Elsevier

Molecular Aspects of Medicine

Volume 25, Issues 5–6, October–December 2004, Pages 495-520
Molecular Aspects of Medicine

Review
Carnitine palmitoyltransferases 1 and 2: biochemical, molecular and medical aspects

https://doi.org/10.1016/j.mam.2004.06.004Get rights and content

Abstract

Carnitine palmitoyltransferase (CPT) deficiencies are common disorders of mitochondrial fatty acid oxidation. The CPT system is made up of two separate proteins located in the outer (CPT1) and inner (CPT2) mitochondrial membranes. While CPT2 is an ubiquitous protein, three tissue-specific CPT1 isoforms––the so-called “liver” (CPT1-A), “muscle” (CPT1B) and «brain» (CPT1-C) CPT1s––have been shown to exist. Amino acid and cDNA nucleotide sequences have been identified for all of these proteins. CPT1-A deficiency presents as recurrent attacks of fasting hypoketotic hypoglycemia. Twenty four CPT1A mutations have been reported to date. CPT1-B and -C deficiencies have not been hitherto identified. CPT2 deficiency has several clinical presentations. The “benign” adult form (more than 200 families reported) is characterized by episodes of rhabdomyolysis triggered by prolonged exercise. The prevalent S113L mutation is found in about 50% of mutant alleles. The infantile-type CPT2 presents as severe attacks of hypoketotic hypoglycemia, occasionally associated with cardiac damage commonly responsible for sudden death before 1 year of age. In addition to these symptoms, features of brain and kidney dysorganogenesis are frequently seen in the neonatal-onset CPT2 deficiency, almost always lethal during the first month of life. Around 40 CPT2 mutations (private missense or truncating mutations) have hitherto been detected. Treatment is based upon avoidance of fasting and/or exercise, a low fat diet enriched with medium chain triglycerides and carnitine. Prenatal diagnosis may be offered for pregnancies at a 1/4 risk of infantile/severe-type CPT2 deficiency.

Section snippets

CPT-system

Transport of LCFA from cytosol into the mitochondrial matrix of mammalian cells via β-oxidation requires a special protein association, the carnitine palmitoyltransferase system that reversibly catalyzes the following reaction:palmitoyl-CoA+carnitinepalmitoylcarnitine+CoA-SH

Since 1963 (Fritz et al., 1963), it has generally been accepted that at least two functionally separate forms of CPT existed: an “outer” CPT1 which catalyzes the formation of acylcarnitine from carnitine and acyl-CoA, and

Liver-type CPT1 (CPT1-A) deficiency

In the small number of cases reported to date, the affected enzyme is clearly the “liver” isoform. Since the first report in 1981 (Bougneres et al., 1981), over 20 families have been reported (Demaugre et al., 1988; Tein et al., 1989; Bonnefont et al., 1989; Vianey-Saban et al., 1993; Gray et al., 1991; Stanley et al., 1992; Haworth et al., 1992; Falik-Borenstein et al., 1992; Yamamoto et al., 1994; Bergman et al., 1994; Schaefer et al., 1997; Innes et al., 1997; Ijlst et al., 1998; Olpin et

Acknowledgements

The support of l'Association Française contre les Myopathies is gratefully acknowledged.

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