Lipids in Cryptomonas CR-1. II. Biosynthesis of Betaine Lipids and Galactolipids

The biosynthesis of lipids in Cryptomonas strain CR-1 was studiedusing radioactive tracers. For studies of general aspects ofthe biosynthesis of lipids, the cells were labelled with [¹⁴C]NaHCO₃or with [l,3-¹⁴]glycerol. In both cases, monogalactosyl diacylglycerol(MGDG) was the most heavily labelled lipid. Phosphatidylcholineand the alanine lipid DGTA were not labelled to specific activitiescomparable to those of MGDG and DGDG. It is improbable thatthe so-called "eukaryotic pathway", which has been suggestedas the pathway for the synthesis of " eukaryotic" molecularspecies of MGDG from PC in higher plants, is operative in Cryptomonascells which contain typical "eukaryotic" MGDG. The homoserinelipid DGTS was labelled to a significant level only in its polargroup. The C-3 and C-4 atoms of methionine, as well as the methylcarbon of methionine, were incorporated into both DGTS and DGTA,whereas the C-l carbon of methionine was incorporated uniquelyinto DGTS. Results of pulse-chase experiments with [3,4-¹⁴C]methionineand [methyl.-^l4C]methionine suggest the conversion of DGTS toDGTA. (Received April 22, 1991; Accepted June 12, 1991)     

Homocysteine and atherosclerosis.

Elevated plasma total homocysteine is an independent risk factor for atherosclerotic vascular disease. Risk rises continuously across the spectrum of homocysteine concentrations and may become appreciable at levels greater than 10 mumol/l. A compelling case can be made for screening all individuals with atherosclerotic disease or at high risk. A reasonable, but unproven, goal for treatment is a plasma total homocysteine concentration less than 10 mumol/l. Folic acid is the mainstay of treatment, but vitamins B12 and B6 may have added benefit in selected patients. The results of ongoing randomized placebo-controlled trials will not be available for several years, but will help determine whether homocysteine lowering reduces the risk of cardiovascular disease.     

Lipids of Leishmania promastigotes.

A chromatographic analysis of lipids of cultured promastigotes of Leishmania donovani, L. braziliensis, L. mexicana, L. tropica, L. enriettii, L. hertigi, L. adleri, and L. tarentolae showed that total lipids were 2--15% of dry wt, and neutral and polar lipids were 14--55% and 45--86% of total lipids. Major lipid classes were as follows: sterol ester, triacylglycerol, sterol, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylcholine. Predominant fatty acids were 18:2 (n - 6) greater than 18:3 (n - 3) greater than 18:1 (n - 9) greater than 18:0 greater than 22:6 (n - 3) greater than 22:5 (n - 6) greater than 16:0 greater than 14:0 greater than 18:4 (n - 3) greater than 20:3 (n - 3). Some remarkable distributions of fatty acids among the phospholipid fractions were observed, as follows: diphosphatidylglycerol 18--33% 22:6 (n - 3); phosphatidylinositol 31--68% 18:1 (n - 9); phosphatidylcholine 13--41% 18:3 (n - 3). Alk-l-enyldiacyl glycerols, and alk-l-enylacyl and alkylacyl forms of phosphatidylethanolamine and of phosphatidylinositol were found, and their glyceryl ethers and fatty adehydes analyzed. Notable in the phosphatidylethanolamine of some leishmanias was a cyclopropane fatty acid (4--11%), identified as cis-9,10-methylene octadecanoic acid by chromatographic, and by mass and proton resonance spectrometric analyses. The comparative biochemistry of the cyclopropane fatty acid, characteristic of many prokaryotes, and of alpha-linolenic acid, characteristic of photosynthetic plants, are commented upon.     

Nitric oxide and atherosclerosis.

Endothelial dysfunction has been shown in a wide range of vascular disorders including atherosclerosis and related diseases. Here, we examine and address the complex relationship among nitric oxide (NO)-mediated pathways and atherogenesis. In view of the numerous pathophysiological actions of NO, abnormalities could potentially occur at many sites: (a) impairment of membrane receptors in the arterial wall that interact with agonists or physiological stimuli capable of generating NO; (b) reduced concentrations or impaired utilization of l-arginine; (c) reduction in concentration or activity both of inducible and endothelial NO synthase; (d) impaired release of NO from the atherosclerotic damaged endothelium; (e) impaired NO diffusion from endothelium to vascular smooth muscle cells followed by decreased sensitivity to its vasodilator action; (f) local enhanced degradation of NO by increased generation of free radicals and/or oxidation-sensitive mechanisms; and (g) impaired interaction of NO with guanylate cyclase and consequent limitation of cyclic GMP production. Therefore, one target for new drugs should be the preservation or restoration of NO-mediated signaling pathways in arteries. Such novel therapeutic strategies may include administration of l-arginine/antioxidants and gene-transfer approaches.     

Lipid peroxides and atherosclerosis.

Plasma lipid peroxide concentrations were measured in 100 patients with occlusive arterial disease proved angiographically (50 patients with ischaemic heart disease, 50 with peripheral arterial disease) and compared with values in 75 control patients with no clinical evidence of atherosclerosis. Lipid peroxide concentrations were significantly higher in patients both with ischaemic heart disease (median 4.37 mumol/l (interquartile range 3.85-5.75 mumol/l); p less than 0.001) and with peripheral arterial disease (median 4.37 mumol/l (3.88-5.21 mumol/l); p less than 0.001) than in controls (median 3.65 mumol/l (interquartile range 3.29-3.89 mumol/l). Overall there was a significant but weak correlation between plasma lipid peroxide and plasma triglyceride concentrations (rs = 0.25; p less than 0.001) but not between plasma lipid peroxide and plasma total cholesterol concentrations. Furthermore, hypertension, obesity, diabetes, smoking, positive family history, and intake of beta blockers and thiazide diuretics were not associated with significant differences in lipid peroxide values. This study provides clinical support to experimental data indicating that peroxidised lipids may be important in atherogenesis and its complications and also suggests that peroxidised lipids may provide an index of the severity of atherosclerosis.