Pyridoxamine structure

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. 

Protein ALBP-PX was the first pyridoxamine-conjugated protein to be synthesized and structurally characterized. Under single-turnover conditions, this protein demonstrated amino acid production rates of only 56% of the free cofactor. However, depending on the nature of the a-keto acid, ALBP-PX did show a range of optical inductions for the amino acid product. Notably, enantiomeric excesses in the order of 94% were observed for the production of valine. Additionally, several trends were noted. All amino acid products that showed optical induction favored the 1-enantiomer, except alanine, which favored the d-enantiomer. Furthermore, a-keto acids with branched side chains... 

Numerous examples of modiflcations to the fundamental cyclodextrin structure have appeared in the literature.The aim of much of this work has been to improve the catalytic properties of the cyclodextrins, and thus to develop so-called artificial enzymes. Cyclodextrins themselves have long been known to be capable of catalyzing such reactions as ester hydrolysis by interaction of the guest with the secondary hydroxyl groups around the rim of the cyclodextrin cavity. The replacement, by synthetic methods, of the hydroxyl groups with other functional groups has been shown, however, to improve remarkably the number of reactions capable of catalysis by the cyclodextrins. For example, Breslow and CO workersreported the attachment of the pyridoxamine-pyridoxal coenzyme group to beta cyclodextrin, and thus found a two hundred-fold acceleration of the conversion of indolepyruvic acid into tryptophan. 

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. 

When pyridoxamine with a dipolar ionic ring structure (Fig. 14-9) and an absorption peak at 30,700 cm-1 (326 ran) is irradiated, fluorescence emission is observed at 25,000 cm 1 (400 ran). When basic pyridoxamine with an anionic ring structure and an absorption peak at 32,500 cm 1 (308 nm) is irradiated, fluorescence is observed at 27,000 cm-1 (370 nm), again shifted 5500 cm 1 from the absorption peak. However, when the same molecule is irradiated in acidic solution, where the absorption peak is at 34,000 cm 1 (294 nm), the luminescent emission at 25,000 cm 1 is the same as from the neutral dipolar ionic form and abnormally far shifted (9000 cm ) from the 34,000 cm-1 absorption peak.185186 The phenomenon, which is observed for most phenols, results from rapid dissociation of a proton from the phenolic group in the photoexcited state. A phenolic group is more acidic in the excited state than in the ground state, and the excited pyridoxamine cation in acid solution is rapidly converted to a dipolar ion. 

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... 

Zinc complexes of a range of pyridone defleecing agents have been described.535 A number of pyridoxamine(77) complexes have been reported536,537 and a crystal structural analysis of the complex ZnL2(OH2)2 (78) (HL = 77) has been performed.537... 

In 1934, Gyorgy cured a dermatitis in rats (not due to vitamins Bj or B2) with a yeast extract factor, In 1938, Lepkovsky isolated a similar factor from nee bran extract. In that same year. Keresztesy and Stevens isolated and crystallized pure (, from rice polishings. Also, in the same year, Kohn, Wendt, and Westphal synthesized pyridoxine and gave pyridoxine its present name. In the following year (1939). Stiller, Keresztesy, and Stevens established the structure of the vitamin, In 194 5, Snell observed pyridoxal and pyridoxamine. The recognition of and establishment of B5 requirements in humans was not achieved until 1953, by Snyderman et al. 

Richardson et al.y as part of a study of the reactions of metal ions with vitamins, have determined the structures of the bis chelates of pyridoxamine (PM) with Cu1111 and Zn11.12 In each case the pyridoxamine molecule behaves as an N—O bidentate in bonding through the 4-(aminomethyl) and phenolate groups. The PM molecules are zwitterionic, with the heterocyclic N atoms protonated. 

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). 

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

Figure 2.5 Structure of the PEI-pyridoxamine systems. (Reprinted from Ref. 36. Copyright 2002 American Chemical Society.)...

Figure S.8 Stereo view showing positions 60, 72, 104 and 117 in IFABP that have been used for the attachment of pyridoxamine and other catalytic groups. From top to bottom A104, Y117, L72 and V60. Color scheme Protein secondary structure (green), carbon (white), oxygen (red), nitrogen (blue).

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