Riboflavin functions metabolically as an essential component of the coenzymes FMN and FAD, which act as intermediaries in electron transfers in biological oxidation-reduction reactions. As flavoproteins, they serve as switching sites between obligate two-electron donors and one-electron acceptors, and can transfer one or two electrons with a range of potentials. Riboflavin plays key roles in metabolism through these coenzymes, including carbohydrate, amino acid, lipid, and vitamin metabolism. It is also essential for protecting against oxidative stress and homocysteinemia, and plays roles in vascular disease, congenital defects in fat metabolism, mineral utilization, and other health effects.

1. Metabolic functions of
riboflavin
Domina Petric, MD

2. 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.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
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3. Coenzyme functions
Flavoproteins or flavoenzymes include:
• oxidases, which function
aerobically
• dehydrogenases, which function
anaerobically
Some involve one-electron transfers,
whereas others involve two-electron
transfers.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
3

4. 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).
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
4

5. Coenzyme functions
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
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
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6. 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.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
6

7. 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.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
7

8. 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.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
8

9. 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.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
9

10. Health effects
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
10

11. 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.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
11

12. 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.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
12

13. Homocysteinemia
Increased risks to:
• occlusive vascular disease
• total and cardiovascular disease-
related mortality
• stroke
• dementia
• Alzheimer’s disease
• fracture
• chronic heart failure
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
13

14. 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.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
14

15. 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.
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
15

16. Health effects of riboflavin
Vascular disease
Riboflavin is essential in
the metabolism of
homocysteine.
Mineral utilization
Iron and zinc
Oxidative stress
Protection of erythrocytes
and other cells against
oxidative stress.
Congenital defects in fat
metabolism
Riboflavin plays essential
roles in lipid metabolism.
B2
April 16, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
16

17. Literature
• Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
April 16, 2018 17