P1, P5-Bis-(5'-adenosyl)pentaphosphate: is this adenylate kinase inhibitor substrate for mitochondrial processes?
1. P1, P5-Bis-(5'-adenosyl) pentaphosphate (AP5-A) inhibits "soluble" adenylate kinase even when this enzyme is an integral part of the complete mitochondrion. The Ki is 10(-5) M, i.e. about two orders of magnitude higher than the inhibitor contants determined for the purified adenylate kinase of rabbit muscle and an enzyme preparation separated from the mitochondrial intermembrane space. The weaker inhibitory effect is due to a lower accessibility of the enzyme. 2. as to be expected Ap5A which is of the "multisubstrate analogue"-type does not affect mitochondrial nucleoside diphosphate kinase. 3. Though Ap5A owns the structural elements of both ATP and ADP it is not a substrate of the adenine nucleotide carrier, i.e. neither it is exchanged across the inner mitochondrial membrane nor speicifically bound. 4. Ap5A is not metabolized by rat liver mitochondria.
D000227:Adenine Nucleotides; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000263:Adenylate Kinase / Q000037:antagonists & inhibitors*; D000818:Animals; D001278:Atractyloside / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D002417:Cattle; D004072:Digitonin; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology*; D009701:Nucleoside-Diphosphate Kinase / Q000378:metabolism; D009841:Oligonucleotides; D010101:Oxygen Consumption; D010770:Phosphotransferases / Q000037:antagonists & inhibitors*; D051381:Rats
D000227:Adenine Nucleotides; D002352:Carrier Proteins; D009841:Oligonucleotides; D001278:Atractyloside; D000255:Adenosine Triphosphate; D010770:Phosphotransferases; D000263:Adenylate Kinase; D009701:Nucleoside-Diphosphate Kinase; D004072:Digitonin