Importance of the γ-Carboxyl Group of Glutamate-462 of the Large α-Subunit for the Catalytic Function and the Stability of the Multienzyme Complex of Fatty Acid Oxidation fromEscherichia coli†

Biochemistry ◽  
1997 ◽  
Vol 36 (1) ◽  
pp. 261-268 ◽  
Author(s):  
Xue-Ying He ◽  
Huinan Deng ◽  
Song-Yu Yang
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Carboxyl Group ◽  
Multienzyme Complex ◽  
Α Subunit ◽  
Fromescherichia Coli ◽  
Catalytic Function ◽  
The Stability

scholarly journals Control of mitochondrial gene expression in the aging rat myocardium

2006 ◽  
Vol 84 (2) ◽  
pp. 191-198 ◽  
Author(s):  
Christophe M.R LeMoine ◽  
Grant B McClelland ◽  
Carrie N Lyons ◽  
Odile Mathieu-Costello ◽  
Christopher D Moyes
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Transcriptional Regulators ◽  
Acid Oxidation ◽  
Mitochondrial Enzymes ◽  
Mrna Levels ◽  
Α Subunit ◽  
Transcript Levels ◽  
Nuclear Respiratory Factor ◽  
Age Dependent

Aging induces complex changes in myocardium bioenergetic and contractile properties. Using F344BNF1rats, we examined age-dependent changes in myocardial bioenergetic enzymes (catalytic activities and transcript levels) and mRNA levels of putative transcriptional regulators of bioenergetic genes. Very old rats (35 months) showed a 22% increase in ventricular mass with no changes in DNA or RNA per gram. Age-dependent cardiac hypertrophy was accompanied by complex changes in mitochondrial enzymes. Enzymes of the Krebs cycle and electron transport system remained within 15% of the values measured in adult heart, significant decreases occurring in citrate synthase (10%) and aconitase (15%). Transcripts for these enzymes were largely unaffected by aging, although mRNA levels of putative transcriptional regulators of the enzymes (nuclear respiratory factor (NRF) 1 and 2 α subunit) increased by about 30%–50%. In contrast, enzymes of fatty acid oxidation exhibited a more diverse pattern, with a 50% decrease in β-hydroxyacyl-CoA dehydrogenase (HOAD) and no change in long-chain acyl-CoA dehydrogenase or carnitine palmitoyltransferase. Transcript levels for fatty acid oxidizing enzymes covaried with HOAD, which declined significantly by 30%. There were no significant changes in the relative transcript levels of regulators of genes for fatty acid oxidizing enzymes: peroxisome proliferator-activated receptor-α (PPARα), PPARβ, or PPARγ coactivator-1α (PGC-1α). There were no changes in the mRNA levels of Sirt1, a histone-modifying enzyme that interacts with PGC-1α. Collectively, these data suggest that aging causes complex changes in the enzymes of myocardial energy metabolism, triggered in part by NRF-independent pathways as well as post-transcriptional regulation.Key words: PGC-1a, fatty acid oxidation, nuclear respiratory factor (NRF), PPAR, coactivator, transcriptional regulation.

scholarly journals Acetylation of Mitochondrial Trifunctional Protein α-Subunit Enhances Its Stability To Promote Fatty Acid Oxidation and Is Decreased in Nonalcoholic Fatty Liver Disease

2016 ◽  
Vol 36 (20) ◽  
pp. 2553-2567 ◽  
Author(s):  
Liang Guo ◽  
Shui-Rong Zhou ◽  
Xiang-Bo Wei ◽  
Yuan Liu ◽  
Xin-Xia Chang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Acid Oxidation ◽  
Fatty Liver Disease ◽  
Acid Oxidation ◽  
Α Subunit ◽  
Nonalcoholic Fatty Liver ◽  
Mitochondrial Trifunctional Protein

Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease, and decreased fatty acid oxidation is one of the important contributors to NAFLD. Mitochondrial trifunctional protein α-subunit (MTPα) functions as a critical enzyme for fatty acid β-oxidation, but whether dysregulation of MTPα is pathogenically connected to NAFLD is poorly understood. We show that MTPα is acetylated at lysine residues 350, 383, and 406 (MTPα-3K), which promotes its protein stability by antagonizing its ubiquitylation on the same three lysines (MTPα-3K) and blocking its subsequent degradation. Sirtuin 4 (SIRT4) has been identified as the deacetylase, deacetylating and destabilizing MTPα. Replacement of MTPα-3K with either MTPα-3KR or MTPα-3KQ inhibits cellular lipid accumulation both in free fatty acid (FFA)-treated alpha mouse liver 12 (AML12) cells and primary hepatocytes and in the livers of high-fat/high-sucrose (HF/HS) diet-fed mice. Moreover, knockdown of SIRT4 could phenocopy the effects of MTPα-3K mutant expression in mouse livers, and MTPα-3K mutants more efficiently attenuate SIRT4-mediated hepatic steatosis in HF/HS diet-fed mice. Importantly, acetylation of both MTPα and MTPα-3K is decreased while SIRT4 is increased in the livers of mice and humans with NAFLD. Our study reveals a novel mechanism of MTPα regulation by acetylation and ubiquitylation and a direct functional link of this regulation to NAFLD.

Specificity of carnitine action on fatty acid oxidation by heart muscle

1962 ◽  
Vol 202 (1) ◽  
pp. 117-121 ◽  
Author(s):  
Irving B. Fritz ◽  
Eli Kaplan ◽  
Kenneth T. N. Yue
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Heart Muscle ◽  
Hydroxyl Group ◽  
Acid Oxidation ◽  
Carboxyl Group ◽  
Amino Group ◽  
Long Chain Fatty Acids ◽  
Optimal Conditions ◽  
Long Chain

Carnitine (ß-hydroxy, γ-trimethylammonium butyrate), at concentrations of 10–5 m and more, increased the oxidation of long-chain fatty acids severalfold by heart muscle particulates incubated under optimal conditions. CoA dependency could be demonstrated in the presence of carnitine but not in its absence. Of a variety of compounds tested for carnitinelike activity, only acetylcarnitine and ß-hydroxy, γ-dimethylaminobutyrate ("norcarnitine") influenced palmitate oxidation in the assay system. Activity was abolished by removal of the hydroxyl group on the ß carbon; by replacement of the carboxyl group with either a cyano, an alcohol, or an amide grouping; or by substitution of an amino group for the trimethylammonium moiety of the molecule. Nonspecifically tritium-labeled carnitine was not degraded by heart particulates during incubation, indicating that carnitine acted catalytically to enhance fatty acid oxidation. The physiological significance of the data was discussed.

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