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PMID: 8858564 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Regulation of cardiolipin biosynthesis in the heart.

Molecular and cellular biochemistry ·Vol. 159 ·No. 2 ·1996-06-21 ·Pages 139-48

Hatch GM

Abstract

Cardiolipin is one of the principle phospholipids in the mammalian heart comprising as much as 15-20% of the entire phospholipid phosphorus mass of that organ. Cardiolipin is localized primarily in the mitochondria and appears to be essential for the function of several enzymes of oxidative phosphorylation. Thus, cardiolipin is essential for production of energy for the heart to beat. Cardiac cardiolipin is synthesized via the cytidine-5'-diphosphate-1,2-diacyl-sn-glycerol pathway. The properties of the four enzymes of the cytidine-5'-diphosphate-1,2-diacyl-sn-glycerol pathway have been characterized in the heart. The rate-limiting step of this pathway is catalyzed by the phosphatidic acid: cytidine-5'-triphosphate cytidylyltransferase. Several regulatory mechanisms that govern cardiolipin biosynthesis in the heart have been uncovered. Current evidence suggests that cardiolipin biosynthesis is regulated by the energy status (adenosine-5'-triphosphate and cytidine-5'-triphosphate level) of the heart. Thyroid hormone and unsaturated fatty acids may regulate cardiolipin biosynthesis at the level of three key enzymes of the cytidine-5'-diphosphate-1,2-diacyl-sn-glycerol pathway, phosphatidylglycerol phosphate synthase, phosphatidyl-glycerolphosphate phosphatase and cardiolipin synthase. Newly synthesized phosphatidic acid and phosphatidylglycerol may be preferentially utilized for cardiolipin biosynthesis in the heart. In addition, separate pools of phosphatidylglycerol, including an exogenous (extra-mitochondrial) pool not derived from de novo phosphatidylglycerol biosynthesis, may be utilized for cardiac cardiolipin biosynthesis. In several mammalian tissues a significant number of studies on polyglycerophospholipid biosynthesis have been documented, including detailed studies in the lung and liver. However, in spite of the important role of cardiolipin in the maintenance of mitochondrial function and membrane integrity, studies on the control of cardiolipin biosynthesis in the mammalian heart have been largely neglected. The purpose of this review will be to briefly discuss cardiolipin and cardiolipin biosynthesis in some selected model systems and focus primarily on current studies involving the regulation of cardiolipin biosynthesis in the heart.

MeSH Terms
Animals Cardiolipins/biosynthesis Cytosine Nucleotides/metabolism Hormones/physiology Membrane Proteins Mitochondria, Heart/metabolism Myocardium/metabolism Nucleotidyltransferases/metabolism Phosphatidylglycerols/metabolism Phosphoric Monoester Hydrolases/metabolism Transferases (Other Substituted Phosphate Groups)/metabolism
Chemicals
Cardiolipins Cytosine Nucleotides Hormones Membrane Proteins Phosphatidylglycerols Nucleotidyltransferases phosphatidate cytidylyltransferase Transferases (Other Substituted Phosphate Groups) cardiolipin synthetase CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase Phosphoric Monoester Hydrolases phosphatidylglycerophosphatase
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Hatch G M
Department of Internal Medicine, University of Manitoba, Winnipeg, Canada.
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Article Info
Journal
Molecular and cellular biochemistry
Abbr.
Mol Cell Biochem
ISSN
0300-8177
DOI
10.1007/BF00420916
Published
1996-06-21
Pages
139-48
Language
English
Region
Netherlands
NLM ID
0364456
Subset
IM
External Links
PubMed source DOI: 10.1007/BF00420916 View journal details
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