Sandbox 212
From Proteopedia
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Carnitine palmitoyltransferase (CPTs) have long chain fatty acids substrate preference and are found in the outer mitochondrial | Carnitine palmitoyltransferase (CPTs) have long chain fatty acids substrate preference and are found in the outer mitochondrial | ||
membrane and the mitochondrial matrix. | membrane and the mitochondrial matrix. | ||
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| + | * '''The role of carnitine acyltransferases in fatty acid oxidation''' | ||
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| + | The most important biological function of carnitine acyltransferases is the transport of fatty acids for β-oxidation.CPT-I and CPT-II are crucial for the β-oxidation of long chain fatty acids in the mitochondria, by facilitating their transport across the mitochondrial membrane. | ||
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[[Image:Second step.jpg|thumb|second step of the carnitine shuttle|600px|right]] | [[Image:Second step.jpg|thumb|second step of the carnitine shuttle|600px|right]] | ||
Revision as of 13:41, 23 December 2011
Carnitine acyltransferases are a large family of enzymes that play a main role in cellular energy metabolism, i.e. fatty acid oxidation. These enzymes catalyze the reversible exchange of acyl groups between coenzyme A and carnitine. Carnitine acyltransferases include three different classes of enzymes which are known as carnitine acetyltransferases (CrATs), carnitine octanoyltransferases (CrOTs) and carnitine palmityltransferase (CPTs). The three classes differ in their acyl group specificity as well as their localization. [1] In this article we will focus on the structure of carnitine acetyltransferase as a representitive of carnitine acyltransferases. Determining the structure and thus the molecular basis for fatty acid transfer is needed for drug development.Being major enzymes in fatty acid oxidation carnitine acyltransferases are viewed as promising targets which can be used to develop successful therapeutics against type 2 diabetes, obesity and other human diseases.
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Biological function
- Differences within carnitine acyltransferase family members
All members of carnitine acyltransferases catalyze the same reversible reaction:the exchange of acyl groups between carnitine and coenzyme A (CoA)--> see picture. This is in accord with the fact, that the catalytic domains of all the carnitine acyltransferases are well conserved. However the three known classes of carnitine acyltransferases differ in their acyl group specificity, subcellular localization, tissue distribution, and physiological function(3). Carnitine acetyltransferase (CrATs) prefere short chain fatty acids as substrates and are localized in the mitochondrial matrix, the endoplasmic reticulum, and the peroxisome. Carnitine octanoyltransferases (COTs) show medium chain fatty acid substrate preference and are mainly found in peroxisomes. Carnitine palmitoyltransferase (CPTs) have long chain fatty acids substrate preference and are found in the outer mitochondrial membrane and the mitochondrial matrix.
- The role of carnitine acyltransferases in fatty acid oxidation
The most important biological function of carnitine acyltransferases is the transport of fatty acids for β-oxidation.CPT-I and CPT-II are crucial for the β-oxidation of long chain fatty acids in the mitochondria, by facilitating their transport across the mitochondrial membrane.
Overall structure of Carnitine acetyltransferase
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The tertiary structure of CAT consists of 20 α-helices (α1-α20) and 16 β-strands (named β1-β16) which are arranged into two equally sized domains (N and C domains ).
