Pyridoxamine phosphate , structure

Fig. 4. Structures of (a) pyridoxine (vitamin Bg), (b) pyridoxal phosphate and (c) pyridoxamine phosphate.

Vitamin B Three substances are classed under the term pyridoxine or adermine pyridoxol, pyridoxal and pyridoxamine. Pyridoxine was isolated by various study groups in 1938. Its structure was described by Folkers and Kuhn in 1939. Pyridoxal and pyridoxamine were discovered by Snell in 1942. Pyridoxal phosphate and pyridoxamine phosphate are biologically active substances. Intestinal absorption of Bg is dose-dependent and not limited. In alcoholism, a deficiency of vitamin Bg is encountered in 20—30% of cases, whereas the respective percentage is 50—70% in alcoholic cirrhosis. Vitamin Bg is an important coenzyme for transaminases, which transfer amino groups from amino adds to keto acids. In this way, biochemical pathways between the dtiic acid cycle and carbohydrate and amino acid metabolisms are created. (104)... 

Recognize the structures of pyridoxal phosphate (PLP) and pyridoxamine phosphate (PMP), indicate the reactive functional groups on each, and name the dietary precursor of PLP. 

Fig. 14-3 Structures of pyridoxal phosphate (left) and pyridoxamine phosphate (right).

Karrer and Viscontini synthesized the acetal of pyridoxal-3-phosphate and claimed that it had codecarboxylase activity but could not reactivate a transaminase system. In the meantime, Gunsalus presented evidence that the active synthetic product was not the 3-phosphate (and by elimination must be the 5-phosphate). This discrepancy was resolved when the two products were compared simultaneously on the same test system. The activity of the 3-phosphate was so low compared to the active pyridoxal phosphate that the 3-phosphate was definitely ruled out as the active coenzyme. In a recent series of papers,the structure of pyridoxal phosphate is definitely established as pyridoxal-5-phosphate and that of pyridoxamine-phosphate as the 5 phosphate. 

Chemistry— Vitamin B-6 is found in foods in three forms which are readily interconvertible—pyridoxine, pyridoxal, and pyridoxamine. Also vitamin B-6 is found in physiological systems in the forms of pyridoxal phosphate and pyridoxamine phosphate. The structural formulas of the three naturally occurring free forms of these compounds are given in Fig. V-30. 

Vitamin B6. Figure 1 Structure of pyridoxin, pyridoxal, pyridoxamine, and the coenzymes pyridoxal-5 -phosphate and pyridoxamine-5Y-phosphate. 

FIGURE 10.2 Structural formula of vitamin and related compounds. 1 — pyridoxine, 2 — pyridoxal, 3 — pyridoxamine, 4 — 4-pyridoxic acid 5 — pyridoxal-5 -phosphate. 

The terminology vitamin Bg covers a number of structurally related compounds, including pyridoxal and pyridoxamine and their 5 -phosphates. Pyridoxal 5 -phosphate (PLP), in particular, acts as a coenzyme for a large number of important enzymic reactions, especially those involved in amino acid metabolism. We shall meet some of these in more detail later, e.g. transamination (see Section 15.6) and amino acid decarboxylation (see Section 15.7), but it is worth noting at this point that the biological role of PLP is absolutely dependent upon imine formation and hydrolysis. Vitamin Bg deficiency may lead to anaemia, weakness, eye, mouth, and nose lesions, and neurological changes. 

Vitamin B6 occurs naturally in three related forms pyridoxine (6.26 the alcohol form), pyridoxal (6.27 aldehyde) and pyridoxamine (6.28 amine). All are structurally related to pyridine. The active co-enzyme form of this vitamin is pyridoxal phosphate (PLP 6.29), which is a co-factor for transaminases which catalyse the transfer of amino groups (6.29). PLP is also important for amino acid decarboxylases and functions in the metabolism of glycogen and the synthesis of sphingolipids in the nervous system. In addition, PLP is involved in the formation of niacin from tryptophan (section 6.3.3) and in the initial synthesis of haem. 

Observation of an abnormally large shift in the position of fluorescent emission of pyridoxal phosphate (PLP) in glycogen phosphorylase answered an interesting chemical question.187188 A 330 nm (30,300 cm ) absorption band could be interpreted either as arising from an adduct of some enzyme functional group with the Schiff base of PLP and a lysine side chain (structure A) or as a nonionic tautomer of a Schiff base in a hydrophobic environment (structure B, Eq. 23-24). For structure A, the fluorescent emission would be expected at a position similar to that of pyridoxamine. On the other hand, Schiff bases of the... 

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. 

Pyridoxine, pyridoxal, and pyridoxamine, which occur in foodstuffs, are collectively known as vitamin Bg. In the body, all three are converted to pyridoxal phosphate which is the coenzyme for amino-acid decarboxylase and for transaminase. The structures of the three active forms of vitamin Bg and the pyridoxal phosphate, are shown below (55). 

The final step in this pathway is the oxidation of PNP to PLP and is carried out by PdxH. Tbe recombinant enzyme from E. coli has been studied in vitro and is a 51 kDa homodimer that utilizes flavin mononucleotide (FMN) as a cofactor. PdxH can use either PNP or pyridoxamine 5 -phosphate (PMP) as a substrate with a of 2 and 105 pM and cat of 0.8 and 1.7 s for PNP and PMP, respectively. The structures of the enzyme from E. coli as well as homologues from Mycobacterium tuberculosis and humans have been solved. The E. coli enzyme with PLP and FMN bound is shown in Figure 6. PdxH is involved in both the biosynthetic and the salvage pathways and is further discussed in a section describing the transport, salvage, and interconversion of the various forms of vitamin Bg. 

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