System substrate specificity

The substrate specificity of ACE is low. ACE cleaves a variety of pairs of amino acids from the carboxy-terminal part of several peptide substrates. The conversion of ANGI to ANGII and the degradation of bradykinin to inactive fragments are considered the most important functions of ACE. Both peptides have profound impact on the cardiovascular system and beyond. ACE is thus an important target for ACE inhibitors. These compounds are frequently and efficiently used in the treatment of hypertension and cardiac failure. 

VMAT1 is expressed in the adrenal medulla, by small intensely fluorescent cells in sympathetic ganglia, and by other nonneural cells that release monoamines. In contrast, VMAT2 is expressed by neuronal populations in the nervous system. The substrate specificity for the two isoforms is similar, but VMAT2 has a somewhat higher apparent affinity for all monoamines than VMAT1. In addition, only VMAT2 appears able to transport histamine, consistent with its expression by mast cells. 

Although the absolute configurations of the products are opposite to that of antiinflammatory active compounds, and the substrate specificity is rather restricted as to the steric bulkiness around the reaction center, the enzyme system of A. bronchisepticus was proved to have a unique reactivity. Thus, detailed studies on the isolated enzyme were expected to elucidate some new interesting mechanism of the new type of decarboxylation. Thus, the enzyme was purified. (The enzyme is now registered as EC 4.1.1.76.) The molecular mass was about 24kDa. The enzyme was named as arylmalonate decarboxylase (AMDase), as the rate of the decarboxylation of phenylmalonic acid was faster than that of the a-methyl derivative. ... 

Cytochrome P450-type monooxygenase systems, which have a generally low substrate specificity, are widely distributed in the species of fish used for toxicity testing (Funari et al. 1987). 

Parales RE, MD Emig, NA Lynch, DT Gibson (1998) Substrate specificities of hybrid naphthalene and 2,4-dinitrotioluene dioxygenase enzyme systems. J Bacteriol 180 2337-2344. 

The methanotroph Methylosinus trichosporium strain OB3b that produces the soluble MMO system consisting of a 40 kDa NADH oxidoreductase, a 245 kDa hydroxylase, and a 16 kDa protein termed component B has a low substrate specificity (Sullivan et al. 1998). 

The 3-ketothiolase has been purified and investigated from several poly(3HB)-synthesizing bacteria including Azotobacter beijerinckii [10], Ral-stonia eutropha [11], Zoogloea ramigera [12], Rhodococcus ruber [13], and Methylobacterium rhodesianum [14]. In R. eutropha the 3-ketothiolase occurs in two different forms, called A and B, which have different substrate specificities [11,15]. In the thiolytic reaction, enzyme A is only active with C4 and C5 3-ketoacyl-CoA whereas the substrate spectrum of enzyme B is much broader, since it is active with C4 to C10 substrates [11]. Enzyme A seems to be the main biosynthetic enzyme acting in the poly(3HB) synthesis pathway, while enzyme B should rather have a catabolic function in fatty-acid metabolism. However, in vitro studies with reconstituted purified enzyme systems have demonstrated that enzyme B can also contribute to poly(3HB) synthesis [15]. 

Meier, P. J., et al. Substrate specificity of sinusoidal bile acid and organic anion uptake systems in rat and human liver. Hepatology 1997, 26, 1667-1677. 

This was in contrast to the enzymatic reactions known then, where enzymes were believed to be very substrate specific. As we now know, there is no general catalytic system to perform asymmetric hydrogenations and even within a small class of substrates, some ligand variation is required to achieve optimal results. 

The enzyme system catalyzing the reactions of Eqs. (21) and (22) has not yet been sufficiently purified for studying its substrate specificity. However, a number of aldoses and aldehydes serving as substrates in reaction (21) have been described (H4). 

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