fatty acid beta-oxidation
Saturday 19 July 2003
Definition: Acyl-CoA dehydrogenases (ACADs; EC 18.104.22.168) are mitochondrial enzymes that catalyze the initial rate-limiting step in the beta-oxidation of fatty acyl-CoA. ACAD9 belongs to a group of ACADs that act on fatty acids containing 14 to 20 carbons.
Mitochondrial fatty acid beta-oxidation
Mitochondrial fatty acid beta-oxidation is one of the main energy-producing metabolic pathways in eukaryotes through the entry of acetyl-CoA into the Krebs cycle.
Fatty acids are oxidized inside the mitochondrial matrix but the fatty acids to be oxidized come from the cytosol.
Fatty acids are activated in the cytosol by esterification with Coenzyme A (CoA) to form acyl-CoA (RCO-CoA, where R is the fatty acid acyl group).
Activated medium-chain fatty acids (C8 fatty acid and C10 fatty acid) freely diffuse into mitochondria to be oxidized but long chain fatty acids do not diffuse into mitochondria so they must be transported in.
The transport of long chain fatty acids into mitochondria for oxidation is accomplished by the carnitine palmitoyltransferase system (CPTI and CPTII).
CPTI exchanges carnitine for the CoA attached to long chain fatty acids to form a fatty acid-carnitine conjugate (RCO-carnitine).
The fatty acid-carnitine is transported into the matrix by a transporter protein in the inner mitochondrial membrane. Once the fatty acid-carnitine is inside the matrix, CPTII exchanges CoA for carnitine to produce fatty acid-CoA once again, ready to enter fatty acid oxidation in the matrix to produce energy.
The free carnitine is transported back out to renew the cytoplasmic pool of carnitine and allow the transfer process to continue. (From Biocarta)
Acyl-CoA dehydrogenases (ACADs) (EC 22.214.171.124) are mitochondrial enzymes that catalyze the initial rate-limiting step in the beta-oxidation of fatty acyl-CoA.
fatty acid beta oxidation
fatty acid omega oxidation
Fatty acid oxidation disorders
SCHAD deficiency (MIM.231530)
MCAD deficiency (medium-chain acyl-CoA dehydrogenase deficiency) (MIM.201450)
LCHAD deficiency (long-chain acyl-CoA dehydrogenase deficiency) (MIM.600890)
VLCAD deficiency (very long-chain acyl-CoA dehydrogenase deficiency) (MIM.609575)
ACAD9 deficiency (MIM.611103) (17564966)
- neonatal sudden death
- sudden deat in infancy
- cardiomyocytic steatosis
- acute cardiac failure
- cardiac arrythmias
- conduction anomalies
- Reye syndrome
- true hepatic failure (LCHAD)
retinitis pigmentosa (LCHAD)
peripheral neuropathy (LCHAD)
plasma acylcarnitine profile
urinary organic acid profile
total and free plasma carnitine
long-chain fatty acid loading test
in vitro studies of fatty acid oxidation on fresh lymphocytes or cultured fibroblasts
avoiding fasting or catabolism
long-term dietary therapy
- prevent periods of fasting
- restrict long-chain fatty acid intake with supplementation of medium-chain triglycerides
mitochondrial fatty acid oxydation
fatty acid oxidation diseases
He M, Rutledge SL, Kelly DR, Palmer CA, Murdoch G, Majumder N, Nicholls RD, Pei Z, Watkins PA, Vockley J. A new genetic disorder in mitochondrial fatty acid beta-oxidation: ACAD9 deficiency. Am J Hum Genet. 2007 Jul;81(1):87-103. PMID: 17564966
Oey NA, DEN Boer ME, Wijburg FA, Vekemans M, Auge J, Steiner C, Wanders RJ, Waterham HR, Ruiter JP, Attie-Bitach T. Long-Chain Fatty Acid Oxidation during Early Human Development. Pediatr Res. 2005 Apr 21; PMID: 15845636
Saudubray JM, Martin D, de Lonlay P, Touati G, Poggi-Travert F, Bonnet D, Jouvet P, Boutron M, Slama A, Vianey-Saban C, Bonnefont JP, Rabier D, Kamoun P, Brivet M. Recognition and management of fatty acid oxidation defects: a series of 107 patients. J Inherit Metab Dis. 1999 Jun;22(4):488-502. PMID: 10407781
Bennett MJ, Powell S. Metabolic disease and sudden, unexpected death in infancy. Hum Pathol. 1994 Aug;25(8):742-6. PMID: 8056419