Vitamin coenzyme forms

Vitamin Coenzyme Form Reaction or Process Promoted... 

Table 23-6. Essential Vitamins, Coenzyme Form where Known, Biological Functions...

Vitamin Coenzyme Form Metabolic Role and/or Associated Deficiency Disease RDA... 

The munber and chemical variety of vitamin coenzyme forms, and the instability of many of their reduced forms, have made it difficult to separate and quantify vitamins in complex mixtures. In general, crystalline water-soluble vitamins are relatively stable in the presence of air, whereas in solution some are easily oxidized. They are generally most stable in acidic media, and least stable in alkaline ones (Table 1). Their degradation in solution is further dependent on the temperature, the presence or absence of oxygen, and the presence or absence of metal ions. Biological... 

It is recognized that there are several important forms of vitamin The active coenzyme forms are adenosylcobalamin [13870-90-1] (coenzyme... 

FIGURE 18.28 The structure of cyanocobalamin (top) and simplified structures showing several coenzyme forms of vitamin Bi2- The Co—C bond of 5 -deoxyadenosylcobalamin is predominantly covalent (note the short bond length of 0.205 nm) but with some ionic character. Note that the convention of writing the cobalt atom as Co" " attributes the electrons of the Co—C and Co—N bonds to carbon and nitrogen, respectively. 

Vitamin B1. Figure 1 Structure of thiamin and its coenzyme form thiaminpyrophosphate (TPP). 

Certain groups of organocobalt(III) complexes have been dealt with in previous reviews. The organo-corrinoids have been mentioned in all reviews on vitamin B, 2 since 1961, when the coenzyme form was identified as an organometallic compound [see, for example, (79, 178) and references therein]. The literature on the corrinoids is too extensive to be treated comprehensively here and for details and references readers are referred to the book on The Inorganic Chemistry of Vitamin B,2 (136)certain other aspects of the organometallic chemistry of cobalt corrinoids are treated elsewhere (137). The pentacyanides were reviewed in 1967 (105), the DMG complexes (cobaloximes) in 1968 (145), and some aspects of salen, BAE, and related complexes in 1970 (17). 

In 1958 Barker (20) isolated a red, heat stable, light labile, cofactor which was required for the metabolism of glutamate in cell-extracts of Clostridium tetanomorphum. Subsequently this cofactor was crystallized. X-ray crystallography identified Barker s cofactor as the coenzyme form of Vitamin B12 (15, 21). 

The recent review on vitamin Bi2 in this series (G18) provides an excellent survey. In current research emphasis is placed on the biosynthesis and the coenzyme forms of vitamin Bi2 (R2). Similarity between biosynthesis of porphyrin and vitamin Bi2 was shown by the incorporation of 6 -aminolevulic acid into the vitamin by a microorganism (S4). The l-amino-2-propanol moiety of vitamin Bj2 may be formed by decarboxylation of threonine (K10). Nothing is yet known about the nature of the precursors of the dimethylbenzimidazole portion of vitamin Bi2. 

Knowledge of the coenzyme forms of vitamin Bi2 has increased steadily. The first coenzyme of Bi2 isolated from bacteria had similarities to pseudovitamin Bi2 it contained adenylic acid instead of 5,6-dimethyl-benzimidazole, but differed in lacking cyanide and having an extra molecule of adenine which was assumed to be bound to the cobalt atom by the coordination site, often occupied by cyanide (B24). This coenzyme, adenylcobamide, was completely inactive for Ochromonas malhamensis, but active for Escherichia coli 113-3. 

Thiazoles play a prominent role in nature. For example, the thiazolium ring present in vitamin Bi serves as an electron sink and its coenzyme form is important for the decarboxylation of a-keto-acids. Furthermore, thiazoles are useful building blocks in pharmaceutical agents as exemplified by 2-(4-chlorophenyl)thiazole-4-acetic acid, a synthetic anti-inflammatory agent. 

Not all vitamin coenzymes need to be in the form of a nucleotide (base, sugar, phosphate). For example thiamine biotin pyridoxine vitamin B12. 

This group includes the coenzyme forms of water-soluble vitamin B2 or riboflavin. Synthesis occurs by initial cyclohydrolase action on the guanine ring of GTP and subsequent steps lead to the synthesis of the isoalloxazine ring structure (see structures below). 

Vitamin deficiency of Bj leads to the disease known as Beriberi. However, nowadays in the Western hemisphere, vitamin Bj deficiency is mainly found as a consequence of extreme alcoholism. In fact, the vitamin absorption by the gut is decreased and its excretion is increased by alcohol. Alcohol also inhibits the activation of vitamin Bj to its coenzyme form, thiamine pyrophosphate ester (TPP). There is no evidence of adverse effects of oral intake of thiamine [417]. The main food sources of vitamin Bj are lean pork, legumes, and cereal grains (germ fraction). It is soluble in water and stable at higher temperature and at pH lower than 5.0, but it is destroyed rapidly by boiling at pH 7.0 or above. 

Methylcobalamin is the coenzyme form of vitamin It is neurologically active, most bioavailable and best utilized. Unlike cyanocobalamin, it does not require any conversion after absorption by the body and is better retained by the liver and other tissues. It has exhibited beneficial effects against brain aging, irregular sleep patterns. It supports immune function and promote normal cell growth. It represents one of the best values in nutritional products, given its comparably low cost and its wide range of potential benefits. 

All aminotransferases have the same prosthetic group and the same reaction mechanism. The prosthetic group is pyridoxal phosphate (PLP), the coenzyme form of pyridoxine, or vitamin B6. We encountered pyridoxal phosphate in Chapter 15, as a coenzyme in the glycogen phosphorylase reaction, but its role in that reaction is not representative of its usual coenzyme function. Its primary role in cells is in the metabolism of molecules with amino groups. 

Structure of vitamin B12 (cyanocobalamin) and its coenzyme forms (methylcobalamin and 5 -deoxyadenosyl-cobalamin). 

Biochemically, PLP is the coenzyme form of vitamin B6. As such it participates in many enzymatic reactions involved in amino acid biosynthesis and catabolism. Specific examples include ... 

There are two biologically active coenzyme forms of vitamin Bl2, MeCbl and AdoCbl (167,168). 

In this chapter we are concerned, not primarily with vitamins per se, but with coenzymes. Many coenzymes are modified forms of vitamins. The modifications take place in the organism after ingestion of the vitamins. Coenzymes act in concert with enzymes to catalyze biochemical reactions. Tightly bound coenzymes are sometimes referred to as prosthetic groups. A coenzyme usually functions as a major component of the active site on the enzyme, which means that understanding the mechanism of coenzyme action usually requires a complete understanding of the catalytic process. 

Pyridoxal-5 -phosphate is the coenzyme form of vitamin B6, and has the structure shown in figure 10.3. The name vitamin B6 is applied to any of a group of related compounds lacking the phosphoryl group, including pyridoxal, pyridoxamine, and pyridoxine. 

S-Methylmalonyl-CoA mutase (EC 5.4.99.2) is a deoxyadenoxyladen-osylcobalamin-dependent enzyme of mitochondria required to catalyze the conversion of methylmalonyl-CoA to succinyl-CoA. A decrease in the activity of methylmalonyl-CoA mutase leads to the urinary excretion of large amounts of methylmalonic acid (C22). The biochemical lesion may be at the mutase level due to an abnormality of apoenzyme protein or an inability to elaborate the required coenzyme form of vitamin B12> i.e., adenosyl-cobalamin. In rare cases the abnormality may be due to an inability to convert the d form of methylmalonyl-CoA mutase to the l form as a result of a defective racemase (EC 5.1.99.1) (Kll). In patients, the nature of the abnormality can be determined by tissue culture studies (D13) and by clinical trial, since patients with a defect in adenosylcobalamin production will show clinical improvement when treated with very large doses of vitamin B12 (Mil). 

This is another rare inherited disorder of vitamin B12 metabolism in which both coenzyme forms, adenosylcobalamin and methylcobalamin, are affected. Methylcobalamin is required for the transfer of the methyl group of 5-methyltetrahydrofolate to homocysteine to give methionine. Lack of methylcobalamin results in deficient activity of 2V5-methyltetrahydrofolate-homo-cysteine methyltransferase, resulting in a reduced ability to methylate homocysteine. A failure of methionine synthetase would produce a similar result. 

The terms cofactor, coenzymes, and prosthetic group are used to describe the nonprotein moieties of the enzyme active center. The distinction between these terms is not sharp. Some of the cofactors are derivatives of vitamins that form either covalent or noncovalent linkages at or near the active site of the enzyme, and some are metal ions. If a cofactor (coenzyme) is tightly bound to the protein moiety (the apoenzyme), it is often referred to as a prosthetic group. A coenzyme that is easily removed from the holoenzyme, leaving behind the apoenzyme, is often regarded as a second substrate. 

Vitamins are essential in mammalian physiology because their coenzyme forms are prosthetic groups or cofactors in many enzyme reactions or because they can perform certain specialized functions in the human organism. Vitamin A and its role in the visual process is an example. The biology of vitamins may be examined from the nutritional or biochemical points of view. The former is concerned with minimum daily requirements, dietary sources, bioavailability, and deficiency syndromes. The biochemist looks for structures, functional groups, conversion to coenzymes, mechanisms of action, mode of transport, and storage. Both aspects will be addressed in this chapter, though the emphasis will be on the biochemical properties of vitamins. 

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