Histidine degradation

Kaminskas E, Y Kimhi, B Maganasik (1970) Urocanase and V-formrmino-L-glutamate formrminohy-drolase of Bacillus subtilis, two enzymes of the histidine degradation pathway. J Biol Chem 245 3536-3544. 

Figure 23.24. Histidine Degradation. Conversion of histidine into glutamate.

A third naturally occurring hydantoin, L-5-carboxyethylhydantoin, was first isolated by Brown and Kies127 from the urine of rats, monkeys and humans after being fed 14C-histidine, and it was postulated to be a by-product in the histidine degradation pathway shown in Fig. 12.4-6. Akamatsu1231 proved, by induction experiments, that the i-carboxyethylhydantoinase from a Bacillus brevis strain, also described by... 

Figure 12.4-6. Histidine degradation pathway and carboxyethylhydantoinase-catalyzed reaction.

The main pathway of L-histidine degradation includes formation of urocanic acid and leads to glutamic acid (Fig. 241). Histidine ammonia-lyase (like phenylalanine ammonia-lyase, D 22.2.1) catalyzes the transelimination of the NH2-group and a jff-hydrogen atom. Of minor importance in L-histidine degradation is the formation and further degradation of imidazole pyruvic acid. 

Degradation. One pathway of degradation is started by decarboxylation to histamine by the enzyme previously discussed. This is a minor pathway in terms of quantities of histidine metabolized. The major pathway in both animals and microorganisms retains the 5-carbon chain and leads to glutamic acid. Older work established that histidine degradation occurs only in the livers of animals, but this work was carried out only with crude preparations, and led to the publication and general acceptance of hypothetical schemes that have little relation to reactions found more recently. 

The bistaimne pathway of histidine degradation is of great interest because of the profound physiological importance of histamine. Histamine is bound in the mast cells in which it is formed. Released or administered histamine is rapidly oxidized to imidazoleacetaldehyde by... 

Brief reference will be made to the following papers which have appeared since this chapter was written. Partially purified Neurospora L-serine dehydrase has been studied. Both L-serine and L-threonine appear to be deaminated by the same enzyme. The enzymatic pathway of histidine degradation in liver has been investigated. Soluble gluta-minase I has been prepared. Additional eiddence for the Avide scope of transamination has appeared. The presence of an ornithine-a-keto-glutarate transaminase in neurospora has been demonstrated. Transamination of non-a-amino acids has been demonstrated in brain in... 

A new procedure for the determination of urocanic acid has been developed, based on the fact that this compound exhibits a strong absorption in the ultraviolet in the region of 240-280 m/i. This can be employed both to demonstrate the formation of urocanic acid and as a method of assay for the enzyme deaminating histidine to urocanic acid. With this test method it has been shown that urocanic acid accumulates when histidine is incubated with liver extract or with extracts of acetone-dried liver powder. Mehler and Tabor determined that the activity of the enzyme forming urocanic acid appeared to be sufficient to account for the total histidine degradation of liver extracts, as judged by the rate of formation of urocanic acid. 

The histamine pathway of histidine degradation includes a number of branches, involving methylation and nucleotide formation (Mehler, 1960). A major fraction of histamine is oxidized by mammals to imidazole-... 

A base, formed by the bacterial degradation of histidine, and present in ergot and in many animal tissues, where it is liberated in response to injury and to antigen-antibody reactions. If injected it causes a condition of shock with dilatation of many blood vessels, loss of plasma from the capillaries to the tissues and a rapid fall in blood pressure. It is normally prepared from protein degradation products. 

The first step in the biological degradation of histidine is formation of a 4-methylideneimidazol-5-one (MIO) by cyclization of a segment of the peptide chain in the histidine ammonia lyase enzyme. Propose a mechanism. 

Importantly, both incretins when secreted by the intestine are rapidly degraded by the dipeptidyl peptidase IV (DPPFV), which removed the two amino-terminus histidine-alanine residues, thereby, inactivating the incretins. This enzyme is present at the surface of the epithelial intestinal cells and capillaries in the vicinity of the K and L cells secreting GIP and GLP-1, respectively. It is also present in the... 

Figure 6.1 Histamine synthesis and metabolism in neurons. L-histidine is transported into neurons by the L-amino acid transporter. Once inside the neuron, L-histidine is converted into histamine by the specific enzyme histidine decarboxylase. Subsequently, histamine is taken up into vesicles by the vesicular monoamine transporter and stored there until released. In the absence of a high-affinity uptake mechanism in the brain, released histamine is rapidly degraded by histamine methyltransferase, which is located postsynaptically and in glia, to telemethylhistamine, a metabolite that does not show any histamine-like activity.

Valine, leucine, and isoleucine biosynthesis Lysine biosynthesis Lysine degradation Arginine and proline metabolism Histidine metabolism Tyrosine metabolism Phenylalanine metabolism Tryptophan metabolism Phenylalanine, tyrosine, and tryptophan biosynthesis Urea cycle and metabolism of amino groups... 

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