The effect of amino acids, monoamines and polyamines on pyruvate dehydrogenase activity in mitochondria from rat adipocytes.
The ability of polyamines and other cationic compounds including monoamines, amino acids, poly-L-arginine, poly-D-lysine and poly-L-lysine, to alter pyruvate dehydrogenase (PDH) activity in mitochondria from rat epididymal adipocytes was determined. PDH was assayed with the substrate [1-14C] pyruvate in the presence of 0.05 mM Ca2+ and Mg2+. Nine of the fourteen compounds tested at 0.1 mM caused a significant increase (procaine, 3-(beta-morpholinopropionyl) benzo [b]thiophene [VII], spermine, spermidine, putrescine, lysine and tryptophan) or decrease (poly-L-arginine, 3-(beta-piperidinopropionyl) benzo[b]thiophene) in PDH activity. None of these compounds nonenzymatically decarboxylated [1-14C] pyruvate to release 14CO2. NaF, a PDH phosphatase inhibitor, suppressed the stimulatory effects of those compounds tested: procaine, tryptophan, VII, spermine and spermidine. These results imply that these five compounds activate PDH activity through stimulation of the PDH phosphatase. When the Mg2+ concentration was increased from 0.05 to 4.5 mM, the stimulatory effect of spermine was increased, consistent with the finding by others that spermine lowers the Km of the enzyme for Mg2+. However, at Mg2+ concentrations greater than 0.3 mM, the stimulatory effect of VII was unaltered, procaine failed to alter PDH activity, lysine inhibited PDH activity, and poly-L-lysine stimulated PDH activity. Therefore, polyamines and other positively charged small molecules may be physiologic regulators of PDH activity.
Kiechle
F L
FL
Department of Clinical Pathology, William Beaumont Hospital, Royal Oak, MI 48072.
Malinski
H
H
Dandurand
D M
DM
McGill
J B
JB
D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D000588:Amines / Q000494:pharmacology*; D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D011073:Polyamines / Q000494:pharmacology*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012969:Sodium Fluoride / Q000494:pharmacology
D000588:Amines; D000596:Amino Acids; D011073:Polyamines; D011768:Pyruvate Dehydrogenase Complex; D012969:Sodium Fluoride; D008274:Magnesium; D002118:Calcium