VITAMIN B2

VITAMIN B2

A. History. Riboflavin or vitamin B2 was first isolated in 1879 from milk whey which is an essential dietary factor
for rats. Since it was first isolated from milk, vitamin B2 is also known as lactoflavin. Originally, it was also known
as ovoflavin (from eggs) and hepatoflavin (from liver). Its synthesis was done by Richard Kuhn and Paul
Karrer. It is popularly called as the “yellow enzyme” because of its colour.
B. Occurrence. In nature, it occurs almost exclusively as a constituent of one of the two flavin coenzymes, namely, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). Milk, cheese, eggs, liver, kidney, heart and brewer’s yeast are excellent sources of this vitamin. Cow’s milk contains about 5 times as much riboflavin as human milk. Leafy vegetables are good sources. They are usually richer in riboflavin than they are in thiamine. Fruits and most root vegetables contain moderate quantities. Whole grains, cereals and milled flour contain low riboflavin content. The riboflavin contents in cereals, however, increase strikingly during germination. The ordinary cooking processes do not affect the riboflavin content of the food. Roasted or boiled meat retains about 75% of the vitamin. It is only very rarely that vitamin B2 is present in free or uncombined state as in retina and spleen. Fermentation residues from alcohol manufacture probably offer the richest large supplies.
C. Structure. Riboflavin (C17H20N4O6) belongs to a class of water-soluble pigments called lyochromes. A molecule of thiamine consists of a sugar alcohol, D-ribitol, attached to a chromogenic dimethyl isoalloxazine ring atposition number9.
D. Properties. Riboflavin is a bright orange-yellow crystalline powder. It is soluble in water and ethanol but insoluble in ether and chloroform. It is stable to heat and acids but is easily decomposed by alkalies and exposure to light. The aqueous solution exhibits yellow-green fluorescence. It stands ordinary cooking and canning. On exposure to light, the ribityl residue splits off, forming a compound lumiflavin in alkaline solution and lumichrome in acidic or neutral
solution.
E. Metabolism. Flavokinase Riboflavin is synthesized by all green plants, most bacteria, yeasts and moulds. Ashbya gossypii, an yeast, produces it in such large amounts that riboflavin crystals are formed in the culture medium. Animals have, so far, not been shown to synthesize riboflavin. In man, the ingested riboflavin is largely passed out as such or as its coenzyme, the FMN. Experiments with plant tissues have suggested that riboflavin and flavoproteins may play a significant role in phototropic curvature of various plant organs (Galston, 1950). Riboflavin is essential for growth and tissue respiration; it may have a role in light adaptation and is required for conversion of pyridoxine to pyridoxal phosphate. When riboflavin is phosphorylated in the presence of an enzyme, flavokinase, it gets converted to FMN which is essential in the biosynthesis of fats.

Riboflavin + ATP l FMN + ADP

FMN may undergo a further reaction with ATP, in the presence of an enzyme found in yeast and animal tissues, to produce FAD. It is a chief constituent of electron transport system (ETS). A decrease in the amount of FAD, therefore, would severely hamper the efficiency of ETS.

FMN + AMP l FAD + PP

The coenzymes undergo reversible oxidation-reduction in the presence of their enzymes and a suitable substrate. The flavoenzymes play a key role in cell metabolism. They function in accepting hydrogen atoms from reduced pyridine nucleotides. They have been shown to participate in the enzymic oxidation of glucose, fatty acids, amino acids and purines.
F. Deficiency. Riboflavin deficiency is usually caused by inadequate intake. Faulty absorption may contribute in patients with biliary atresia or hepatitis or in those receiving probenecid, phenothiazine or oral contraceptives. Phototherapy destroys riboflavin content. It is interesting to note that riboflavin deficiency without deficiency of other member of the B complex is rare. Persons deficient in vitamin B2 show chelosis (fissuring at the corners of the mouth and lips), glossitis (inflammation of the tongue), keratitis, conjunctivitis photophobia, lacrimation, corneal vascularization (bloodshot eyes) and seborrheic dermatitis. But these symptoms are not specific to ariboflavinosis since similar symptoms may also develop in the absence of nicotinic acid and iron. Cheilosis (= perle′che) begins with pallor at the angles of the mouth, following by thinning and maceration of the epithelium. Superficial fissures often covered by yellow crusts develop in the angles of the mouth and extend radially into the skin for distances upto 2 cm. In glossitis, the tongue is smooth, and loss of papillary structure occurs. A normocytic and normochronic anemia with bone marrow hyperplasia is common. However, patients suffering from pellagra and beriberi are usually also deficient in riboflavin content.
G. Human requirements. The minimum daily requirement of riboflavin varies from 0.6 to 1.7 mg for children and adults. During pregnancy and lactation, the women require up to 2.0 mg
daily.
H. Treatment : Ariboflavinosis may be prevented by a diet that contains adequate amounts of milk, eggs, leafy vegetables, and lean meats. Treatment consists in oral administration of 3-10 mg of riboflavin daily. If no response occurs within a few days, intramuscular injections of 2 mg of riboflavin in saline solution may be administered 3 times in a day.

VITAMIN B3

A. History: This was first isolated by Roger J. Williams in 1938 from yeast and liver concentrates. On account of its wide distribution, he named it as pantothenic acid (pantosG = everywhere). The coenzyme form of this vitamin (coenzyme A or CoA-SH) was isolated and its structure determined by Fritz A. Lipmann. The chemical synthesis of this coenzyme was, however, described by Khorana in 1959. This vitamin is sometimes called as filtrate factor or the yeast factor.
B. Occurrence: Although widespread in nature, yeast, liver and eggs are the richest sources of it. The vegetables (potatoes, sweet potatoes, cabbage, cauliflower, broccoli) and fruits (tomatoes, peanuts) and also the skimmed milk, wheat bran, whole milk and canned salmon are some of the less important sources. In most animal tissues and microorganisms, it occurs as its coenzyme.
C. Structure: Pantothenic acid (C9H17NO5) is an amide of pantoic acid (α, γ-dihydroxy-β, β-dimethyl butyric acid) and β-alanine D. Properties. Pantothenic acid is a pale yellow viscous oil, soluble in water and ethyl acetate but insoluble in chloroform. It is stable to oxidizing and reducing agents but is destroyed by heating in an acidic and alkaline medium (i.e., it is heat-labile).
E. Metabolism: Pantothenic acid can be synthesized by green plants and various microorganisms (Neurospora, Escherichia coli, Bacteria linens) but not by mammals. Hence, this must be present in the diet to serve as a starting point for coenzyme A (CoA). Coenzyme A is richly found in the liver and in poor quantities in the adrenals. There may be as much as 400 mg of CoA per kilo of liver. It functions in acetylation reactions. In order to be effective, CoA must be present in the form of acetyl-CoA. It may arise in many ways but the most common way of its production is that CoA, in the presence of ATP, acetate and a suitable enzyme, is converted into acetyl CoA. The overall reaction may be shown in 3 steps :

• ATP + Enzyme ���� ������������ Adenylic acid-Enzyme + Pyrophosphate
• Adenylic acid-Enzyme + CoA ���� ������������ CoA-Enzyme + Adenylic acid
• CoA-Enzyme + Acetate ���� ������������ Acetyl-CoA + Enzyme
  

The acetyl groups may be transferred to an acetyl acceptor in the presence of a suitable acceptor. This may occur in two ways : either the acetyl group is attached to the accepting groupat the carbonyl end (head reaction) or at the methyl end (tail reaction).The only known metabolic fate of vitamin B3 is its participation in the formation of the biologically important coenzyme A. It functions as a thioester of carboxylic acids.
F. Deficiency: A deficiency of pantothenic acid leads to depigmentation of the hair in rats, pigs and dogs and to depigmentation of feathers in chicks. Atrophy of the adrenal cortex with necrosis and hemorrhage may also occur in animals including rat. Corneal changes consisting of vascularization, thickening and opacity may be seen. In human beings, no definite deficiency syndrome has been ascribed to pantothenic acid, probably because of the ubiquitous nature of this vitamin and because of the fact that a little amount of this vitamin can perhaps be synthesized in the body. Its correlation with achromotrichia (premature greying of the hair) has been described in the case of man, sometimes. But it seems too much to hope that grey hair can be averted by attention to diet ; rather it appears we must expect to go grey in spite of this vitamin.
G. Human requirements: The dietary allowance dose has not been officially worked out. Yet, 5—10 mg per day of vitamin B3 has been suggested.