Methylhistidines

Hydroxylated amino acids (eg, 4-hydroxyproline, 5-hydroxylysine) and A/-methylated amino acids (eg, /V-methylhistidine) are obtained by the acid hydrolysis of proteins. y-Carboxyglutamic acid occurs as a component of some sections of protein molecules it decarboxylates spontaneously to L-glutamate at low pH. These examples are formed upon the nontranslational modification of protein and are often called secondary protein amino acids... 

Decarboxylation of histidine to histamine is catalyzed by a broad-specificity aromatic L-amino acid decarboxylase that also catalyzes the decarboxylation of dopa, 5-hy-droxytryptophan, phenylalanine, tyrosine, and tryptophan. a-Methyl amino acids, which inhibit decarboxylase activity, find appfication as antihypertensive agents. Histidine compounds present in the human body include ergothioneine, carnosine, and dietary anserine (Figure 31-2). Urinary levels of 3-methylhistidine are unusually low in patients with Wilson s disease. 

The smdy of tissue protein breakdown in vivo is difficult, because amino acids released during intracellular breakdown of proteins can be extensively reutilized for protein synthesis within the cell, or the amino acids may be transported to other organs where they enter anabohc pathways. However, actin and myosin are methylated by a posttranslational reaction, forming d-methylliistidine. During intracellular breakdown of actin and myosin, 3-methylhistidine is released and excreted into the urine. The urinary output of the methylated amino acid provides a rehable index of the rate of myofibrillar protein breakdown in the musculature of human subjects. 

Excretion of creatinine, 3-methylhistidine and urea are low, indicating a low rate of protein degradation. 

Modified amino acids, which occur in special proteins such as hydroxyproline in collagen and 3-methylhistidine in actin and myosin, can be used as indicators of the degradation of these proteins. 

Dunnet, M. and Harris, R. C. (1997). High-performance liquid chromatographic determination of imidazole dipeptides, histidine, 1-methylhistidine and 3-methylhistidine in... 

Figure 14-11 Schematic diagram of the active site of the pyruvoyl enzyme histidine decarboxylase showing key polar interactions between the pyruvoyl group and groups of the inhibitor O-methylhistidine and surrounding enzyme groups. Aspartate 63 appears to form an ion pair with the imidazolium group of the substrate.268 Hydrogen bonds are indicated by dotted lines. See Gallagher et al.269...

Actin and the thin filaments. There are at least six forms of actin in adult mammalian tissues a-cardiac, a-skeletal muscle, a- and y-smooth muscle, P- and y-cytoplasmic.87 89 All of them are closely homologous, e.g., the 42-kDa a-skeletal muscle actin differs in only 4 of 375 residues from the a-cardiac form and only in 6 residues from the y-smooth form. In almost all organisms actins contain one residue of N5-methylhistidine at position 73.87/88/90 Actin is an unusual protein in that... 

Other products from histidine include the hormonal substance histamine formed by decarboxylation, the oxidation product, imidazole acetic acid, and N5- and A/c-methylhistidines. Histamine plays a role in release of gastric secretions and allergic responses (Chapter 5). Drugs (antihistamines) that inhibit its release are in widespread use. The unusual amino acid diphthamide has an unknown function in pro-... 

Soupart s data for histidine excretion are lower than those of Stein and of Evered because they do not include 3-methylhistidine. The data of Stein and Evered include 3-methylhistidine because their figures were obtained with Moore and Stein s 1951 method and not their 1954 method which was used by Soupart (S24). 

In some of these cases, the figures given for histidine may be slightly on the high side, since 3-methylhistidine (Tl) happens sometimes not to be completely separated from histidine (S22, S23). 

Histidine peak obtained on 100-cm column contains 3-methylhistidine. These results, although minimal owing to incomplete recovery of the basic amino acids in experiments of this type, involve an overestimation for histidine. 

These are to be considered as maximal values because of elevated blank reading in the range from the NH, peak to the 3-methylhistidine peak (Moore Stein, 1954, M15). For histidine, values obtained by an enzymic specific decarboxylation method are a little lower than those obtained on 150-cm column (Soupart, 1958, S23). 

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