Amino acid decarboxylation

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. 

An important example of PLP-dependent amino acid decarboxylation is the conversion of histidine into histamine. Histamine is often involved in human allergic responses, e.g. to insect bites or pollens. Stress stimulates the action of the enzyme histidine decarboxylase and histamine is released from mast cells. Topical antihistamine creams are valuable for pain relief, and oral antihistamines are widely prescribed for nasal allergies such as hay fever. Major effects of histamine include dilation of blood vessels, inflammation and swelling of tissues, and narrowing of airways. In serious cases, life-threatening anaphylactic shock may occur, caused by a dramatic fall in blood pressure. 

Mechanism of action of amino acid decarboxylation proposed. 18, 19... 

Amino acid decarboxylation takes place by the removal of the a-carboxyl group to give the corresponding amine. Two mechanisms of action have been identified which include a pyridoxal phosphate dependent reaction and a non-pyridoxal phosphate dependent reaction. 

Biological Amines Are Products of Amino Acid Decarboxylation... 

Many important neurotransmitters are primary or secondary amines, derived from amino acids in simple pathways. In addition, some polyamines that form complexes with DNA are derived from the amino acid ornithine, a component of the urea cycle. A common denominator of many of these pathways is amino acid decarboxylation, another PLP-requiring reaction (see Fig. 18-6). 

Pyridoxal phosphate is a coenzyme in amino acid decarboxylations. What is a likely mechanism of the decarboxylation, and what are the products ... 

Amino acid decarboxylations are involved in the synthesis of several metabolically important amines, e.g., 5-hydroxytryptamine (serotonin) from tryptophan, histamine from histidine, and y-aminohutyric acid (GABA) from glutamate. 

The result of this path of ion formation is equivalent to the amine formation by amino acid decarboxylation. 

C. In the synthesis of each of these compounds, a decarboxylation of an amino acid occurs. Amino acid decarboxylation reactions, as well as transaminations, require pyridoxal phosphate. 

The role of a pyridinium-4-aldehyde in enzyme-catalysed amino acid decarboxylation 32.2.3 Riboflavin (Vitamin B2)... 

Amines are very toxic if ingested in great quantities, and their toxic effect is increased in the presence of alcohol. For this reason it is very important to perform the determination of amines in wine. The main amines, which are products of amino acid decarboxylation processes, are trypta mine, tyramine, and ethanolamine. The wine matrix is complex and requires a separation step in the sampling process, for which HPLC assures the best reliability. The sampling process also requires an extraction step before the separation step. 

Thiamine pyrophosphate (TPP) is the coenzyme required by enzymes that catalyze the transfer of a two-carbon fragment. Biotin is the coenzyme required by enzymes that catalyze carboxylation of a carbon adjacent to a carbonyl group. Pyridoxal phosphate (PLP) is the coenzyme required by enzymes that catalyze certain transformations of amino acids decarboxylation, transamination, racemiza-tion, C —Cp bond cleavage, and a,j8-elimination. In a transimination reaction, one imine is converted into another imine in a transamination reaction, the amino group is removed from a substrate and transferred to another molecule. 

Heme is synthesized from glycine and succinyl CoA (Fig. 44.3), which condense in the initial reaction to form 8-aminolevulinic acid (8-ALA) (Fig 44.4). The enzyme that catalyzes this reaction, 8-ALA synthase, requires the participation of pyridoxal phosphate, as the reaction is an amino acid decarboxylation reaction (glycine is decarboxylated see Chapter 39). 

OH free radicals do not react with the peptidic bond, but they may withdraw an H atom to the a-carbon. In the absence of oxygen, the fate of this free radical is not well known. In amino-acids, decarboxylation occurs (37), thus it might end up with protein fragmentation. In the presence of oxygen, a peroxyl radical is... 

Many bioactive amines arise by PLP-assisted amino acid decarboxylation. Decarboxylation of histidine, for example, gives histamine, a powerful vasodilator normally present in the body but formed in excessive amounts under conditions of traumatic shock. 

In addition to amino acid decarboxylation and racemization, PLP is a coenzyme for transamination— the transfer of an amino group from one compound to another. The enzymes that catalyze transaminations are called aminotransferases or transaminases. Many transaminations involve two compounds a-ketoglutaric acid and L-glutamic acid. 

In all reactions, the first stage is formation of SchifTs base a by condensation of PalP and the amino acid. Schiff s bases a and b represent part of transamination, but for the complete mechanism see Transamination. Racemization a- b, followed by b-ia-iamino acid-1-PalP, with addition of the proton in the opposite configuration. Amino acid decarboxylation a -> d- c - amine + PalP. Serine hydroxymethyltransferase (EC 2.1.2.1) X = OH L-serine + PalP a f- g glycine + PalP reversal of these reactions leads to L-serine synthesis from glycine the hydroxymethyl group is carried by te-trahydrofolic acid. Cysteine desulfhydrase (EC 4.4.1.1) X = SH cy eine + PalP a b-> c-y hydro-... 

Pyridoxal phosphate is a necessary coenzyme for a number of different biochemical reactions transamination, amino acid oxidation, amino acid decarboxylation, glycogen breakdown, and racemization of d- and L-amino acids. 

Pyridoxal phosphate is a necessary coenzyme for many amino acid decarboxylations. In these reactions, the carboxyl group adjacent to the a-amino group is split from the amino acid molecule. The detailed molecular mechanism of the reaction is not known, but studies with glutamic decarboxylase obtained from Escherichia coli have shed light on that mechanism. Ultracentrifugation and electrophoretic examination of the purified enzyme indicated that it has been obtained 90% pure and that the molecular weight was... 

Analysis of pyridoxal phosphate demonstrated that the enzyme contained 2 moles of the coenzyme per mole of apoenzyme. Spectroanalysis of the holoenzyme suggested that the formyl group of the pyridoxal phosphate forms imine bonds with the amino groups of the apoenzyme, and that when glutamate is added, a Schiff base is formed. In mammalian tissues, metabolites of considerable biological significance are formed by amino acid decarboxylation. Only a few of these reactions are presented here more detailed descriptions appear in other chapters [100]. 

The small molecules that assist in the catalytic processes enzymes promote and that are not themselves proteins are called coenzymes. Again, it will be recalled that these molecules are used to help consummate the reactions between substrates. So, for example, the coenzyme pyridoxal (vitamin Bg, Table 12.2) can (among other functions already discussed in Chapter 11) be utilized by a transaminase enzyme to help move a nitrogen from an amino acid (via initial reaction at an active-site lysine in the active site of the enzyme) to the a-carbonyl of an a-ketocarboxylic acid and vice versa (the process is called transamination). The pyridoxal (Table 12.2) has served as a catalytic nitrogen carrier. In some cases where pyridoxal (vitamin Bg) is used as a coenzyme, it is altered in the process. Thus, for example, in amino acid decarboxylation, pyridoxamine (HC=0 replaced by H2CNH2) can result and an additional step is required to reconvert it to pyridoxal. Indeed, such changes are common among coenzymes. 

Perry, H. M., Jr., Teitlebaum, S. and Schwartz, P. L., Effects of antihypertensive agents on amino-acid decarboxylation and amine oxidation, Fed. Proc. 14, 113 (1955). 

Fig. 31. Reactions of amino acid decarboxylation continued on opposite page).

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