Tryptophan nicotinamide ring

Niacin was discovered as a nutrient during studies of pellagra. It is not strictly a vitamin since it can be synthesized in the body from the essential amino acid tryptophan. Two compounds, nicotinic acid and nicotinamide, have the biologic activity of niacin its metabolic function is as the nicotinamide ring of the coenzymes NAD and NADP in oxidation-reduction reactions (Figure 45-11). About 60 mg of tryptophan is equivalent to 1 mg of dietary niacin. The niacin content of foods is expressed as mg niacin equivalents = mg preformed niacin + 1/60 X mg tryptophan. Because most of the niacin in cereals is biologically unavailable, this is discounted. 

Neurotoxins produced by the body. Some normal body constituents are neurotoxic in excess. These incluse quinolinic acid (Fig. 25-11),889 3-hydroxykynurenine (Fig. 25-11 p. 1444),890 and homocysteine.891 Elevated levels of homocysteine are also associated with vascular disease and stroke (Chapter 24). 3-Hydroxykynurenine is a precursor to ommochrome pigments of insects and an intermediate in conversion of tryptophan into the nicotinamide ring of NAD in humans (Fig. 25-11). 6-Hydroxydopamine (Fig. 30-26), which may be formed in the body, is severely toxic to catecholaminergic neurons.892... 

Figure 8.1). Although the amino acid tryptophan is quantitatively the major precursor of the nicotinamide ring of the coenzymes (Section 8.3), it is not considered to he a niacin vitamer.

Purines and pyrimidines are derived largely from amino acids. The biosynthesis of these precursors of DNA, RNA, and numerous coenzymes will be discussed in detail in Chapter 25. The reactive terminus of sphingosine, an intermediate in the synthesis of sphingolipids, comes from serine. Histamine, a potent vasodilator, is derived from histidine by decarboxylation. Tyrosine is a precursor of the hormones thyroxine (tetraiodothyronine) and epinephrine and of melanin, a complex polymeric pigment. The neurotransmitter serotonin (5-hydroxytryptamine) and the nicotinamide ring of NAD + are synthesized from tryptophan. Let us now consider in more detail three particularly important biochemicals derived from amino acids. 

The nicotinamide ring of NAD+ is derived from the vitamin niacin (nicotinic acid). It is also produced to a limited extent from the amino acid tryptophan. 

A 70-B. Although dietary niacin is the major source of the nicotinamide ring of NAD, it may also be produced from tryptophan. 

In contrast to prokaryotes, in mammals, tryptophan is not synthesized in the body and, therefore, must be provided through a dietary source. The essential amino acid is not only a building block of proteins but also a precursor of serotonin and of the nicotinamide ring of NAD+. 

Quenching of the protein fluorescence of LADH has been observed by bound aromatic inhibitors and NADH (194-198). Possible causes of this quenching have been discussed mainly in terms of two alternative processes either a change in the environment of the tryptophans or an excitation energy transfer process from tryptophan to the nicotinamide ring of the coenzyme. The first alternative is highly unlikely since... 

Distances in A from Nicotinamide Ring in the Red Subunit to All Tyrosines and Tryptophans in the Molecule"... 

The nicotinamide ring of NAD can be synthesized in the body from the essential amino acid tryptophan, as shown in Figure 11.13. In adults, almost all of the dietary intake of tryptophan is metabolized by this pathway and hence is potentially available for NAD synthesis. 

Humans express at least three forms of A-methyltransferase that are catago-rized base upon substrate specificity. Nicotinamide A-methyltransferase methylates compounds that have an indole ring such as serotonin and tryptophan or a pyridine... 

B. The ring portion of tryptophan may be converted to the nicotinamide moiety of NAD, which may also be derived from the vitamin niadn. 

A bicyclic nitrogenous aromatic ring system (known as an indole ring) is attached to the /6-carbon of alanine to form the R-group of tryptophan. Tryptophan is a precursor of serotonin, melatonin, nicotinamide, and many... 

Fig. 39.19. Degradation of tryptophan. One of the ring carbons produces formate. The nonring portion forms alanine. Kynurenine is an intermediate, which can be converted to a number of urinary excretion products (e.g., xanthurenate), degraded to CO2 and acetyl CoA, or converted to the nicotinamide moiety of NAD and NADP, which also can be formed from the vitamin niacin.

A further important pathway of L-tryptophan metabolism also diverges from 2-amino-3-carboxy-m, cis muconic semi-aldehyde (26) the ring fission product of 3-hydroxyanthranilate (25) and this is the biosynthetic pathway which leads to the formation of the pyridine ring of the nicotinamide nucleotides . The first step in this pathway appears to be the recyclisation of the oxidation product (26) to give quinolinic add (27) which is transformed to the pyridine nucleotides, such as NAD (28) in a complex series of reactions. Figure 4.6. 

The catabolism of tryptophan seems to have many steps in common with the formation of nicotinamide. The amino nitrogen is not attacked initially, but instead the indole ring is opened up by tryptophan pyrrolase (an iron-porphyrin enzyme). Just as in other cases of oxidative ring opening (cf. Chapt. X-7), the double bond is split and each new end receives one oxygen atom. In this way N-formylkynurenine is formed it is then hydrolyzed to formate and kynurenine. 

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