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Inhibition of angiotensin converting enzyme (ACE) by normal solutes of human plasma
Author(s) -
Ryan James Walter
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1247-d
Subject(s) - chemistry , angiotensin converting enzyme , ornithine , arginine , sodium , kinetics , enzyme , endocrinology , medicine , biochemistry , amino acid , blood pressure , physics , organic chemistry , quantum mechanics
Human plasma ACE concentration is ~4 nM, yet net ACE activity is <1 nM. Inhibition is evident on assaying ACE of increasing dilutions of plasma. Here, means are defined for computing net ACE activity of undiluted plasma, total ACE and % inhibition. Under first order kinetics, the Michaelis‐Menten equation is v/s = V max /(K m (1 + i/K i )), where i is inhibitor concentration; v/s is called apparent (app) (V max /K m ). The inverted equation describes a straight line: app(K m /V max ) = K m /V max K i (i) + K m /V max . When i, fractional concentration (fr conc) of plasma, is plotted against app(K m /V max ), the y‐intercept is true (K m /V max ). The x‐intercept is the fr conc of plasma for inhibition of ACE by half. Net ACE activity of undiluted plasma is computed for i = 1.0; 1/x is units of inhibitory activity. Plasmas of 37 healthy adults, 23 – 57 y.o., were assayed in fr conc of 0.2 – 0.00625 using [ 3 H]hippuryl‐His‐Leu, 40 nM, in Hepes buffer, pH 8.0, plus NaCl and sodium sulfate, at 37 o C. Results (mean±SD): V max /K m 0.3755±0.098/min, app(V max /K m ) 0.0442±0.003/min, inhibitor units 7.29±2.0, inhibition 88.2±5.0%. Thus, <12% of plasma ACE is active. Inhibition, relieved by dialysis, is attributable to arginine, lysine, ornithine, cysteine, Cys‐Gly and glutathione. Following a meal, their concentrations can double and increase inhibition, which raises the question, Is ACE activity physiologically modulated by food intake?