Regulation of phosphatidylcholine metabolism in mammalian hearts

1989 ◽  
Vol 67 (2-3) ◽  
pp. 67-77 ◽  
Author(s):  
Grant M. Hatch ◽  
Karmin O ◽  
Patrick C. Choy
Keyword(s):  
Phospholipase A ◽  
Current Evidence ◽  
Major Phospholipid ◽  
Mammalian Heart ◽  
Ctp:Phosphocholine Cytidylyltransferase ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Phosphatidylcholine Biosynthesis ◽  
Rate Limiting ◽  
Phosphatidylcholine Metabolism

Phosphatidylcholine is the major phospholipid in the mammalian heart. Over 90% of the cardiac phosphatidylcholine is synthesized via the CDP-choline pathway. The rate-limiting step of this pathway is catalyzed by CTP:phosphocholine cytidylyltransferase. Current evidence suggests that phosphatidylcholine biosynthesis in the heart is regulated by the availability of CTP and the modulation of cytidylyltransferase activity. Phosphatidylcholine is degraded mainly by the actions of phospholipase A1 and A2, with the formation of lysophosphatidylcholine. Lysophosphatidylcholine may be further deacylated by lysophospholipase or reacylated back into the parent phospholipid by the action of acyltransferase. The accumulation of lysophosphatidylcholine in the heart may be one of the biochemical factors for the production of cardiac arrhythmias.Key words: phosphatidylcholine, phospholipids, biosynthesis, metabolism, heart.

Effect of cAMP on choline uptake and phosphatidylcholine biosynthesis in cultured chick heart cells

1988 ◽  
Vol 66 (3) ◽  
pp. 231-237 ◽  
Author(s):  
Paul S. Sunga ◽  
P. Haydn Pritchard ◽  
Simon W. Rabkin
Keyword(s):  
Phosphodiesterase Inhibitor ◽  
Cardiac Cells ◽  
Heart Cells ◽  
Choline Uptake ◽  
Ctp:Phosphocholine Cytidylyltransferase ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Phosphatidylcholine Biosynthesis ◽  
Chick Heart ◽  
Rate Limiting

The effect of an analogue of cAMP on the uptake and metabolism of choline in the heart was studied in isolated cardiac cells. The cells were obtained from 7-day-old chick embryos and maintained in culture. The effects of cAMP were studied using the dibutyryl cAMP analogue and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. After a 2-h incubation with [3H]choline, about 85% of the label was recovered in phosphocholine, with most of the rest in phospholipid. During a subsequent chase incubation, [3H]phosphocholine was transferred to phosphatidylcholine with little accumulation in CDP-choline. This suggests the rate-limiting step for the conversion of phosphocholine to phosphatidylcholine in these cells is the synthesis of CDP-choline. cAMP decreased the incorporation of choline into phosphatidylcholine, but did not change the flux of metabolites through the step catalyzed by CTP:phosphocholine cytidylyltransferase. cAMP had little effect on choline uptake at low (1–25 μM) extracellular choline concentrations, but significantly (p < 0.05) decreased choline uptake at higher (37.5–50 μM) extracellular choline concentrations. Thus, cardiac cells take up and metabolize choline to phosphocholine, with CTP:phosphocholine cytidylyltransferase being the rate-limiting step in phosphatidylcholine biosynthesis. cAMP decreases [3H]choline uptake and its subsequent incorporation into phosphocholine and phospholipid. However, the metabolism of choline within the cell is unaffected.

Choline glycerophospholipid biosynthesis in the guinea pig heart

1987 ◽  
Vol 65 (10) ◽  
pp. 860-868 ◽  
Author(s):  
Monika Wientzek ◽  
Ricky Y. K. Man ◽  
Patrick C. Choy
Keyword(s):  
Guinea Pig ◽  
Choline Kinase ◽  
Major Pathway ◽  
Guinea Pig Heart ◽  
Ctp:Phosphocholine Cytidylyltransferase ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Choline Glycerophospholipids ◽  
Mammalian Liver ◽  
Rate Limiting

The aims of this study were to (i) elucidate the biosynthetic pathways for the formation of plasmenylcholine in the mammalian heart and (ii) investigate whether the control of choline glycerophospholipid production is different in hearts with high plasmenylcholine content. Guinea pig hearts were used throughout this study, since 34% of the cardiac choline glycerophospholipids in this species is present in the plasmenylcholine form. By perfusion of the guinea pig heart in the Langendorff mode with labeled choline, we demonstrated that the majority of plasmenylcholine in the heart was synthesized via the CDP-choline pathway. The ability of the heart to form plasmenylcholine from CDP-choline and 1-alkenyl-2-acylglycerol was also shown. We postulate that 1-alkenyl-2-acylglycerol in the guinea pig heart might originate from the hydrolysis of plasmenylethanolamine. In mammalian liver and other tissues, the CDP-choline pathway is the major pathway for phosphatidylcholine biosynthesis and the rate-limiting step is catalyzed by CTP:phosphocholine cytidylyltransferase. The results obtained from the present study support this supposition. In addition, evidence was obtained indicating that phosphorylation of choline by choline kinase in the CDP-choline pathway may also be rate limiting. Although the involvement of choline kinase as a rate-limiting enzyme in the CDP-choline pathway has been shown in a number of cell cultures, the rate-limiting role of this enzyme in intact mammalian organs has not been previously reported. The rationale for the presence of more than one rate-limiting step in the CDP-choline pathway in the guinea pig heart remains undefined.

scholarly journals Effect of hypoxia on phosphatidylcholine biosynthesis in the isolated hamster heart

1990 ◽  
Vol 268 (1) ◽  
pp. 47-54 ◽  
Author(s):  
G M Hatch ◽  
P C Choy
Keyword(s):  
Active Form ◽  
Compensatory Mechanism ◽  
Ctp:Phosphocholine Cytidylyltransferase ◽  
Hypoxic Conditions ◽  
Rate Limiting Step ◽  
Phosphatidylcholine Biosynthesis ◽  
Hamster Heart ◽  
Rate Limiting ◽  
Hypoxic Treatment

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.

Ornithine Decarboxylase Activity in Cultured Endothelial Cells Stimulated by Serum, Thrombin and Serotonin

1978 ◽  
Vol 39 (02) ◽  
pp. 496-503 ◽  
Author(s):  
P A D’Amore ◽  
H B Hechtman ◽  
D Shepro
Keyword(s):  
Endothelial Cells ◽  
Ornithine Decarboxylase ◽  
Decarboxylase Activity ◽  
Aortic Endothelial Cells ◽  
Ornithine Decarboxylase Activity ◽  
Rate Limiting Step ◽  
Bovine Aortic Endothelial Cells ◽  
Limiting Step ◽  
Rate Limiting ◽  
Serum Serotonin

SummaryOrnithine decarboxylase (ODC) activity, the rate-limiting step in the synthesis of polyamines, can be demonstrated in cultured, bovine, aortic endothelial cells (EC). Serum, serotonin and thrombin produce a rise in ODC activity. The serotonin-induced ODC activity is significantly blocked by imipramine (10-5 M) or Lilly 11 0140 (10-6M). Preincubation of EC with these blockers together almost completely depresses the 5-HT-stimulated ODC activity. These observations suggest a manner by which platelets may maintain EC structural and metabolic soundness.

Dynamics of hepatic and peripheral insulin effects suggest common rate-limiting step in vivo

Diabetes ◽  
1993 ◽  
Vol 42 (2) ◽  
pp. 296-306 ◽  
Author(s):  
D. C. Bradley ◽  
R. A. Poulin ◽  
R. N. Bergman
Keyword(s):  
Rate Limiting Step ◽  
Limiting Step ◽  
Rate Limiting
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