Renin enzyme properties

A second peptide is pepsitensin, formed by peptic digestion of the substrate of renin (13). It represents an interesting type reaction similar to that of renin. Because two proteolytic enzymes, renin and pepsin, act on a protein to produce vasoconstrictor substances, the substrate must have peculiar structural properties conducive to formation of these substances when broken down. The pharmacology of pepsitensin has not been ex-... 

In recent years a number of potent peptidomimetic inhibitors of HIV-1 protease have been reported in the literature. One highly potent series was designed to be symmetric molecules to complement the enzyme [60] (Fig. 10). However, as with renin inhibitors, these analogs often carry with them the properties associated with peptides low cellular activity and poor oral bioavailability. The quest, therefore, for a nonpeptide inhibitor again became the focus of our efforts as well as that of numerous other laboratories. In contrast to the renin studies. 

Alzheimer s disease is characterized by plaques in the brain consisting primarily of the 40-42 amino acid amyloid / -peptide (A/ ) [258]. AfS derives from proteolysis of the amyloid precursor protein (APP) by the fS and y sec-retases to create the N and C-termini of the peptide respectively [259]. The / -secretase has recently been identified as a 501 amino-acid transmembrane protein by several research groups [260-263], The enzyme, variously named BACE, memapsin2, and Asp2, is an aspartic protease related to pepsin, cathepsin D, and renin, with all the properties expected of the /i-sccrctasc. 

The products of the phospho-aldol reaction, a-functionalised phosphonate esters such as a-hydroxy- and a-aminophosphonates, find widespread application directly or indirectly as precursors to enzyme inhibitors (such as the enzymes renin [6], thrombin [7],EPSP synthase [8], HIV protease [9] and various classes of PTK and PTPs [10]) and phosphate analogues [11], antibiotics [ 12], antiviral agents [ 13], and in nucleotide technology [ 14]. Within each application stereochemistry of the phosphonate is crucial to eliciting the required properties [15]. 

Proteins are digested in the stomach and intestine under the influence of proteolytic enzymes. The stomach contains at least two enzymes— pepsin and renin— which are secreted by the mucosal cells in the form of zymogens. The gastric cell secretes pepsinogen, a long polypeptide molecule with no catalytic property. Pepsin is activated to pepsinogen within the gastric lumen under the influence of at least two factors the low pH of the medium, which is a result of hydro-... 

A more recent approach to the treatment of hypertension with vasodilators is illustrated by captopril (Squibb, 1981). The body has several mechanisms for controlling blood pressure. One involves renin, an enzyme produced in the kidney, which cleaves a polypeptide to produce angiotensin I, a decapeptide. This in turn is cleaved by angiotensin converting enzyme to produce angiotensin II, an octapeptide which has potent vasoconstrictor properties. Captopril is an angiotensin-converting enzyme inhibitor and lowers blood... 

Both the REF and renin are kidney enzymes which act on a plasma protein substrate. However, their different chemical and physiologic properties militate against their being the same substance. Thus, renin is stable in acid solutions (pH 2.5), while the REF is inactivated at pH 5.0 Moreover, intraperitoneal administration to polycythemic assay mice of 3.7 Goldblatt units of purified renin, incubated for 60 minutes in saline or in diaHyzed serum, did not result in stimulation of erybhropoiesis (Fig. lO). 

Properties of these high-molecular-weight renins are summarized in Table VII. The fact that the pi of the big-big renin is clearly different from that of the other species eliminates the possibility that big-big renin is an oligomeric complex of the smaller species. The inverse relationship between the molecular weights and the specific activities of these renins strongly suggests the existence of an enzyme-precursor relationship as shown below ... 

The attempts to reproduce experimentally the syndrome essentially similar to hypertension led to the discovery of the renal hypertensin (226,585). Various stimuli, whether physiological or not, provoke the liberation from the renal cortex, of a protein called renin, which has been extracted (414) and partially purified (508). Renin is an enzyme which reacts with a pseudoglobulin in the serum, hypertensinogen, to produce a peptide, hypertensin or angiotonin, which has certain vasoconstrictive and hypertensive properties. In publications by Schales (509) and Corcoran (139), numerous details on renin and its characteristics are found, and Corcoran et al. (140) have recently studied hypertension. 

Renin shows the following properties, characteristic for an enzyme ) with fixed amounts of substrate the renin concentration determines the speed of hypertensin formation but not the final yield (22,117) (2) the maximal yield of hypertensin is proportional to the amount of substrate used (22,117) (3) renin shows a typical pH-activity curve (Fig. 1). Optimal activity is found between pH 7.5 and 8.5 (117). 

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