Effect of hypoxia on phosphatidylcholine biosynthesis in the isolated hamster heart.

Abstract

In hamster heart, the majority of the phosphatidylcholine is synthesized via the CDP-choline pathway, and the rate-limiting step of this pathway is catalysed by CTP:phosphocholine cytidylyltransferase (EC 2.7.7.15). We have shown previously [Choy (1982) J. Biol. Chem. 257, 10928-10933] that, in the myopathic heart, the level of cardiac CTP was diminished during the development of the disease. In order to maintain the level of CDP-choline, and consequently the rate of phosphatidylcholine biosynthesis, cardiac cytidylyltransferase activity was increased. However, it was not clear if the same compensatory mechanism would occur when the cardiac CTP level was decreased rapidly. In this study, hypoxia of the hamster heart was produced by perfusion with buffer saturated with 95% N2. The heart was pulse-labelled with radioactive choline and then chased with non-radioactive choline for various periods under hypoxic conditions. There was a severe decrease in ATP and CTP levels within 60 min of hypoxic perfusion, with a corresponding fall in the rate of phosphatidylcholine biosynthesis. Analysis of the choline-containing metabolites revealed that the lowered ATP level did not affect the phosphorylation of choline to phosphocholine, but the lower CTP level resulted in the decreased conversion of phosphocholine to CDP-choline. Determination of enzyme activities revealed that hypoxic treatment resulted in the enhanced translocation of cytidylyltransferase from the cytosolic to the microsomal form. This enhanced translocation was probably caused by the accumulation of fatty acids in the heart during hypoxia. We postulate that the enhancement of translocation of the cytidylyltransferase to the microsomal form (a more active form) is a mechanism by which the heart can compensate for the decrease in CTP level during hypoxia in order to maintain phosphatidylcholine biosynthesis.

• Authors: G M Hatch, P C Choy
• Journal: The Biochemical journal (Biochem J) Vol. 268 Issue 1 Pg. 47-54 (May 15 1990) ISSN: 0264-6021 [Print] England
• PMID: 2160812 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fatty Acids
• Phosphatidylcholines
• Phospholipids
• Cytidine Diphosphate Choline
• Cytidine Triphosphate
• Adenosine Triphosphate
• Nucleotidyltransferases
• Choline-Phosphate Cytidylyltransferase

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Choline-Phosphate Cytidylyltransferase
• Cricetinae
• Cytidine Diphosphate Choline (metabolism)
• Cytidine Triphosphate (metabolism)
• Cytosol (enzymology)
• Fatty Acids (metabolism)
• Hypoxia (metabolism)
• Kinetics
• Myocardium (metabolism)
• Nucleotidyltransferases (metabolism)
• Phosphatidylcholines (biosynthesis)
• Phospholipids (metabolism)