vitamin B2 deficiency is frequent in chronic alcoholics.  It can also occur in patients with chronic liver diseases and in hospitalized patients who receive total parenteral nutrition (TPN) with inadequate riboflavin supplementation. Riboflavin is essential for healthy skin, nails, hair growth, and general good health, including regulating thyroid activity. Riboflavin supports energy production by aiding in the metabolism of fats, carbohydrates, and proteins. Characteristic symptoms of riboflavin deficiency include lesions of the skin, especially in the corners of the mouth (angular stomatitis), and a red, sore, fissured tongue (Figure 1).

Figure-1- Angular stomatitis

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.

Figure 2- Structure of Riboflavin. It contains D-ribitol and the Isoalloxazine ring( flavin nucleus)

FMN and FAD function as coenzymes for various 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).

Enzymes containing flavin adenine dinucleotide (FAD) or flavin-mononucleotide (FMN) as prosthetic groups are flavoenzymes.

Succinate dehydrogenase is the only FAD-dependent enzyme in the TCA cycle. Succinate dehydrogenase catalyzes the conversion of succinate to fumarate. The reaction catalyzed can be represented as follows:

Figure-3- Reaction catalyzed by succinate dehydrogenase

As regards other options

Citrate synthase catalyzes the condensation of acetyl co A and oxaloacetate to form Citrate (figure-4); it does not require FMN or FAD as a coenzyme.

Figure 4- TCA cycle enzymes and the steps of the TCA cycle. (IDH is isocitrate dehydrogenase)

 Isocitrate and malate dehydrogenase are NAD ⁺ enzymes.

 Fumarase catalyzes the conversion of Fumarate to malate and does not require riboflavin as a coenzyme. Thus out of all the given options, Succinate dehydrogenase is the only TCA cycle enzyme, the activity of which can be affected in riboflavin deficiency.

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