Mitochondrial trifunctional protein deficiency: A severe fatty acid oxidation disorder with cardiac and neurologic involvement

2003 ◽  
Vol 142 (6) ◽  
pp. 684-689 ◽  
Author(s):  
Margarethe E.J. den Boer ◽  
Carlo Dionisi-Vici ◽  
Anupam Chakrapani ◽  
Anders O.J. van Thuijl ◽  
Ronald J.A. Wanders ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Protein Deficiency ◽  
Acid Oxidation ◽  
Fatty Acid Oxidation Disorder ◽  
Neurologic Involvement ◽  
Mitochondrial Trifunctional Protein

A Fetal Fatty-Acid Oxidation Disorder as a Cause of Liver Disease in Pregnant Women

1999 ◽  
Vol 54 (11) ◽  
pp. 679
Author(s):  
Jamal A. Ibdah ◽  
Michael J. Bennett ◽  
Piero Rinaldo ◽  
Yiwen Zhao ◽  
Beverly Gibson ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Pregnant Women ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Fatty Acid Oxidation Disorder

3-Hydroxydicarboxylic and 3-ketodicarboxylic aciduria in three patients: evidence for a new defect in fatty acid oxidation at the level of 3-ketoacyl-CoA thiolase

1993 ◽  
Vol 39 (5) ◽  
pp. 897-901 ◽  
Author(s):  
M J Bennett ◽  
W G Sherwood
Keyword(s):  
Mass Spectrometry ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Mass Spectra ◽  
Gas Chromatography Mass Spectrometry ◽  
Acid Oxidation ◽  
Fatty Acid Oxidation Disorder ◽  
Urinary Organic Acids ◽  
First Time ◽  
Long Chain

Abstract Three patients presented with evidence of a fatty acid oxidation disorder. Analysis of urinary organic acids by gas chromatography/mass spectrometry demonstrated the presence of medium-chain (C6-C12) dicarboxylic, 3-hydroxydicarboxylic, and 3-ketodicarboxylic acids in all three urines. 3-Ketodicarboxylic aciduria is reported for the first time here, as are the mass spectra for 3-ketosuberic, 3-ketosebacic, and 3-ketododecanedioic acids and the oximated spectrum for 3-ketoadipic acid. The presence of 3-ketodicarboxylic acids suggests a defect at the level of a long-chain 3-ketoacyl-CoA thiolase, an enzyme for which a deficiency state has not previously been described. Our patients may represent the first cases of a long-chain thiolase defect.

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.

scholarly journals Child Neurology: Recurrent rhabdomyolysis due to a fatty acid oxidation disorder

Neurology ◽  
2013 ◽  
Vol 82 (1) ◽  
pp. e1-e4 ◽  
Author(s):  
G. Terrone ◽  
M. Ruoppolo ◽  
N. Brunetti-Pierri ◽  
C. Cozzolino ◽  
E. Scolamiero ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Fatty Acid Oxidation Disorder ◽  
Child Neurology ◽  
Recurrent Rhabdomyolysis
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