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F Davidoff

Publications and source records attributed to F Davidoff.

32 records · Page 2Linked to original sources
PubMed1972

Calcium-like action of phenethylbiguanide and related compounds: inhibition of pyruvate kinase.

Pyruvate kinase (EC 2.7.1.40) is inhibited by phenethylbiguanide. The kinetics of inhibition are competitive between biguanide and divalent, but not monovalent, metal cation activators of the enzyme; biguanide inhibition thus resembles inhibition by Ca(++). Alteration of either the polar or nonpolar portion of the phenethylbiguanide molecule quantitatively reduces its effectiveness as an inhibitor of pyruvate kinase, but the kinetics of inhibition remain qualitatively unchanged. Measurements of [(3)H]phenethylbiguanide binding to the enzyme indicate the presence of a single class of about 12 binding sites per enzyme molecule; binding characteristics are not significantly different in the presence of either monovalent or divalent metal cations. Studies with (45)Ca(++) and (54)Mn(++) demonstrate about 4 metal binding sites per enzyme molecule; phenethylbiguanide displaces these metal cations from the enzyme. Studies with several enzymes, dependent upon divalent metal cations, of both metal-bridge and substrate-bridge classes fail to show significant inhibition except at much higher phenethylbiguanide concentrations.

Animals↗
PubMed1968

Effects of guanidine derivatives on mitochondrial function. I. Phenethylbiguanide inhibition of respiration in mitochondria from guinea pig and rat tissues.

Derivatives of guanidine, such as phenethylbiguanide, are potent inhibitors of mitochondrial respiration in vitro, but the relevance of this inhibition to their in vivo blood sugar-lowering action is not clear. We have studied the metabolism of pyruvate and long chain fatty acids by mitochondria from several tissues of guinea pigs and rats and observed the effects of phenethylbiguanide on these processes. The rate of pyruvate decarboxylation and of beta-oxidation of long chain fatty acyl-CoA derivatives by guinea pig heart mitochondria in vitro has been found to exceed the flux of substrate through the citric acid cycle, both in the presence and absence of phosphate acceptor. When serum albumin is included in the incubation medium, the respiration of guinea pig heart, skeletal muscle, and liver mitochondria is inhibited by concentrations of phenethylbiguanide which approximate the levels achieved in those tissues in vivo. In the absence of albumin, the mitochondria are several fold less sensitive to phenethylbiguanide inhibition. Mitochondria from rat tissues are less sensitive than those of guinea pig to in vitro inhibition by phenethylbiguanide, but serum albumin alters sensitivity to inhibition in similar fashion in both species. During the breakdown of pyruvate or long chain fatty acyl-CoA, phenethylbiguanide demonstrates no specificity of inhibition toward the oxidative reactions before the citric acid cycle versus those of the cycle itself. However, oxidation of free fatty acids is relatively resistant to inhibition.

Adenine Nucleotides↗
PubMed1968

Effects of guanidine derivatives on mitochondrial function. II. Reversal of guanidine-derivative inhibiton by free fatty acids.

Long chain free fatty acids interfere with the inhibitory action of phenethylbiguanide and related compounds on mitochondrial respiration in vitro. This interference depends on binding of fatty acids to mitochondria and diminishes with decreasing chain length. Reversal of guanidine-derivative inhibition by fatty acids differs from that caused by dinitrophenol in that the effect of fatty acid is achieved without alteration in coupling or respiratory control. The binding of phenethylbiguanide to mitochondria is inhibited by both fatty acid and dinitrophenol. Serum albumin potentiates the inhibitory potency of guanidine derivatives, probably by removing endogenous mitochondrial free fatty acids.

Animals↗