Metabolic functions of riboflavin Domina Petric, MD

Coenzyme functions Riboflavin functions metabolically as the essential component of the coenzymes FMN and FAD, which act as intermediaries in transfers of electrons in biological oxidation-reduction reactions. November 22, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Coenzyme functions oxidases, which function aerobically Flavoproteins or flavoenzymes include: oxidases, which function aerobically dehydrogenases, which function anaerobically Some involve one-electron transfers, whereas others involve two-electron transfers. November 22, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Coenzyme functions Flavoproteins serve as switching sites between obligate two-electron donors (NADH, succinate) and obligate one-electron acceptors (iron–sulfur proteins, heme proteins). Flavoproteins serve this function by undergoing reduction through two single-electron transfer steps involving a riboflavinyl radical or semiquinone intermediate (with the unpaired electron localized at N-5). November 22, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Coenzyme functions two-electron reduction of O2 to H2O Because the radical intermediate can react with molecular oxygen, flavoproteins can also serve as cofactors in: two-electron reduction of O2 to H2O four-electron activation and cleavage of O2 in monooxygenase reactions November 22, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Coenzyme functions The flavoproteins show great versatility in accepting and transferring one or two electrons with a range of potentials. This feature can be attributed to the variation in the angle between the two planes of the isoalloxazine ring system (intersecting at N-5 and N-10), which is modified by specific protein binding. November 22, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Coenzyme functions The flavin-containing dehydrogenases or reductases (their reduced forms) react slowly with molecular oxygen, in contrast to the fast reactions of the flavin-containing oxidases and monooxygenases. November 22, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Many flavoproteins contain a metal (iron, molybdenum, zinc). Coenzyme functions Many flavoproteins contain a metal (iron, molybdenum, zinc). The combination of flavin and metal ion is often involved in the adjustments of these enzymes in transfers between single- and double-electron donors. In some flavoproteins, the means for multiple-electron transfers is provided by the presence of multiple flavins as well as metals. November 22, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Metabolic roles The flavoproteins are essential for the metabolism of carbohydrates, amino acids and lipids. Some are also essential for the activation of the vitamins pyridoxine and folate to their respective coenzyme forms. November 22, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Health effects November 22, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Oxidative stress Flavoenzymes participate in protection of erythrocytes and other cells against oxidative stress. This includes the support of intracellular levels of reduced glutathione via glutathione reductase and the direct reduction of oxidized forms of hemoproteins by methemoglobin reductases. November 22, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Vascular disease Riboflavin is essential in the metabolism of homocysteine. FAD is a required coenzyme of methyltetrahydrofolate reductase, the enzyme responsible for converting N-5,10-methylenetetrahydrofolate to N-5-methyltetrahydrofolate. Impairments in that conversion are manifested as homocysteinemia. November 22, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Homocysteinemia occlusive vascular disease Increased risks to: occlusive vascular disease total and cardiovascular disease-related mortality stroke dementia Alzheimer’s disease fracture chronic heart failure November 22, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Congenital defects in fat metabolism As essential coenzymes for acyl-CoA dehydrogenase and NADH dehydrogenase, riboflavin plays essential roles in lipid metabolism. Riboflavin therapy has been found useful in treating cases of deficient expression of these enzymes that otherwise involve recurrent hypoglycemia and lipid storage myopathy. FAD-dependent pathways are involved in the oxidative folding, due to the formation of disulfide bonds, of secretory proteins in the endoplasmic reticulum such as apolipoprotein B-100. November 22, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Mineral utilization Riboflavin has the capacity to form complexes with divalent cations such as iron (Fe2+) and zinc (Zn2+). Riboflavin is probably a determinant of the bioavailability of such minerals. November 22, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Health effects of riboflavin Oxidative stress Protection of erythrocytes and other cells against oxidative stress. Mineral utilization B2 Vascular disease Iron and zinc Riboflavin is essential in the metabolism of homocysteine. Congenital defects in fat metabolism Riboflavin plays essential roles in lipid metabolism. November 22, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Literature Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. November 22, 2018