Inhibition of rabbit muscle isozymes by vitamin C.
The ability of vitamins C, E and K to inhibit enzymes directly has been investigated. It was found that vitamin E and some analogs and menadione (vitamin K3) inhibited several enzymes irreversibility at concentrations below one millimolar. Ascorbate inhibits rabbit muscle 6-phosphofructokinase (MPFK-1; EC 2.7.1.11), muscle type LDH (EC 1.1.1.27), and muscle AK (EC 2.7.4.3) at low concentrations that do not inhibit equivalent liver isozymes. Ascorbate Ki values for muscle-type LDH and heart-type LDH isozymes are 0.007 and 3 mM, respectively. The ascorbate Ki value for rabbit skeletal muscle PFK-1 is 0.16 mM; liver PFK-I is not inhibited by ascorbate. Dehydroascorbate does not inhibit any enzyme at ascorbate concentrations normally found in cells. All ascorbate inhibitions are completely reactivated or nearly so by L-ascorbate oxidase, CYS, GSH, or DTT. We propose a hypothesis that ascorbate facilitates glycogen storage in muscle by inhibiting glycolysis. The relationship between ascorbate metabolism and diabetes is discussed.
Russell
P J
PJ
Department of Biology, University of California, San Diego, La Jolla 92093-0690, USA.
Williams
A
A
Austin
T A
TA
D000263:Adenylate Kinase / Q000037:antagonists & inhibitors*; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D003683:Dehydroascorbic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors*; D008099:Liver / Q000201:enzymology; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000201:enzymology*; D010084:Oxidation-Reduction; D010732:Phosphofructokinase-1 / Q000037:antagonists & inhibitors*; D011817:Rabbits; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology; D014812:Vitamin K / Q000494:pharmacology
D004791:Enzyme Inhibitors; D013438:Sulfhydryl Compounds; D014812:Vitamin K; D014810:Vitamin E; D007770:L-Lactate Dehydrogenase; D010732:Phosphofructokinase-1; D000263:Adenylate Kinase; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid