Increased accumulation of fatty acids and their derivatives can impair insulin-stimulated glucose disposal by skeletal muscle. To characterize the nature of the defects in lipid metabolism and to evaluate the effects of thiazolidinedione treatment, we analyzed the levels of triacylglycerol, long-chain fatty acyl-coA, malonyl-CoA, fatty acid oxidation, AMP-activated protein kinase (AMPK), acetyl...

The protein substrates of sirtuin 5-regulated lysine malonylation (Kmal) remain unknown, hindering its functional analysis. In this study, we carried out proteomic screening, which identified 4042 Kmal sites on 1426 proteins in mouse liver and 4943 Kmal sites on 1822 proteins in human fibroblasts. Increased malonyl-CoA levels in malonyl-CoA decarboxylase (MCD)-deficient cells induces Kmal level...

Acute increases in the concentration of malonyl CoA play a pivotal role in mediating the decrease in fatty acid oxidation that occurs in many tissues during refeeding after a fast. In this study, we assess whether such increases in malonyl CoA in liver could be mediated by malonyl CoA decarboxylase (MCD), as well as acetyl CoA carboxylase (ACC). In addition, we examine how changes in the activi...

that cardiac decompensation can be avoided in MCD-deficient patients. Finally, by analogy with fatty acid oxidation disorders such as medium-chain acyl-CoA dehydrogenase deficiency (13), one may conclude that knowledge of the diagnosis will improve outcome because early intervention is then possible in catabolic episodes that otherwise may lead to metabolic derange-ment. It therefore seems reas...

Pseudomonas putida is able to grow on malonate as a sole source of carbon and energy. Malonate decarboxylase is a key enzyme catabolizing malonate to acetate and CO2. The enzyme consists of the five different subunits, (60 kDa), (33 kDa), (28 kDa), (13 kDa), and (30 kDa). The smallest subunit is an acyl-carrier protein (ACP) possessing 2'-(5"-phosphoribosyl)-3'-dephospho-CoA as a prosthetic gro...

Acute increases in the concentration of malonyl-CoA play a pivotal role in mediating the decrease in fatty acid oxidation that occurs in many tissues during refeeding after a fast. In this study, we assess whether such increases in malonyl-CoA in liver could be mediated by malonyl-CoA decarboxylase (MCD), as well as acetyl-CoA carboxylase (ACC). In addition, we examine how changes in the activi...

We report here a new mode of ATP synthesis in living cells. The anaerobic bacterium Propionigenium modestum gains its total energy for growth from the conversion of succinate to propionate according to: succinate + H(2)O --> propionate + HCO(3) ( big up tri, openG' = -20.6 kJ/mol). The small free energy change of this reaction does not allow a substrate-linked phosphorylation mechanism, and no ...

The study was designed to evaluate whether changes in malonyl-CoA and the enzymes that govern its concentration occur in human muscle as a result of physical training. Healthy, middle-aged subjects were studied before and after a 12-wk training program that significantly increased VO2 max by 13% and decreased intra-abdominal fat by 17%. Significant decreases (25-30%) in the concentration of mal...

An unexpected biochemical strategy for chain initiation is described for the loading module of the polyketide synthase of curacin A, an anticancer lead derived from the marine cyanobacterium Lyngbya majuscula. A central GCN5-related N-acetyltransferase (GNAT) domain bears bifunctional decarboxylase/S-acetyltransferase activity, both unprecedented for the GNAT superfamily. A CurA loading tridoma...

Malonyl-CoA decarboxylase (MCD), which catalyzes the conversion of malonyl-CoA to acetyl-CoA, is an evolutionarily distinct and highly conserved enzyme. MCD does not share sequence homology with other known decarboxylases, while the enzymes from different species exhibit at least >30% sequence identity to each other. In order to provide a canonical structure of the enzyme for detailed study of ...