Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.6.5.3 (
complex I
)
8,901
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The reaction catalyzed by succinate-CoA ligase in the mitochondrial matrix yields a high-energy phosphate when operating towards hydrolysis of the thioester bond of succinyl-CoA, known as mitochondrial substrate-level phosphorylation (mSLP). The catabolism of several metabolites converge to succinyl-CoA but through different biochemical pathways. Among them, threonine, serine and methionine catabolize to succinyl-CoA through the common intermediate,
2-ketobutyrate
. During the course of this pathway
2-ketobutyrate
will become succinyl-CoA through propionyl-CoA catabolism, obligatorily passing through an ATP-consuming step substantiated by propionyl-CoA carboxylase. Here, by recording the directionality of the adenine nucleotide translocase while measuring membrane potential we tested the hypothesis that catabolism of
2-ketobutyrate
negates mSLP due to the ATP-consuming propionyl-CoA carboxylase step in rotenone-treated, isolated mouse liver and brain mitochondria. 2-
Ketobutyrate
produced a less negative membrane potential compared to NADH or FADH
2
-linked substrates, which was sensitive to inhibition by rotenone, atpenin and arsenate, implying the involvement of
complex I
, complex II and a dehydrogenase-most likely branched chain keto-acid dehydrogenase, respectively. Co-addition of
2-ketobutyrate
with NADH- or FADH
2
-linked substrates yielded no greater membrane potential than in the presence of substrates alone. However, in the presence of NADH-linked substrates,
2-ketobutyrate
prevented mSLP in a dose-dependent manner. Our results imply that despite that
2-ketobutyrate
leads to succinyl-CoA formation, obligatory metabolism through propionyl-CoA carboxylase associated with ATP expenditure abolishes mSLP. The provision of metabolites converging to
2-ketobutyrate
may be a useful way for manipulating mSLP without using pharmacological or genetic tools.
...
PMID:The Effect of 2-Ketobutyrate on Mitochondrial Substrate-Level Phosphorylation. 3081 Sep 78
