Niacin biosynthesis

These observations are consistent with the current notion of uniqueness in certain biochemical trends during the evolution of the fungi. In addition to the situation involving TS, the fungi possess distinct pathways for lysine and niacin biosynthesis and thereby reflect distinct divergence from the bacteria and higher plant biochemical patterns. 

Pyridoxamine phosphate serves as a coenzyme of transaminases, e.g., lysyl oxidase (collagen biosynthesis), serine hydroxymethyl transferase (Cl-metabolism), S-aminolevulinate synthase (porphyrin biosynthesis), glycogen phosphoiylase (mobilization of glycogen), aspartate aminotransferase (transamination), alanine aminotransferase (transamination), kynureninase (biosynthesis of niacin), glutamate decarboxylase (biosynthesis of GABA), tyrosine decarboxylase (biosynthesis of tyramine), serine dehydratase ((3-elimination), cystathionine 3-synthase (metabolism of methionine), and cystathionine y-lyase (y-elimination). 

Nicotinate and nicotinamide, together referred to as niacin, are required for biosynthesis of the coenzymes nicotinamide adenine dinucleotide (NAD"") and nicotinamide adenine dinucleotide phosphate (NADP" ). These both serve in energy and nutrient metabolism as carriers of hydride ions (see pp. 32, 104). The animal organism is able to convert tryptophan into nicotinate, but only with a poor yield. Vitamin deficiency therefore only occurs when nicotinate, nicotinamide, and tryptophan are all simultaneously are lacking in the diet. It manifests in the form of skin damage (pellagra), digestive disturbances, and depression. 

Riboflavin (vitamin Bj) is chemically specified as a 7,8-dimethyl-10-(T-D-ribityl) isoalloxazine (Eignre 19.22). It is a precnrsor of certain essential coenzymes, such as flavin mononucleotide (FMN) and flavin-adenine dinucleotide (FAD) in these forms vitamin Bj is involved in redox reactions, such as hydroxylations, oxidative carboxylations, dioxygenations, and the reduction of oxygen to hydrogen peroxide. It is also involved in the biosynthesis of niacin-containing coenzymes from tryptophan. 

Precursors in the biosynthesis of niacin In animals and bacteria, tryptophan and in plants, glycerol and succinic acid. Intermediates in the synthesis include kynurenine, hydroxyanthranilic acid, and quinolinic acid. In animals, the niacin storage sites are liver, heart, and muscle. Niacin supplements are prepared commercially by (1) Hydrolysis of 3-cyanopyndine or (2) oxidation of nicotine, quinoltne, or collidine. 

Several of the B vitamins function as coenzymes or as precursors of coenzymes some of these have been mentioned previously. Nicotinamide adenine dinucleotide (NAD) which, in conjunction with the enzyme alcohol dehydrogenase, oxidizes ethanol to ethanal (Section 15-6C), also is the oxidant in the citric acid cycle (Section 20-10B). The precursor to NAD is the B vitamin, niacin or nicotinic acid (Section 23-2). Riboflavin (vitamin B2) is a precursor of flavin adenine nucleotide FAD, a coenzyme in redox processes rather like NAD (Section 15-6C). Another example of a coenzyme is pyri-doxal (vitamin B6), mentioned in connection with the deamination and decarboxylation of amino acids (Section 25-5C). Yet another is coenzyme A (CoASH), which is essential for metabolism and biosynthesis (Sections 18-8F, 20-10B, and 30-5A). 

Nutritionally, humans derive their pyridoxal coenzyme from vitamin B6. Most symptoms of vitamin Be deficiency apparently result from the involvement of the coenzyme in the biosynthesis of neurotransmitters and the niacin group of NAD and NADPH rather than from amino acid deficiency. 

It is clear from Equation (19.4) that saturated fat, not cholesterol, is the single most important factor that raises serum cholesterol. Some cases of hyperlipoproteinemia type IV (high VLDL) respond to low-carbohydrate diets, because the excess of VLDL comes from intestinal cells, where it is produced from dietary carbohydrate. Resins, such as cholestyramine and cholestipol, bind and cause the excretion of bile salts, forcing the organism to use more cholesterol. Lovastatin decreases endogenous cholesterol biosynthesis (see later), and niacin (nicotinic acid) apparently decreases the production of VLDL and, consequently, LDL. It also results in an HDL increase. Antioxidants that inhibit the conversion of LDL to oxidized LDL have also been used with some success. These are high doses of vitamin E and the drug probucol. 

Some of the vitamins in the coeiizymc form associate tightly wdth specific enzymes, but not via a covalent linkage. Immediately after biosynthesis on the ribosome, enzymes do itot contain their cofactor, and these are called apoenzymes. An eitzyme containing its required cofactor is called a hoLoenzyme, With removal of the cofactor, the enzyme is also called an apoenzyme. The enzymes that exist in apoenzyme and holoenzyme forms include those that use vitamin Bx2, vitamin B, thiamin, and riboflavin-based cofactors. Enzymes that use niacin-based cofactors, folate, ascorbate, and vitamin K are not said to exist in apoenzyme and holocn-zyme forms. These enzymes bind their cofactors relatively weakly, and the cofactors behave in a manner similar to substrates. 

NAD tends to be an electron acceptor in catabolic reactions involving the degradation of carbohydrates, fatty acids, ketone bodies, amino acids, and alcohol. NAD is used in energy-producing reactions. NADP, which is cytosolic, tends to be involved in biosynthetic reactions. Reduced NADP is generated by the pentose phosphate pathway (cytosolic) and used by cytosolic pathways, such as fatty acid biosynthesis and cholesterol synthesis, and by ribonucleotide reductase. The niacin coenzymes are used for two-electron transfer reactions. The oxidized form of NAD is NAD". There is a positive charge on the cofactor because the aromatic amino group is a quaternary amine. A quaternary amine participates in four... 

Nishizuka Y. and Hayaishi, O., Studies on the biosynthesis of nicotinamide adenine dinucleotide. I. Enzymatic synthesis of niacin ribonucleotides from 3-hydroxy-anthranilic in mammalian tissues, J. Biol. Chem., 238, 3369, 1963. 

Nicotinamide adenine dinucleotide (NAD) is the coenzyme form of the vitamin niacin. Most biochemical reactions require protein catalysts (enzymes). Some enzymes, lysozyme or trypsin, for example, catalyze reactions by themselves, but many require helper substances such as coenzymes, metal ions, and ribonucleic acid (RNA). Niacin is a component of two coenzymes NAD, and nicotinamide adenine dinucleotide phosphate (N/kDP). NAD (the oxidized form of the NAD coenzyme) is important in catabolism and in the production of metabolic energy. NADP (the oxidized form of NADP) is important in the biosynthesis of fats and sugars. 

The pyridine ring plays a key role in several biological processes, most notably in the oxidation/reduction coenzyme nicotine adenine dinucleotide (NADP) the vitamin niacin (or the corresponding acid) is required for its biosynthesis. Pyridoxine (vitamin Bg) plays a key role as the coenzyme in transaminases. Nicotine, a highly toxic alkaloid, is the major active component in tobacco, and the most addictive drug known. ... 

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