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H Jamil

Publications and source records attributed to H Jamil.

47 records · Page 3Linked to original sources

Head-group specificity for feedback regulation of CTP:phosphocholine cytidylyltransferase.

The specificity of the phospholipid head-group for feedback regulation of CTP: phosphocholine cytidylyltransferase was examined in rat hepatocytes. In choline-deficient cells there is a 2-fold increase in binding of cytidylyltransferase to cellular membranes, compared with choline-supplemented cells. Supplementation of choline-deficient cells with choline, dimethylethanolamine, monomethylethanolamine or ethanolamine resulted in an increase in the concentration of the corresponding phospholipid. Release of cytidylyltransferase into cytosol was only observed in hepatocytes supplemented with choline or dimethylethanolamine. The apparent EC50 values (concn. giving half of maximal effect) for cytidylyltransferase translocation were similar for choline and dimethylethanolamine (25 and 27 microM respectively). The maximum amount of cytidylyltransferase released into cytosol with choline supplementation (1.13 m-units/mg membrane protein) was twice that (0.62) observed with dimethylethanolamine. Supplementation of choline-deficient hepatocytes with NN'-diethylethanolamine, N-ethylethanolamine or 3-aminopropanol also did not cause release of cytidylyltransferase from cellular membranes. The translocation of cytidylyltransferase appeared to be mediated by the concentration of phosphatidylcholine in the membranes and not the ratio of phosphatidylcholine to phosphatidylethanolamine. The results provide further evidence for feedback regulation of phosphatidylcholine biosynthesis by phosphatidylcholine.

Animals↗

Choline deficiency causes translocation of CTP:phosphocholine cytidylyltransferase from cytosol to endoplasmic reticulum in rat liver.

The choline-deficient rat liver has been chosen as a physiologically relevant model system in which to study the regulation of phosphatidylcholine biosynthesis. When 50-g rats were placed on a choline-deficient diet for 3 days, the activity of CTP:phosphocholine cytidylyltransferase (CT) was increased 2-fold in the microsomes and decreased proportionately in the cytosol. A low titer antibody to CT was obtained from chickens and used to identify the amount of CT protein in cytosol from rat liver. The amount of CT recovered from the choline-deficient cytosol was significantly less than in cytosol from choline-supplemented rats. When hepatocytes were prepared from choline-deficient livers, supplementation of the medium of the cells with choline caused CT to move from the membranes to cytosol within 1-2 h. The activity of another translocatable enzyme of glycerolipid metabolism, phosphatidate phosphohydrolase, was unchanged in cytosol from choline-deficient rat livers, and the microsomal activity of this enzyme was only minimally increased. When the livers were fractionated into endoplasmic reticulum and Golgi, there was a 2-fold increase in the activity on the endoplasmic reticulum from choline-deficient livers but no change in activity associated with Golgi. Thus, the increased association of CT with endoplasmic reticulum in choline-deficient livers appears to be specific to that subcellular fraction, and the subcellular location of other enzymes may not be affected.

Animals↗

Feedback regulation of CTP:phosphocholine cytidylyltransferase translocation between cytosol and endoplasmic reticulum by phosphatidylcholine.

The mechanism for the increased association of CTP:phosphocholine cytidylyltransferase (CT) with membranes of hepatocytes derived from choline-deficient, compared with choline-supplemented rats, has been investigated. The cells were maintained in culture for 4 h in a choline- and methionine-deficient medium. (Methionine is required for synthesis of phosphatidylcholine (PC) via methylation of phosphatidylethanolamine.) Afterward, the cells were incubated +/- choline for various times up to 4 h. In the presence, but not in the absence, of choline there was a translocation of CT activity from membranes to cytosol. During this time period there was no change in the amounts of unesterified fatty acids or diacylglycerol recovered from the hepatocytes. In addition, there was no evidence for a difference in the incorporation of 32P into CT or other cytosolic proteins isolated from hepatocytes +/- choline. In contrast, there was a highly significant correlation between the concentration of PC in the membranes and the increased activity of CT in the cytosol (R = 0.98) and the decreased activity in the membranes (R = 0.93). The concentration of PC could alternatively be altered by incubation of the choline-deficient hepatocytes with methionine or lyso-PC. With either of these supplementations highly significant correlation coefficients were observed between the concentration of PC in membranes and decreased activity of CT in membranes or increased activity in cytosol. The concentration of PC was reduced in the endoplasmic reticulum, but not the Golgi membranes, isolated from choline-deficient compared with choline-supplemented livers. The data suggest that the amount of PC in the endoplasmic reticulum feedback regulates the amount of CT associated with this membrane.

Biological Transport↗

Acute poisoning--a review of 1900 cases.

A review of nineteen hundred cases of acute poisoning admitted to the Intensive Care Unit shows that poisoning was responsible for 40% of the emergencies treated at this Unit, between 15th January, 1976 to 15th November, 1985. Comparing our data with Western figures, it was noted that the pattern of poisoning in our Country is considerably different from that in the West. Organophosphorus insecticide Poisoning was by far the commonest in our series and was responsible for the majority of fatal cases. Over-all mortality rate for all the other poisons excluding Organophosphorus Insecticide compared favourably with Western figures, being 1.8%.

Adolescent↗

Organophosphorus insecticide poisoning.

A review of 755 cases of Organophosphorus Insecticide Poisoning, admitted to the department of Intensive Care at the Jinnah Postgraduate Medical Centre between 15th January, 1976 to 31st December 1985, has shown that these insecticides form a majority of the cases of acute poisoning and are associated with a comparatively higher mortality rate. Of 1900 cases, 755 were cases of organophosphorus insecticide poisoning forming 39.7% of the total poisoning cases and 16% of the total admissions to the Unit. Being easily accessible, these insecticides are frequently used as suicidal agents specially by uneducated housewives. They are highly toxic and their management is very complicated. Of 108 deaths from poisoning in the last 10 years 73 (67.6%) were due to Organophosphorus Insecticide Poisoning. This being such a common mode of poisoning in our country, we have presented here our experience of the clinical features and management of these cases.

Adolescent↗

Phosphorylation state of acetyl-coenzyme A carboxylase. I. Linear inverse relationship to activity ratios at different citrate concentrations.

Acetyl-CoA carboxylase and its associated kinase have been purified to homogeneity from rat liver and, together with the catalytic subunit of liver protein phosphatase, used to study the effect of phosphorylation on the carboxylase activity. Phosphatase increases the carboxylase activity, whereas the kinase decreases it. A linear inverse relationship (correlation coefficient = 0.98) exists between phosphate incorporated by the kinase and the specific activity. The kinetics of activation by citrate show an increased Ka and a decreased Vmax for carboxylase preparations with increasing levels of phosphate. On this basis an enzymic test was devised for phosphate incorporated by the kinase. Thus the ratio of activities at 0 and 2 mM citrate is inversely proportional to the phosphate incorporated (correlation coefficient = -0.95), with 0.8 mol of P incorporated per mol of subunit decreasing the activity ratio from 0.5 to 0. This activity ratio method has an inherent internal control which makes it suitable for determining the level of protein-bound phosphate affecting the carboxylase activity in crude tissue extracts, and hence it should be useful for physiological studies. Tryptic maps of carboxylase labeled with radioactive phosphate by the carboxylase kinase indicate that the slightly less than 1 mol of P/mol of subunit is distributed equally between two peptides, whereas cAMP-dependent protein kinase phosphorylates these two sites and a third which may not affect activity.

Acetyl-CoA Carboxylase↗

Phosphorylation state of acetyl-coenzyme A carboxylase. II. Variation with nutritional condition.

Acetyl-CoA carboxylase from liver exhibits a linear inverse relationship between the ratio of enzymic activities at 0 and 2 mM citrate and the extent of phosphorylation by its kinase, and this citrate activity ratio method was used to examine the effect of nutritional conditions on the phosphorylation state of the enzyme. This method showed that the calculated phosphorylation state, being the extent of phosphorylation at sites accessible to carboxylase kinase, was highest in the livers of starved rats, lower in those fed normally, and lower still in starved rats which had been refed for 48 h on a fat-free diet. The actual values were 0.44, 0.26, and 0 mol of P/subunit, respectively, provided that liver samples were frozen rapidly to liquid nitrogen temperatures and extracted with stopping buffers at temperatures well below freezing. Normal homogenization with stopping buffers (containing inhibitors for protein kinases and phosphatases) resulted in much higher calculated phosphorylation states. The effect of nutritional conditions on the phosphorylation state as estimated reported above was confirmed by purifying the carboxylase from livers of rats, measuring the amount of phosphate which could be incorporated by carboxylase kinase, and comparing this with the phosphorylation state calculated from the citrate activity ratio method or the specific activity. Furthermore, treatment with protein phosphatase of carboxylase from starved rats resulted in the largest increase in specific activity, that from the starved/refed rats in the least. Finally, the effects of hyperglycemia on carboxylase and phosphorylase characteristics in the livers of intact rats were ascertained by taking liver samples and preparing crude extracts by the rapid freezing method described above. Hyperglycemia caused a rapid increase in the activity of the carboxylase and a rapid decrease in its putative phosphorylation state as measured by the citrate activity ratio method. Phosphorylase was also dephosphorylated, as indicated by a decrease in phosphorylase a activity. We conclude that the citrate activity ratio method is a valid test for the phosphorylation state of acetyl-CoA carboxylase in crude extracts of tissue.

Acetyl-CoA Carboxylase↗

Mechanism of action of rabbit liver phosphoglucomutase.

Induced-transport tests with comparatively undegraded rabbit liver phosphoglucomutase show that the enzyme possesses a phosphoenzyme mechanism and that any interconversion of phosphoenzyme forms is very rapid. A relatively stable 32P-labelled phosphoenzyme was isolated, which exchanged label rapidly with substrates. The phospho group appears to be bonded to a serine residue on the enzyme.

Animals↗

Patients with acute poisoning seen in the department of intensive care-Jinnah Postgraduate Medical Centre, Karachi.

A review of 157 cases of acute poisoning admitted to the intensive care unit shows that poisoning was responsible for 40 15% of the cases treated at this unit between 15th January to 31st December, 1976. Inspite of limited facilities the over all mortality from acute poisoning was 9.5% while that due to organo-phosphorus insecticides alone was 7%. A considerable infrequency of organophosphorus insecticides poisoning was observed in developed countries when their data was compared with the present series.

Adolescent↗

Organo-phosphorus insecticide poisoning-review of 53 cases.

A review of 53 cases of organo-phosphorus insecticide poisoning admitted to the department of intensive care at the Jinnah Postgraduate Medical Centre between 15th January to 31st December, 1976 has shown that these insecticides form a majority of the causes of acute poisoning and are associated with a comparatively high mortality rate. Out of a total of 157 cases of acute poisoning admitted to the department, 34% were cases of organo-phosphorus insecticide poisoning forming 13 5% of the total admissions. These insecticides being easily accessible, are frequently used as suicidal agents specially by uneducated housewives. They are highly toxic and their management is very complicated. Of a total of 15 deaths from poisoning, 11 (73%) were due to this cause. This being such a common mode of poisoning in our country, we have presented here our experience of the clinical features and management of these cases.

Adolescent↗