The two biologically active forms of B2 are flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), formed by the transfer of an adenosine monophosphate moiety from ATP to FMN (Fig. 28.15). FMN and FAD are each capable of reversibly accepting two hydrogen atoms, forming FMNH2 or FADH2, respectively. FMN and FAD are bound tightly, sometimes covalently, to flavoenzymes (for example, NADH dehydrogenase [FMN] and succinate dehydrogenase [FAD]) that catalyze the oxidation or reduction of a substrate. Riboflavin deficiency is not associated with a major human disease, although it frequently accompanies other vitamin deficiencies. Deficiency symptoms include dermatitis, cheilosis (fissuring at the corners of the mouth), and glossitis (the tongue appearing smooth and dark). [Note: Because riboflavin is light sensitive, phototherapy for hyperbilirubinemia (see p. 285) may require supplementation with the vitamin.]
IX. BIOTIN (VITAMIN B7)
Biotin is a coenzyme in carboxylation reactions, in which it serves as a carrier of activated carbon dioxide (CO2) (see Fig. 10.3, p. 119, for the mechanism of biotin-dependent carboxylations). Biotin is covalently bound to the ε-amino group of lysine residues in biotin-dependent enzymes (Fig. 28.16). Biotin deficiency does not occur naturally because the vitamin is widely distributed in food. Also, a large percentage of the biotin requirement in humans is supplied by intestinal bacteria. However, the addition of raw egg white to the diet as a source of protein can induce symptoms of biotin deficiency, namely, dermatitis, hair loss, loss of appetite, and nausea. Raw egg white contains the glycoprotein avidin, which tightly binds biotin and prevents its absorption from the intestine. With a normal diet, however, it has been estimated that 20 eggs/day would be required to induce a deficiency syndrome. [Note: Inclusion of raw eggs in the diet is not recommended because of the possibility of salmonellosis caused by infection with Salmonella enterica.]
Multiple carboxylase deficiency results from decreased ability to add biotin to carboxylases during their synthesis or to remove it during their degradation. Treatment is biotin supplementation.
X. PANTOTHENIC ACID (VITAMIN B5)
Pantothenic acid is a component of CoA, which functions in the transfer of acyl groups (Fig. 28.17). CoA contains a thiol group that carries acyl compounds as activated thiol esters. Examples of such structures are succinyl CoA, fatty acyl CoA, and acetyl CoA. Pantothenic acid is also a component of the acyl carrier protein domain of fatty acid synthase (see p. 184). Eggs, liver, and yeast are the most important sources of pantothenic acid, although the vitamin is widely distributed. Pantothenic acid deficiency is not well characterized in humans, and no RDA has been established.
XI. VITAMIN A
Vitamin A is a fat-soluble vitamin that comes primarily from animal sources as retinol (preformed vitamin A), a retinoid. The retinoids, a family of structurally related molecules, are essential for vision, reproduction, growth, and maintenance of epithelial tissues. They also play a role in immune function. Retinoic acid, derived from oxidation of retinol, mediates most of the actions of the retinoids, except for vision, which depends on retinal, the aldehyde derivative of retinol.
A. Structure
The retinoids include the natural forms of vitamin A, retinol and its metabolites (Fig. 28.18), and synthetic forms (drugs).
1.