ACE enzyme

Thus, PUFAs, especially an optimal combination of ERA, DHA and possibly, GLA, DGLA, and AA, show all the qualities of the suggested polypiU, viz they show aspirin-like action, inhibit the activities of HMG-CoA and ACE enzymes, possess diuretic and antihypertensive actions, and indirectly show 6-blocker-like action. 

Neurokinin effects are terrninated by proteolysis. In vitro acetylcholinesterase (ACE) and enkephalinase can hydrolyze substance P. However, there appears to be no clear evidence that either acetylcholinesterase or ACE limit the actions of released substance P. Enkephalinase inhibitors, eg, thiorphan, can augment substance P release or action in some systems but the distribution of enkephalinase in the brain does not precisely mirror that of substance P. There appears to be a substance P-selective enzyme in brain and spinal cord. 

One of the homochiral starting materials (45) for the acetylcholinesterase (ACE) inhibitor captopril [62571 -86-2] (47) is produced by a Hpase enzyme-catalyzed resolution of racemic 3-methyl-4-acetylthiobutyric acid (44) and L-proline (46) (65). 

Thiazide diuretics have a venerable history as antihypertensive agents until the advent of the angiotensin-converting enzyme (ACE) inhibitors this class of drugs completely dominated first line therapy for hypertension. The size of thi.s market led until surprisingly recently to the syntheses of new sulfonamides related to the thiazides. Preparation of one of the last of these compounds starts by exhaustive reduction of the Diels-Alder adduct from cyclopentadiene and malei-mide (207). Nitrosation of the product (208), followed by reduction of the nitroso group of 209,... 

FIGURE 9.20 Design of multiple ligancl activity, (a) Dual histamine HI receptor and leukotriene receptor antagonist incorporating known antihistaminic properties of cyproheptadine and LTD4. (b) Joint ACE/NEP inhibitor formed from incorporating similarities in substrate structures for both enzymes. From [57],... 

Angiotensin converting enzyme (ACE) plays a central role in cardiovascular hemostasis. Its major function is the generation of angiotensin (ANG) II from ANGI and the degradation of bradykinin. Both peptides have profound impact on the cardiovascular system and beyond. ACE inhibitors are used to decrease blood pressure in hypertensive patients, to improve cardiac function, and to reduce work load of the heart in patients with cardiac failure. 

ACE inhibitors inhibit the degradation of bradykinin and potentiate the effects of bradykinin by about 50-100-fold. The prevention of bradykinin degradation by ACE inhibitors is particularly protective for the heart. Increased bradykinin levels prevent postischemic reperfusion arrhythmia, delays manifestations of cardiac ischemia, prevents platelet aggregation, and probably also reduces the degree of arteriosclerosis and the development of cardiac hypertrophy. The role of bradykinin and bradykinin-induced NO release for the improvement of cardiac functions by converting enzyme inhibitors has been demonstrated convincingly with use of a specific bradykinin receptor antagonist and inhibitors of NO-synthase. 

Most ACE inhibitors are prodrugs, with the exceptions of captopril, lisinopril, and ceranapril. Prodrugs exert improved oral bioavailability, but need to be converted to active compounds in the liver, kidney, and/or intestinal tract. In effect, converting enzyme inhibitors have quite different kinetic profiles with regard to half time, onset and duration of action, or tissue penetration. 

Hyperkalemia is an excess of potassium in the blood. Clinical symptoms are muscle weakness and cardiac arrhythmias. It is caused by, e.g., hyperaldosteronism and angiotensin-converting enzyme (ACE) inhibitors. 

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