Mammals substrate specificity

Mammals, fungi, and higher plants produce a family of proteolytic enzymes known as aspartic proteases. These enzymes are active at acidic (or sometimes neutral) pH, and each possesses two aspartic acid residues at the active site. Aspartic proteases carry out a variety of functions (Table 16.3), including digestion pepsin and ehymosin), lysosomal protein degradation eathepsin D and E), and regulation of blood pressure renin is an aspartic protease involved in the production of an otensin, a hormone that stimulates smooth muscle contraction and reduces excretion of salts and fluid). The aspartic proteases display a variety of substrate specificities, but normally they are most active in the cleavage of peptide bonds between two hydrophobic amino acid residues. The preferred substrates of pepsin, for example, contain aromatic residues on both sides of the peptide bond to be cleaved. 

The classical role of AChEs is to terminate transmission of neuronal impulses by rapid hydrolysis of ACh. The closely related butyrylcholin-esterases (BuChEs) or pseudocholinesterases have a less stringent substrate specificity but their function remains ill-defined. In mammals, BuChE is found at high concentration in the plasma and the gut, where it has been... 

According to biochemical separation, location, and substrate specificity, epoxide hydrolases (EH) have been divided into a number of groups. In mammals, the insoluble microsomal epoxide hydrolases and the soluble cytosolic epoxide hydrolases are enzymes of broad and complementary substrate specificity. 

Since numerous DUBs are present in eukaryotic organisms (Table 2), it is probable that they possess substrate specificity. UCHs have been studied in some detail with respect to their substrate specificity. Two major UCHs in mammals are UCH-Ll and UCH-L3. Larsen et al showed that UCH-Ll cleaves linear polyubiquitin molecules more efficiently than UCH-L3. In contrast, UCH-L3 appears to prefer ubiquitin fused to small ribosomal proteins (see Figure 7). The tissue distribution of the two UCHs is indicative of their functional specialization as well. UCH-Ll is a neuronal-specific enzyme whereas UCH-L3 is expressed primarily in hematopoietic tissues. Another UCH called UCH-L2 has wide tissue distribution. ... 

In mammals, at least four groups of Ser/Tlir phosphatases can be differentiated the members of these groups are known as protein phosphatases (PP) 1, 2A, 2B and 2C. PP-1, PP-2A and PP-2B are highly homologous with respect to the sequence of the catalytic domain but they differ in substrate specificity and type of regulation. 

Figure 1 Fatty acid synthesis in mammals. Gene encoding enzymes are shown in italics and are based on current evidence for substrate specificities. (A) De novo fatty acid synthesis. (B) Synthesis of the highly unsaturated fatty acids AA, EPA, and DHA from Cl 8 2 oo3 and Cl 8 3 m3 obtained from the diet. Details are found within the text.

NAA, or lAA ( ). In vitro studies with enzymes from mammals suggest that xenobiotic carboxylic acids are activated by a reaction that requires ATP and CoA. The xenobiotic acyl-CoA derivative is then released from the enzyme surface. The initial activation reactions are catalyzed by different acyl-CoA synthetase enzymes with different substrate specificities. Benzoic and phenylacetlc acid derivatives are activated by what appears to be a butyrl-CoA synthetase present in the mitochondrial matrix. The final reaction is catalyzed by an acyl-CoA amlno acid N-acyltransferase. Two closely related forms have been purified from bovine liver mitochondria. 

Class I aldolases of mammals and other vertebrates can be subdivided into three distinct isoenzymes.143,331 Identification of the parental aldolases A, B, and C has been made from their substrate specificities (ratio of activity towards D-fructose 1,6-bisphosphate and towards D-fructose 1-phosphate), electrophoretic mobilities, tissue distribution, and specific immunological properties. Aldolase A is the major form, present in muscle aldolase B, the predominant form in liver and kidney and aldolase C, present in brain with aldolase A. In tissues where more than one aldolase isoenzyme occurs, a hybrid form is often observed.331... 

MGL catalyzes the o ,7-elimination reaction of methionine to a-ketobutyrate, methanethiol, and ammonia. MGL has been isolated from a number of bacteria, including Pseudomonas putida, Aeromonas sp., Clostridium sporogenes, P. taetrolens, and Brevibacterium linens, from the primitive protozoa Entamoeba histolytica and Trichomonas vaginalis, but is not believed to be present in yeast, plants, or mammals. " " Two MGL isoforms have been isolated from T. vaginali and Entamoeba histolytica, which differ in substrate specificity, overall charge, and catalytic properties. They show a high degree of sequence identity to MGL from Pseudomonas putida. MGL has demonstrated antitumor efficacy in a number of methionine-dependent cancer cell lines. ... 

The sEH enzyme catalyzes the hydrolysis of various epoxides to their corresponding diols. Homologues of sEH have been identified in almost all organisms, including bacteria, fungi, plants, insects, and mammals. The human sEH is an interesting enzyme that possesses two different active sites, one for epoxide hydrolysis and one for phosphate ester hydrolysis." " In humans, sEH is mainly found in the liver, where it converts various xenobiotic epoxides into their corresponding vicinal diols. sEH exhibits a broad substrate specificity but seems to prefer rntw-substituted epoxides. ... 

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