Arginine enzymes, table

Quite unexpectedly, EDRF was found to be the gas nitric oxide (NO). NO is formed by the action of the enzyme NO synthase, which is cytosolic. The endothe-hal and neuronal forms of NO synthase are activated by Ca + (Table 49-8). The substrate is arginine, and the products are citmUine and NO ... 

In view of the toxicity of ammonia, complete absence of any one of the enzymes of the cycle is fatal. Nonetheless, disorders of the cycle do occur, which are caused by a low activity of one of the enzymes or carbamoyl phosphate synthetase. In addition, defects in N-acetylglutamate synthase have been reported, but they are very rare. With the exception of ornithine transcarbamoylase, the deficiencies have an autosomal recessive mode of inheritance. The transcarbamoylase deficiency is inherited as an X-linked dominant trait, usually lethal in male patients. A deficiency of carbamoyl phosphate synthetase, ornithine transcarbamoylase or argininosuccinate synthetase results in accumulation and excretion of citrulline. A deficiency of argininosuccinate lyase results in the accumulation and excretion of argininosuccinate and arginine (Table 10.5). The abbreviations CPSD, OTCD, ASD, ALD and AD stand, respectively, for the deficiencies of these enzymes, where D stands for deficiency. 

So far nine arginine methyltransferases [46] and more than 20 lysine methyltransferases [11] have been identified in humans. Many of them show links to cancer. We discuss several of these subtypes below and an overview can be found in Tables 12.1 and 12.2. For lysine methyltransferases traditionally individual names have been used for the various subtypes. Lately, a common nomenclature for chromatin modifying enzymes has been proposed. For the human lysine methyltransferases the name KMTs should be used in analogy to (P)RMTs and eight groups (KMTl-8) with different subtypes suggested for some members [47]. But this nomenclature is not used consistently even throughout the recent literature so we provide both names if available in Table 12.2. 

A substrate L-benzoyl arginine /)-nitroanilide hydrochloride was hydrolyzed by trypsin, with inhibitor concentrations of 0, 0.3, and 0.6 mmol 1 T The hydrolysis rates obtained are listed in Table 3.3 [5]. Determine the inhibition mechanism and the kinetic parameters (A", and /Cj) of this enzyme... 

The amino acid composition of the /3-lactamases listed in Table III (2, 40, 41, 43, 45, 54, 55, 58, 62-64) underlines the similarities between preparations derived from closely related strains of bacteria, especially if the combined basic and acidic amino acid content is compared (23). The staphylococcal enzymes are remarkably rich in lysine, and the lysine-arginine content of the other gram-positive /3-lactamases is almost as high. Complete absence of cysteine appears to be characteristic (2, 55), although j3-lactamases which contain at least one cysteine residue have been reported (37, 65, 66). 

In Table II are shown the results from kinetic studies with commercially available gastric and pancreatic enzymes. Trypsin was strongly inhibited, at least at a low concentration of casein as substrate. The hydrolysis of benzoyl arginine ethyl ester (BAEE) by trypsin was non-competitively inhibited, giving a 30% reduction of Vmax at 0.5 mg/ml of the LMW fraction. Carboxypepti-dase A, and to a lesser extent carboxypeptidase B, were non-competitively inhibited as well. Pepsin and chymotrypsin were not affected by the conditions used in these assays. 

In agreement with the enzyme s specificity, acidic amino acids and N-alkylated amino acids afforded poor inhibitors. The discovery that lysine in the penultimate position provided good inhibition was at the time unprecedented in the ACE substrate or snake venom peptide literature, and this development was pursued with additional analogues (Table VI). Excellent activity was obtained with arginine and with higher and lower homologues of lysine. Even the s-N-acetyllysine analogue 33 (Table VI) was active. 

The amino acids with a second amino group are important because of their basicity and they are vital to the catalytic activity of many enzymes. Histidine has a p/Qh very close to neutrality (6.5) and can function as an acid or a base. Lysine and arginine are much more basic, but are normally proto-nated in living things. An extra column in this table gives the pfCgH of the extra amino groups. 

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