Biomedical subjects

G M Hatch

Publications and source records attributed to G M Hatch.

59 records · Page 4Linked to original sources

PubMed1988

Effect of amino acids on choline uptake and phosphatidylcholine biosynthesis in the isolated hamster heart.

Choline uptake by the hamster heart has been shown to be enhanced by exogenous glycine. In this study, the effect of neutral, basic, and acidic amino acids on choline uptake was assessed. Hamster hearts were perfused with labelled choline, and in the presence of L-alanine, L-serine, or L-phenylalanine (greater than or equal to 0.1 mM), choline uptake was enhanced 20-38%. L-Arginine, L-lysine, L-aspartate, and L-glutamate did not influence choline uptake. The rate of phosphatidylcholine biosynthesis was unaffected by all amino acids tested. Enhancement of choline uptake by neutral amino acids was not additive or dose dependent but required a concentration threshold. The enhancement of choline uptake by neutral amino acids was not influenced by preperfusion with the same amino acid. Exogenous choline had no effect on the uptake of amino acids. We postulate that choline and the neutral amino acids are not cotransported and modulation of choline uptake is facilitated by direct interaction of the neutral amino acids with the choline transport system.

Amino Acids↗

PubMed1987

Phosphocholine phosphatase and alkaline phosphatase are different enzymes in hamster heart.

The CDP-choline pathway is the major pathway for the synthesis of phosphatidylcholine in the hamster heart. The formation of phosphocholine from choline was regarded as the first committed reaction in this pathway. We demonstrated earlier that the phosphocholine pool in the heart was substantially less than that found in other tissues, and we observed that a substantial amount of the phosphocholine was hydrolyzed back to choline by a phosphatase. This phosphatase was located in the microsomal fraction of the heart, and unlike alkaline phosphatase, it was not inhibited by amino acids. The pH optima and heat sensitivity of phosphocholine phosphatase were also found to differ from alkaline phosphatase. Phosphocholine did not inhibit the hydrolysis of p-nitrophenylphosphate, but a "mixed type" inhibition of the hydrolysis of phosphocholine was observed in the presence of p-nitrophenylphosphate. Our data support the hypothesis that these two activities originate from separate and distinct enzymes, and we postulate that the cardiac phosphocholine phosphatase may play a role in the regulation of the phosphocholine pool size in the hamster heart.

Alanine↗

PubMed1986

Enhancement of choline uptake by glycine in hamster heart.

Choline uptake by the isolated hamster heart has been shown to be inhibited by exogenous ethanolamine. In this study, the effect of glycine on choline uptake was investigated. At 0.01-1.0 mM glycine in the perfusate, an enhancement of choline uptake (30%) by the isolated heart was observed. Despite the higher choline uptake, the presence of glycine did not affect the rate of phosphatidylcholine biosynthesis. At higher glycine concentration (50 mM), the enhancement of choline uptake was abolished. Exogenous choline had no effect on the uptake of glycine. We postulate that choline and glycine are transported by separate mechanisms, and that glycine may play a regulatory role in the control of choline uptake by the hamster heart.

Animals↗

PubMedDate not supplied

Regulation of phosphatidylcholine metabolism in mammalian hearts.

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.

Animals↗

PubMedDate not supplied

Oleate stimulation of incorporation of exogenous glycerol into cardiolipin in isolated perfused rat heart does not involve direct activation of the CDP-DG pathway.

Oleate has been shown previously to stimulate the in vitro activity of phosphatidylglycerol-phosphatase, an important enzyme in the cytidine-5'-diphosphate-1,2-diacyl-sn-glycerol pathway of phosphatidylglycerol and cardiolipin biosynthesis. In this study the in vivo effect of oleate on the biosynthesis of new phosphatidylglycerol and cardiolipin was investigated in the heart. Hearts were perfused for 60 min with Krebs-Henseleit buffer containing [1,3-3H]glycerol and 0.6 mM albumin in the absence or presence of 0.6 or 1.2 mM oleate. Total incorporation of radioactivity was higher in the oleate-treated hearts compared with controls and this was due to an exclusive incorporation of radioactive glycerol into the organic phase. Also, the radioactivity incorporated into phosphatidylglycerol and cardiolipin was higher in the oleate-treated hearts compared with controls; however, the increase was greater in hearts perfused with 0.6 mM oleate compared with 1.2 mM oleate, indicating that pathophysiological concentrations of oleate may attenuate the oleate-induced stimulation of glycerol incorporation into polyglycerophospholipids. The pool size of phosphatidylglycerol and cardiolipin were unchanged in oleate-perfused hearts compared with controls. To investigate if the biosynthesis of phosphatidylglycerol and cardiolipin via the cytidine-5'-diphosphate-1,2-diacyl-sn-glycerol pathway was authentically stimulated by oleate hearts were pulse labeled for 15 min with 0.1 mM [1,3-3H]glycerol and subsequently chased for 60 min with 0.1 mM glycerol in the absence or presence of 0.6 mM oleate in the perfusate. Radioactivity incorporated into phosphatidylglycerol and cardiolipin was unchanged compared with controls. Our data indicate that oleate increases the incorporation of exogenous glycerol into polyglycerophospholipids but not accelerate synthesis from prelabeled precursor pools. Accordingly, oleate does not appear to stimulate directly enzymes of the cytidine-5'-diphosphate-1,2-diacyl-sn-glycerol pathway in vivo.

Animals↗