Vitamin cofactor functions

Vitamin E (tocopherol) is the most important antioxidant in the body, acting in the lipid phase of membranes and protecting against the effects of free radicals. Vitamin K functions as cofactor to a carboxylase that acts on glutamate residues of clotting factor precursor proteins to enable them to chelate calcium. 

The water-soluble vitamins generally function as cofactors for metabolism enzymes such as those involved in the production of energy from carbohydrates and fats. Their members consist of vitamin C and vitamin B complex which include thiamine, riboflavin (vitamin B2), nicotinic acid, pyridoxine, pantothenic acid, folic acid, cobalamin (vitamin B12), inositol, and biotin. A number of recent publications have demonstrated that vitamin carriers can transport various types of water-soluble vitamins, but the carrier-mediated systems seem negligible for the membrane transport of fat-soluble vitamins such as vitamin A, D, E, and K. 

Coenzyme/ Cofactor Type of Binding Derived from Vitamin Physiologic Function... 

In normal individuals phytonadione and the menaquinones have no activity while in vitamin K deficiency the vitamin promotes the hepatic biosynthesis of factor II (prothrombin), factor VII, factor IX and factor X. Vitamin K functions as an essential cofactor for the enzymatic activation of precursors of these vitamin K dependent clotting factors. The quinone structure of the active form of vitamin K, i.e. reduced vitamin K or hydroquinone. 

Vitamin B12 is a biologically active corrinoid, a group of cobalt-containing compounds with macrocyclic pyrrol rings. Vitamin B12 functions as a cofactor for two enzymes, methionine synthase and L-methylmalonyl coenzyme A (CoA) mutase. Methionine synthase requires methylcobalamin for the methyl transfer from methyltetrahydrofolate to homocysteine to form methionine tetrahy-drofolate. L-methylmalonyl-CoA mutase requires adenosylcobalamin to convert L-methylmalonyl-CoA to succinyl-CoA in an isomerization reaction. An inadequate supply of vitamin B12 results in neuropathy, megaloblastic anemia, and gastrointestinal symptoms (Baik and Russell, 1999). 

Vitamins, cofactors, and metals have the potential to broaden the scope of antibody catalysis considerably. In addition to hydrolytic and redox reactions, they facilitate many complex functional group interconversions in natural enzymes.131 Pyridoxal, for example, plays a central role in amino acid metabolism. Among the reactions it makes possible are transaminations, decarboxylations, racemizations, and (3,y-eliminations. It is also essential for ethylene biosynthesis. Not surprisingly, then, several groups have sought to incorporate pyridoxal derivatives into antibody combining sites. 

The coumarin anticoagulants, which include warfarin [WAR far in] and dicumarol [dye KOO ma role] (formerly bishydroxycoumarin) owe their action to their ability to antagonize the cofactor functions of vitamin K. Initially used as a rodenticide, warfarin is now widely employed clinically as an oral anticoagulant. Conflicting opinions exist concerning the usefulness of these agents in clinical situations such as myocardial infarction and hip arthroplasty. The potential... 

The unusual nature of the red cobalt complex (I) induced considerable activity in the field of coordination chemistry vitamin B12 derivatives were found to represent unique examples of kinetically labile Co complexes, the analysis of whose model type coordination chemistry itself proved to be of particular value.Interestingly, for the transition metal cobalt, no other cofactor function has been clearly established, except for that in the B -derivatives. ... 

Cofactors assist enzymes in catalyzing a variety of reactions that cannot be catalyzed solely by their amino acid side chains. Cofactors can be metal ions or organic molecules. An enzyme with a tightly bound metal ion is called a metalloenzyme. Cofactors that are organic molecules are called coenzymes and these are derived from vitamins. A vitamin is a substance the body cannot synthesize that is needed in small amounts for normal body function. All the water-soluble vitamins except vitamin C function as coenzymes. Vitamin K is the only water-insoluble vitamin currently recognized to function as a coenzyme. 

Protein S. Protein S is a single-chain molecule of approximately 78,000 daltons that contains 10 y-carboxy glutamic acid residues in the NH -terminal portion of the molecule. Protein S is a regulatory vitamin K-dependent protein. In plasma 40% of this protein circulates free and 60% circulates bound to C4b binding protein. Free Protein S functions as a nonenzymatic cofactor that promotes the binding of Protein C to membrane surfaces (22—25). 

Many enzymes carry out their catalytic function relying solely on their protein structure. Many others require nonprotein components, called cofactors (Table 14.2). Cofactors may be metal ions or organic molecules referred to as coenzymes. Cofactors, because they are structurally less complex than proteins, tend to be stable to heat (incubation in a boiling water bath). Typically, proteins are denatured under such conditions. Many coenzymes are vitamins or contain vitamins as part of their structure. Usually coenzymes are actively involved in the catalytic reaction of the enzyme, often serving as intermediate carriers of functional groups in the conversion of substrates to products. In most cases, a coenzyme is firmly associated with its enzyme, perhaps even by covalent bonds, and it is difficult to... 

Therapeutic Function Enzyme Cofactor vitamin source Chemicel Name Sae Structural Formula... 

Peptidyl hydroxyprohne and hydroxylysine are formed by hydroxylation of peptidyl proline or lysine in reactions catalyzed by mixed-function oxidases that require vitamin C as cofactor. The nutritional disease scurvy reflects impaired hydroxylation due to a deficiency of vitamin C. 

The water-soluble vitamins comprise the B complex and vitamin C and function as enzyme cofactors. Fofic acid acts as a carrier of one-carbon units. Deficiency of a single vitamin of the B complex is rare, since poor diets are most often associated with multiple deficiency states. Nevertheless, specific syndromes are characteristic of deficiencies of individual vitamins, eg, beriberi (thiamin) cheilosis, glossitis, seborrhea (riboflavin) pellagra (niacin) peripheral neuritis (pyridoxine) megaloblastic anemia, methyhnalonic aciduria, and pernicious anemia (vitamin Bjj) and megaloblastic anemia (folic acid). Vitamin C deficiency leads to scurvy. 

Besides other functions, vitamin Bj2 and fohc acid take part in providing one-carbon residues for DNA synthesis, deficiency resulting in megaloblastic anemia. Vitamin C is a water-soluble antioxidant that maintains vitamin E and many metal cofactors in the reduced state. 

The structures of the vitamins and cofactors shown in this table are not complete structures. Only the functional parts of the molecules are shown. 

The way in which thiamine participated in the oxidation of pyruvate became clearer when Lohmann and Schuster (1937) showed vitamin Bj to be present intracellularly as thiamine pyrophosphate. In yeast, decarboxylation of pyruvate yielded ethanal which was reduced by alcohol dehydrogenase to give ethanol. A cofactor was needed for this decarboxylation, co-carboxylase. Like the cofactor needed in animal cells for the decarboxylation of pyruvate, cocarboxylase was found to be identical to thiamine pyrophosphate. Vitamin Bj thus became the first vitamin whose intracellular function as a coenzyme had been established in vitro. Another aphorism therefore arose about vitamins—B vitamins are (parts of) coenzymes—an idea that was to be completely confirmed. 

Vitamin B12 (cobalamin 22) and fohc acid (23) are among the essential nutrients and are involved primarily as cofactors in metabolic functions as... 

Special tasks. Some lipids have adopted special roles in the body. Steroids, eicosanoids, and some metabolites of phospholipids have signaling functions. They serve as hormones, mediators, and second messengers (see p.370). Other lipids form anchors to attach proteins to membranes (see p.214). The lipids also produce cofactors for enzymatic reactions—e.g., vitamin K (see p.52) and ubiquinone (see p.l04). The carotenoid retinal, a light-sensitive lipid, is of central importance in the process of vision (see p.358). 

Niacin is also known as vitamin PP or vitamin Bj. The term niacin describes two related compounds, nicotinic acid and nicotinamide (Figure 19.18), both with biological activity. Niacin is formed from the metabolism of tryptophan, and therefore it is not strictly a vitamin. It is a precursor of two cofactors nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which are essential for the functioning of a wide range of enzymes involved in redox reactions. 

Physiologically, distinction from folate deficiency is often clinically and haematologically difficult because vitamin B12, also known as cobalamin, functions as an essential cofactor for folate metabolism in the evenmal synthesis of deoxyribonucleic acid. 

Mechanism of Action A fat-soluble vitamin that may act as a cofactor in biochemical reactions. Therapeutic Effect Is essential for normal function of retina, visual adaptation to darkness, bone growth, and testicular and ovarian function preserves integrity of epithelial cells. 

Like folate and vitamin C, vitamin B6 (pyroxidine) is water soluble and like folate has several vitamers. Vitamin B6 may be involved in more bodily functions than any other nutrient (Tambasco-Studart et al., 2005), is a cofactor for many enzymes, especially those involved in protein metabolism, and is also a cofactor for folate metabolism. Vitamin B6 has anticancer activity (Theodoratou et al., 2008), is a strong antioxidant (Denslow et al., 2005), is involved in hemoglobin biosynthesis, lipid and glucose metabolism and immune and nervous system function. Possible consequences of deficiency include anemia, impaired immune function, depression, confusion, and dermatitis (Spinneker et al., 2007). Vitamin B6 deficiency is generally not a problem in the developed world, but there could be as yet poorly defined consequences of suboptimal intake particularly for the elderly. 

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