Vitamin reactions requiring

FIGURE 6.17 Hydroxylation of proUne residnes is catalyzed by prolyl hydroxylase. The reaction requires -ketoglntarate and ascorbic acid (vitamin C). 

Factor XIa in the presence of activates factor IX (55 kDa, a zymogen containing vitamin K-dependent y-carboxyglutamate [Gla] residues see Chapter 45), to the serine protease, factor IXa. This in turn cleaves an Arg-Ile bond in factor X (56 kDa) to produce the two-chain serine protease, factor Xa. This latter reaction requires the assembly of components, called the tenase... 

Note that this overall reaction requires three coenzymes that we encountered as metabolites of vitamins in chapter 15 NAD+, derived from lucotiiuc acid or nicotinamide FAD, derived from riboflavin and coenzyme A(CoASH), derived from pantothenic acid. In the overall process, acetyl-SCoA is oxidized to two molecules of carbon dioxide with the release of CoASH. Both NAD+ and FAD are reduced to, respectively, NADH and FADH2. Note that one molecule of guanosine triphosphate, GTP, functionally equivalent to ATP, is generated in the process. 

The pyruvate carboxylase reaction requires the vitamin biotin (Fig. 16-16), which is the prosthetic group of the enzyme. Biotin plays a key role in many carboxyla-tion reactions. It is a specialized carrier of one-carbon groups in their most oxidized form C02. (The transfer of one-carbon groups in more reduced forms is mediated by other cofactors, notably tetrahydrofolate and 5-adenosylmethionine, as described in Chapter 18.)... 

Oxidation of fatty acids with an odd number of carbons proceeds two carbons at a time (pro ducing acetyl CoA) until the last three carbons (propionyl CoA). This compound is con verted to methylmalonyl CoA (a reaction requiring biotin), which is then converted to succinyl CoA by methylmalonyl CoA mutase (requiring vitamin B )- A genetic error in the mutase or vitamin B12 deficiency causes methylmalonic acidemia and aciduria. 

Utilization of an oxygen nucleophile gives similar results (Scheme 8E.35). Whereas modest enantioselectivities (7-54% ee) have been recorded with various ligands [177], the use of 5 results in the efficient cyclization of phenol to furnish the nucleus of tocopherol (vitamin E) with 86% ee [178], Extension of this methodology to intermolecular reactions requires control of regiochemistry, a problem that is not present in the corresponding intramolecular... 

Vitamin C [ascorbic acid) Men 90 mg/d Women 75 mg/d Cofactor for reactions requiring reduced copper or iron met-alloenzyme and as a protective antioxidant prevents scurvy Gastrointestinal disturbances, kidney stones, excess iron absorption... 

In this transformation, l-G1u can be replaced by L-Asp, i-Om, or by other amino acids the reaction requires the presence of pyridoxal-5-phosphate (vitamin B ), or, thiamine (vitamin Bi) [39, 40], as coenzyme. 

Gamma carboxylation of glutamic acid residue in a protein. This is an enzymic reaction catalyzed by a carboxylase to modify a glutamic acid residue of a protein to form qamma-carboxyqlutamic acid. The carboxylase reaction requires vitamin K, 02, and C02. 

Although the fatty acid oxidation scheme works neatly for even-numbered chain lengths, it can t work completely for fatty acids that contain an odd number of carbons. P-oxidation of these compounds leads to propionyl-CoA and acetyl-CoA, rather than to two acetyl-CoA at the final step. The propionyl-CoA is not a substrate for the TCA cycle or other simple pathways. Propionyl-CoA undergoes a carboxylation reaction to form methylmalonyl-CoA. This reaction requires biotin as a cofactor, and is similar to an essential step in fatty acid biosynthesis. Methylmalonyl-CoA is then isomerized by an epimerase and then by methylmalonyl-CoA mutase—an enzyme that uses Vitamin Bi2 as a cofactor—to form succinyl-CoA, which is a TCA-cycle intermediate. 

Although numerous enzymatic reactions requiring vitamin B12 have been described, and 10 reactions for adenosylcobalamin alone have been identified, only three pathways in man have so far been recognized, one of which has only recently been identified (PI). Two of these require the vitamin in the adenosyl form and the other in the methyl form. These cobalamin coenzymes are formed by a complex reaction sequence which results in the formation of a covalent carbon-cobalt bond between the cobalt nucleus of the vitamin and the methyl or 5 -deoxy-5 -adenosyl ligand, with resulting coenzyme specificity. Adenosylcobalamin is required in the conversion of methylmalonate to succinate (Fig. 2), while methylcobalamin is required by a B12-dependent methionine synthetase that enables the methyl group to be transferred from 5-methyltetrahydrofolate to homocysteine to form methionine (Fig. 3). 

Thankfully, as the quote points out, formate is not just floating around in solution. It is first attached to a vitamin called THF, a cousin of the B vitamin folic acid (don t even ask how the vitamin is synthesized). When it is attached by an enzyme to the vitamin (in a reaction requiring an energy pellet of ATP), formate is revved up and made ready for action. The THF-formate complex, however, would not join up with Intermediate IV to give Intermediate V unless directed to do so by Enzyme IV it would float away in the cell until it reacted with something else or decayed, and that would mess up our synthesis of AMP. That doesn t happen, however, because the enzyme guides the reaction to the correct products. 

The linking of two building blocks to form a double bond under the conditions of the Wittig reaction required that one of the building blocks has phosphorus ylide functionality and that the other has carbonyl functionality. The appropriate C5 building block for vitamin A can thus be either l-triphenyl-2-methyl-4-hydroxy-2-butenylidenephosphorane (26) 9) or P-formylcrotyl alcohol (2-methyl-4-hydroxy-2-butenal) (8 a). 

Various vitamin B12 derivatives are shown in Figure 6.2, where the R group is usually taken as CN-. This form of vitamin B12 is cyanocobalamin. In the active coenzyme, the CN" is replaced by a 5 -deoxyriboadenosyl residue or by -CH3. Vitamin B12 seems to be the only mammalian substance that contains cobalt. It also has a unique corrin ring structure, which is very similar to that of heme. Metabolic reactions requiring vitamin B12 are discussed in Chapters 19 and 20. 

Figure 28-5. The reaction catalyzed by methionine synthase, a vitamin B12-requiring enzyme. In this reaction, homocystine is converted to methionine, with the simultaneous production of tetrahydrofolate (THF) from 5-methyltetrahydrofolate.Methionine can then be converted to 5-adenosyhnethionine (SAM), the universal methyl-group donor.

Ascorbate cataboUsm is increased in subjects with iron overload, probably as a result of nonenzymic reactions with bon that is not protein-bound. The transferrin polymorphisms that are associated with susceptibiUty to iron overload result in higher vitamin C requirements for those subjects with high iron status (Kasvosve et al., 2002). 

Pro-Pro- repeat is shown in Figure 9-22. Hydroxyproline units are formed by adding a hydroxyl group, -OH, to proiine after thej collagen chain is built. This reaction requires 1 vitamin C, which our bodies cannot make. Hydroxyproline is critical for collagen stability, so if we don t get enough vitamin C iii j our diet, the results can be disastrous. (You get scurvy, which initially results in loss of teeth and easy bruising, because your body can t repair the wear-and-tear of everyday life.)... 

The second reaction requiring vitamin B12 catalyzes the conversion of homocysteine to methionine and is catalyzed by methionine synthase. This reaction results in the transfer of the methyl group from N -methyltetrahydrofolate to hydroxycobalamin generating tetrahydrofolate and methylcobalamin during the process of the conversion. 

The most important reaction requiring ascorbate as a cofactor is the hydroxylation of proline residues in collagen. Vitamin C is, therefore, required for the maintenance of normal connective tissue as well as for wound healing since synthesis of connective tissue is the first event in wound tissue remodeling. 

Several other metabolic reactions require vitamin C as a cofactor. These include the catabolism of tyrosine and the s)mthesis of epinephrine from tyrosine and the synthesis of the bile acids. 

FIGURE 2.40 The major pathway for taurine biosynthesis in the liver- First, cy teine is converted to cysteine sulfinic acid in an oxygen-requiring reaction catalyzed by an iron metalloeozyme- The second step, catalyzed by a vitamin B -requiring enzyme, is a decarboxylation reaction. The final step appears to be catalyzed by a copper metaLloenzyme and to require oxygen. Apparently, about one-fourth of the cysteine in the liver eventually is converted to taurine. 

Each of the following vitamins is required for reactions in the oxidation of pyruvate to COz and HzO EXCEPT... 

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