Substitutions of three amino acids in human heart/muscle type carnitine palmitoyltransferase I caused by single nucleotide polymorphisms.
Heart/muscle type carnitine palmitoyltransferase I (M-CPTI) catalyzes the rate-limiting step of mitochondrial long-chain fatty acid (LCFA) oxidation in muscle and adipose tissue. Three replacements of nucleotides resulting in missense mutations of I66V, S427C, and E531K were observed in the M-CPTI gene of patients showing abnormal fatty acid metabolism. These nucleotide replacements were found to be common single nucleotide polymorphisms (SNPs) of this gene and not specific to patients. The question of whether these missense mutations caused by SNPs alter the functional properties of M-CPTI remains unanswered. Thus, we examined whether these missense mutations are associated with any changes in the enzymatic properties of M-CPTI. None of these mutations was found to cause remarkable alteration of its enzymatic properties. Based on the comparison of amino acid sequences of M-CPTI among different animal species, the roles of these amino acids in the enzyme are discussed.
Yamazaki
Naoshi
N
Faculty of Pharmaceutical Sciences, University of Tokushima, Shomachi-1, Tokushima, Japan. yamazaki@ph.tokushima-u.ac.jp
Matsuo
Taisuke
T
Kurata
Miho
M
Suzuki
Makiko
M
Fujiwaki
Takehisa
T
Yamaguchi
Seiji
S
Terada
Hiroshi
H
Shinohara
Yasuo
Y
D019943:Amino Acid Substitution; D000818:Animals; D019556:COS Cells; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics* / Q000378:metabolism; D002522:Chlorocebus aethiops; D005227:Fatty Acids / Q000235:genetics / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D008052:Lipid Metabolism, Inborn Errors / Q000235:genetics* / Q000378:metabolism; D008929:Mitochondria, Heart / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D009206:Myocardium / Q000201:enzymology; D010084:Oxidation-Reduction; D020641:Polymorphism, Single Nucleotide
D005227:Fatty Acids; D002334:Carnitine O-Palmitoyltransferase