A synthesis of acylphosphonic acids and of 1-aminoalkylphosphonic acids: the action of pyruvate dehydrogenase and lactate dehydrogenase on acetylphosphonic acid.
Acylphosphonic acids, R-CO-PO(OH)2, have been synthesized by the steps [formula: see text] of which the last is new and provides a mild method for de-esterifying acylphosphonic acids. Their reductive amination gives a simple way of making 1-aminoalkylphosphonic acids. Acetylphosphonic acid inhibited NAD+ reduction by pyruvate with the pyruvate dehydrogenases from Escherichia coli and Bacillus stearothermophilus. The inhibition was competitive with pyruvate, with Ki of 6 microM for the E. coli enzyme (pyruvate Km 0.5 mM) and one of 0.4 mM of the B. stearothermophilus enzyme (pyruvate Km 0.1 mM). Acetylphosphonate and its monomethyl ester are substates for pig heart lactate dehydrogenase, with Km values of 15 mM and 10 mM respectively (pyruvate Km 0.05 mM) and specificity constants one thousandth that for pyruvate.
Dixon
H B
HB
Department of Biochemistry, University of Cambridge, U.K.
Giddens
R A
RA
Harrison
R A
RA
Henderson
C E
CE
Norris
W E
WE
Parker
D M
DM
Perham
R N
RN
Slater
P
P
Sparkes
M J
MJ
D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000378:metabolism; D000215:Acylation; D000478:Alkylation; D000818:Animals; D001667:Binding, Competitive; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology; D001411:Geobacillus stearothermophilus / Q000201:enzymology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000494:pharmacology*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism / Q000494:pharmacology*; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D013329:Structure-Activity Relationship; D013552:Swine
D004791:Enzyme Inhibitors; D063065:Organophosphonates; D011768:Pyruvate Dehydrogenase Complex; D011773:Pyruvates; C003126:phosphonoacetaldehyde; D019289:Pyruvic Acid; D007770:L-Lactate Dehydrogenase; D000079:Acetaldehyde