Vitamin B 2 Riboflavin Structure Riboflavin consists of

Vitamin B 2 Riboflavin

Structure • Riboflavin consists of flavin (isoalloxazine ring), to which is attached a ribitol (sugar alcohol) side chain. • The structures of riboflavin determined in 1933. • Riboflavin was isolated and then later synthesized. • The name riboflavin signifies the presence of a ribose likeside chain (ribo) and its yellow color (flavus means “yellow” in Latin).

Structure • Riboflavin consists of three rings structure (isoalloxazine) linked to ribityl moiety. (sugar alcohol) side chain. • Kuhn and coworkers are determining its structure along with Szent-Gyorgyi and Wagner-Jaunergy in 1933.

Structure of riboflavin and its coenzyme • Riboflavin • Flavin mononucleotide (FMN) (coenzyme) • Flavin adenine dinucleotide (FAD) (coenzyme).

Sources • Riboflavin is found in a wide variety of foods, especially animal origin. • Milk and milk products such as cheeses are thought to contribute most dietary riboflavin. • Eggs, meat, and legumes also provide riboflavin in significant quantities. • Green vegetables like spinach provide fairly good riboflavin content. • Fruits and cereal grains are minor contributors of dietary riboflavin. • The form of riboflavin in food varies. Free or proteinbound riboflavin is found in milk, eggs, and enriched breads and cereals. • In most other foods the vitamin occurs as one or the other of its coenzyme derivatives, FMN or FAD, although phosphorus-bound riboflavin is also found in some foods.

Sources

Stability • Stabile to heat, oxidation & acid. • Unstable to light in both acidic and basic medium. • Addition of baking soda to beans destroy much of their riboflavin content. • Milk in proper containers is protected against losses • Dried sun fruits lose some of their riboflavin.

DIGESTION, ABSORPTION, TRANSPORT, AND STORAGE • In stomach • Riboflavin attached to proteins may be freed by the action of hydrochloric acid HCL secreted within the stomach and by gastric and intestinal enzymatic hydrolysis of the protein. • Within intestinal lumen, • FAD converted to FMN and FMN in turn is converted to free riboflavin by FMN phosphatase. FAD pyrophosphatase FAD FMN phosphatase Riboflavin

ABSORPTION • Not all bound riboflavin is hydrolyzed and absorbed. • A small amount (~7%) of FAD is covalently bound to either of two amino acids, histidine or cysteine. • For example, following consumption of foods containing succinate dehydrogenase or monoamine oxidase, these proteins are degraded; however, the riboflavin remains bound, typically to histidine or cysteine residues, and cannot function in the body. • The complex is excreted unchanged in the urine.

ABSORPTION • Generally, animal sources of riboflavin are thought to be better absorbed than plant sources. • Divalent metals such as copper, zinc, iron, and manganese have been shown to chelate (bind to) riboflavin and FMN and to inhibit riboflavin absorption. • Ingestion of alcohol also impairs riboflavin digestion and absorption.

ABSORPTION • In small intestine: • Free riboflavin is absorbed by a saturable, energydependent carrier mechanism. • It also occurs by sodium-independent carriers. • When large amounts of the vitamin are ingested, riboflavin may be absorbed by diffusion. • Absorption rate is proportional to dose. • About 95% of riboflavin intake from foods is absorbed, up to a maximum of about 25 mg. • Peak concentrations of the vitamin in the plasma correlate with intakes of 15 to 20 mg.

ABSORPTION • Within intestinal cells: • Riboflavin is phosphorylated to form FMN, a reaction catalyzed by flavokinase and requiring ATP.

ABSORPTION • At the serosal surface • Most of the FMN is dephosphorylated by a nonspecific alkaline phosphatase to riboflavin, which enters portal blood for transport to the liver. • In liver: • The vitamin is converted to FMN and to its other coenzyme derivative FAD. • FAD is the predominant flavoenzyme in tissues.

TRANSPORTED • Most flavins in systemic plasma are found as riboflavin rather than as one of its coenzyme forms. • All vitamin forms are transported in the plasma by proteins, including albumin, fibrinogen, and globulins (principally immunoglobulins). • Albumin appears to be the primary transport protein. • Immunoglobulins use riboflavin to activate the antibody-catalyzed water H 2 O 2 • Hydrogen peroxide assists in the destruction of foreign antigens.

TRANSPORTED • The free riboflavin is the form that traverses most cell membranes by a carrier-mediated process. • Riboflavin carriers in some tissues such as the liver regulated by calcium/calmodulin. • Diffusion, may also contribute when riboflavin concentrations are high. • Riboflavin is stored in the liver, kidney, and heart in form of FAD (70 -90%) or FMN) or Riboflavin. .

TRANSPORTED • Free riboflavin is transported into and out of cells, within cells. • Riboflavin is typically converted to its coenzyme forms by flavokinase and FAD synthetase, both of which are widely distributed in tissues, especially the liver, small intestine, kidneys, and heart. • Synthesis of FMN and FAD regulated by hormones: aldosterone, and the thyroid hormones. • They accelerate the conversion by increasing the activity of flavokinase product inhibition in the case of FAD synthesis. • After that, vitamin coenzymes become bound to apoenzymes. • FMN and FAD function as prosthetic groups for enzymes involved in oxidation reduction reactions called flavoproteins.

FUNCTIONS AND MECHANISMS OF ACTION • FMN and FAD • Are coenzymes for a wide variety of oxidative enzyme systems and remain bound to the enzymes during the oxidation-reduction reactions. • Flavins • Act as oxidizing agents , which has an ability to accept a pair of hydrogen atoms. • The isoalloxazine ring is reduced and yielding reduced forms of the flavoprotein, which can be found in FMNH 2 and FADH 2.

METABOLISM AND EXCRETION • Riboflavin and its metabolites are excreted primarily in the urine, with only small amounts lost in the feces. • Fecal riboflavin metabolites may also arise from the catabolism of riboflavin by intestinal flora. • Most riboflavin (~60%– 70%) is excreted intact in the urine in amounts >120 μg/day. • Urinary excretion of riboflavin may be noticeable after two hours of ingestion of the vitamin.

RDA • The latest (2005) recommendations for riboflavin • For adults 1. 2 mg (for person with <2. 000 kcal) • For adult men 1. 3 mg/d • For adult women 1. 1 mg/d • For pregnancy 1. 4 mg/d • For lactation 1. 6 mg/d

DEFICIENCY: ARIBOFLAVINOSIS • Rarely occurs in isolation but most often is accompanied by other nutrient deficits. • Clinical symptoms of deficiency after almost 4 months of inadequate intake include lesions on the outside of the lips (cheilosis) and corners of the mouth (angular stomatitis), inflammation of the tongue (glossitis), redness or bloody (hyperemia) and swollen (edema) mouth/oral cavity, an inflammatory skin condition seborrheic dermatitis, anemia and eye disorders. • Severe deficiency of riboflavin may diminish the synthesis of the coenzyme form of vitamin B 6 and the synthesis of niacin (NAD) from tryptophan.

DEFICIENCY: ARIBOFLAVINOSIS

TOXICITY • Toxicity associated with large oral doses of riboflavin has not been reported, and no tolerable upper intake level for riboflavin has been established. • Trials have shown use of large amounts (400 mg) of the vitamin to be effective in treating migraine headaches without side effects.