Search PubMed⌕ Search

Biomedical subjects

F Snyder

Publications and source records attributed to F Snyder.

At least 127 records · Page 7Linked to original sources
PubMed1982

Cardiovascular and sympathetic effects of l-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine in conscious SHR and WKY rats.

Injections of 1-)-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (alkylacetyl-GPC, 0.2-5.0 nmol/300 g body weight) induced dose-related hypotension and tachycardia in spontaneous hypertensive (SHR) and normotensive control (WKY) rats. The hypotension that developed was more pronounced in SHR than in WKY rats and was unchanged by indomethacin pretreatment. Plasma norepinephrine (NE) and epinephrine (EPI) levels were markedly increased at the time of maximal hypotension (2 min after injection of alkylacetyl-GPC); plasma EPI (but not NE) was higher in the SHR than in WKY animals. Plasma levels of TXB2, but not 6-keto-PGF 1 alpha, increased in both groups; the increase was more pronounced in SHR than in WKY rats. In pithed SHR rats, alkylacetyl-GPC caused only short lasting hypotension without any effect on heart rate or circulating levels of NE or EPI. These data suggest that there is an increased vascular sensitivity to alkylacetyl-GPC in SHR rats and activation of thromboxane-generating elements in both SHR and WKY rats.

Animals↗
PubMed1982

Structural features of platelet activating factor (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) required for hypotensive and platelet serotonin responses.

A number of analogs similar in structure to biologically active 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet activating factor) were tested for their relative effectiveness in lowering the blood pressure of spontaneous hypertensive rats and in releasing [3H]serotonin from rabbit platelets. Except for some minor variations, the two test systems gave the same pattern of relative responses for a given analog. Both biological activities (the antihypertensive response and release of platelet serotonin) appear to be stereospecific since the unnatural isomer exhibited no detectable effects. Other structural modifications that greatly reduced (greater than 500-fold) or eliminated the two biological activities were: 1) removal of the acetate group, 2) substitution of the acetate group with long-chain acyl, methoxy, benzoxy, N-formyl, N-trifluoroacetyl, N-hexadecanoyl, or deoxy groups such as dimethyl, propyl, isopropyl, or isobutyl, and 3) replacement of the sn-1 0-alkyl group with an acyl moiety. Biological activities were reduced to a lesser extent (100- to 500-fold) when the sn-2 carbon contained butyrate or hexanoate groups or if ethanolamine was substituted for the choline base. Replacing the sn-2 acetate group with an ethoxy group lowered the activity 48- and 120-fold for the blood pressure and serotonin release, respectively. Substitution of propionate for acetate at the sn-2 carbon gave a compound that was at least, if not more, biologically active than the parent structure; although an N-acetyl analog possessed biologic activities, the responses were only 0.27 to 1.0% of those obtained with the O-acetyl lipid. Maximum biological activity for both hypotensive effects and platelet serotonin release required a glycerolipid having an alkyl ether at the sn-1, acetate or propionate groups at the sn-2, and phosphocholine at the sn-3 positions.

Animals↗
PubMed1981

Transmembrane orientation of palmitoyl-CoA: lysophosphatidylcholine acyltransferase in microsomes isolated from an alveolar type II cell adenoma and rat liver.

1. The transverse localization of palmitoyl-CoA : lysophosphatidylcholine acyltransferase in the membrane of microsomal vesicles isolated from mouse lung adenomas and rat liver was studied by treating intact and deoxycholate-disrupted microsomes with trypsin and pronase. 2. The latency of mannose-6-phosphatase was preserved during protease treatment, suggesting that membrane integrity was not affected. 3. In adenoma microsomes 35-50% and in liver microsomes 35% of lysophosphatidylcholine acyltransferase activity is accessible to the action of the proteases. Our results suggest that at least a sizable portion of the active center of the enzyme that is responsible for remodeling phospholipids is embedded in the membrane interior. 4. Since enzymes involved in de novo lipid synthesis are reported to be located at the cytoplasmic surface of the microsomal membrane, our results support the notion that in lipid metabolism distinct metabolic pools might exist at opposite sides of the microsomal membrane.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed1981

Biosynthesis of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet activating factor and a hypotensive lipid) by cholinephosphotransferase in various rat tissues.

The unique alkyl phospholipid, 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine, has been reported to exhibit powerful antihypertensive activity (Blank, M.L., Snyder, F., Byers, L.W., Brooks, B. and Muirhead, E.E. (1979) Biochem. Biophys. Res. Commun. 90, 1194-1200) and appears to be an extremely potent platelet-activating factor (Demopoulos, C.A., Pinckard, R.N. and Hanahan, D.J. (1979) J. Biol. Chem. 254, 9355-9358). In the present study, microsomal preparations from several rat tissues were found to catalyze the synthesis of 1-alkyl-1-acetyl-sn-glycero-3-phosphocholine by 1-alkyl-2-acetyl-sn-glycerol:CDPcholine cholinephosphotransferase reaction. Optimal conditions to measure enzyme activity were established. A subcellular survey of this cholinephosphotransferase activity showed that the enzyme was of microsomal origin. Enzyme activity was found in microsomes from several tissues; however, spleen has the highest activity of the tissues examined. Three different species of 1-alkyl-2-acetyl-sn-glycerol were all found to be substrates. The 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine synthesized in the microsomes could be hydrolyzed by adding the 100,000 x g supernatant fraction to the incubation medium. The optimum pH for formation of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine was 8.0, which was different from the pH optimum of 8.5 observed for the long-chain diacylglycerol cholinephosphotransferases. Activity of cholinephosphotransferase towards 1-alkyl-2-acetyl-sn-glycerol was slightly enhanced and stabilized by dithiothreitol, whereas the activity towards a diacylglycerol was inhibited by dithiothreitol. The possible involvement of two different enzymes in the conversion of 1-alkyl-2-acetyl-sn-glycerol and diacylglycerol to their respective phospholipid products is discussed.

Animals↗
PubMed1981

A specific acetylhydrolase for 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (a hypotensive and platelet-activating lipid).

1-Alkyl-2-acetyl-sn-glycero-3-phosphocholine, a phospholipid with platelet activating and hypotensive properties, has an extremely labile acetate grouping. The acetate group is obviously important in the expression of the biological properties of this unique derivative of plasmanic acid since once it is hydrolyzed from the parent compound to form the lyso product, all biological activity is lost. Our studies show that the enzyme responsible for the hydrolysis of the acetate moiety, 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine: acetylhydrolase, occurs in the cytosolic fraction of a variety of tissues and has a pH optimum of 7.5 to 8.5. Effects of calcium, magnesium, EDTA, dithiothreitol, deoxycholate, and diisopropylfluorophosphate on the enzyme activity and the fact that egg phosphatidylcholine was not inhibitory indicate that acetylhydrolase activity has different properties from those normally associated with the phospholipase A2 that utilizes phospholipids with two long chain acyl groups. The highest specific activity of the acetylhydrolase occurred in kidney; lung and brain were also good sources of the enzyme. The soluble fraction from the kidney cortex had an apparent Km and Vmax of 3.1 microM and 17.8 nmol/min/mg of protein, respectively. Our results indicate that acetylhydrolase plays a significant role in the catabolism of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine.

Animals↗
PubMed1980

Enzymatic synthesis of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine, a hypotensive and platelet-aggregating lipid.

1-Alkyl-2-acetyl-sn-glycero-3-phosphocholine, derived chemically from choline plasmalogens of beef heart, has been shown to possess powerful antihypertensive activity (Blank, M. L., Synder, F., Byers, L. W., Brooks, B., and Muirhead, E. E. (1979) Biochem. Biophys. Res. Commun. 90, 1194-1200) and to be an extremely potent platelet-activating factor (Demopoulos, C. C., Pinckard, R. N., and Hanahan, D. J. (1979) J. Biol. Chem. 254, 9355-9358). In the present study, microsomal preparations of rat spleen were shown to synthesize 1-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine by an acetyl-CoA:1-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase reaction; the acetyltransferase appears to be different from the acyltransferase responsible for the transfer of palmitate to glycerolipids. The apparent Km for acetyl-CoA was 67 microM; the optimal concentration of 1-alkyl-2-lyso-sn-glycero-3-phosphocholine was 30 microM. Higher concentrations of the lyso substrate were inhibitory. When acetyl-CoA (100 microM) and 1-hexadecyl-sn-glycero-3-phosphocholine (30 microM) were incubated wih spleen microsomes under optimal conditions, the specific activity was approximately 10 nmol of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine/min/mg of protein. Although the reaction was inhibited by the addition of EDTA or EGTA to the incubation mixture, the acetyltransferase did not appear to require a divalent cation. An acyl analog, 1-palmitoyl-2-lyso-sn-glycero-3-phosphocholine, also served as a substrate for the acetyltransferase; however, the unnatural isomer, 3-alkyl-2-lyso-sn-glycero-1-phosphocholine, did not. The acetyltransferase activity was found in a variety of tissues, but the spleen had the highest activity of the tissues examined; lung, lymph nodes, and thymus also had high activities. Identification of the product and the possible physiological importance of the pathway are discussed.

Acetyltransferases↗
PubMed1980

Activities of enzymes involved in the metabolism of ether-linked lipids in normal and neoplastic tissues of rat.

We have compared the activities of three enzymes (acyl-CoA reductase, fatty alcohol:NAD+ oxidoreductase, and alkyl synthase) involved in the metabolism of ether lipids in rat liver and two tumors that contained various levels of ether lipids. The activity of fatty alcohol:NAD+ oxidoreductasee was high and the activities of acyl-CoA reductase and alkyldihydroxyacetone-P synthase were low in liver, which has low amounts of ether glycerolipids. On the other hand in Fischer R-3259 sarcoma, where high concentrations of ether-linked lipids were present, the reverse pattern was observed. In Morris hepatomas 5123C, with an intermediate value of ether lipids, the activities of all three enzymes ranged between that found in liver and Fischer sarcomas.

Acetone↗
PubMed1979

Regulation of ether lipids and their precursors in relation to glycolysis in cultured neoplastic cells.

Tumors typically show high rates of glycolysis and elevated levels of ether lipids, particularly the alkyldiacylglycerols; thus, we investigated the relationship between ether lipid accumulation and glucose metabolism in a neoplastic cell line (B2-1). The B2-1 cells grown in 5.5 mM galactose in the absence of glucose produced very low levels of alkyldiacylglycerols, triacylglycerols, lactic acid, and dihydroxyacetone-P. Increasing concentrations of glucose caused a progressive increase in lactic acid, dihydroxyacetone-P, and up to a ten-fold increase in alkyldiacylglycerols and triacylglycerols. Glucose supplements also caused an increased incorporation of [9,10-3H]palmitic acid into alkyldiacylglycerols and triacylglycerols. These metabolic changes appeared to be independent of altered growth rates of the cells. The addition of hexadecanol along with glucose to the cultures resulted in a shorter lag and a more rapid rate of accumulation of alkyldiacylglycerols; hexadecanol supplements alone had no effect. The extent of uptake and oxidation of hexadecanol was similar in both the glucose and galactose-grown cells. These results indicate that the levels of alkyldiacylglycerols in neoplastic cells can be regulated by the extent their precursors are formed from glucose.

Animals↗