Arthur F. Whereat

The preparation of serum lipoproteins labeled with radioactive cholesterol

Abstract Cholesterol-4-C14 in a Tween 20 dispersion was found to exchange readily with the cholesterol of plasma lipoproteins. This proved to be a rapid and simple method for preparing lipoprotein which contains radioactive cholesterol. On the basis of electrophoretic, ultracentrifugal, and immunochemical evidence presented, it is concluded that this is a true isotope exchange and that the physical properties of the lipoproteins studied are not altered.

Fatty Acid Biosynthesis in Aorta and Heart

Publisher Summary Fatty acid synthesis occurs in both cytosol and mitochondria of most organs, although one or the other system predominates in a given organ. This chapter discusses fatty acid biosynthesis in aorta. It discusses in which cellular subfraction fatty acid synthesis occurs. On the basis of current information, the three cellular subfractions from aorta are capable of incorporation of substrate into fatty acids. Using acetate or acetyl–CoA as the precursor, mitochondria have the greatest synthetic capacity. When malonyl–CoA is the precursor, the cytosol has the greatest capacity. The chapter discusses the pathways for fatty acid synthesis that have been shown to be present in aorta. The mitochondrial elongation system is well developed and utilizes acetyl–CoA and available acyl–CoA to produce a variety of chain lengths of saturated and unsaturated fatty acids. The spectrum of fatty acids synthesized by the whole aorta or its constituent subfractions is not notably different from that of other organ. The chapter also discusses fatty acid biosynthesis in the heart and reviews the mechanism, products, and regulation of synthesis of fatty acids in the heart.

Aortic Mitochondrial Synthesis of Lipid and Its Response to Cholesterol Feeding

The rates and products of lipid synthesis from acetate-I-14C were studied in mitochondria isolated from control and atherosclerotic rabbit aorta. More acetate was incorporated into fatty acids in the cholesterol-fed animals. The mechanism was one of chain elongation, and the resultant products were longer in chain length. The newly elongated fatty acids were esterified mostly into phospholipids, presumably those turning over most rapidly. A hypothesis is proposed for the pathogenetic sequence: Cholesterol feeding alters transport functions of the mitochondrial membranes of aortic smooth muscle cells. Respiration and redox state are altered and consequently acetate is incorporated more rapidly into fatty acids as an alternate mechanism for oxidation of the reduced form of nicotin-amide-adenine dinucleotide (NADH). Rapidly turning over phospholipids esterify these fatty acids and may transfer them ultimately to cholesterol. Esterified cholesterol is less exchangeable and commences to accumulate.

The effect of cholesterol administration on lipid biosynthesis by rabbit aortic mitochondria

Abstract An aqueous suspension of cholesterol (5.0 gm/day) was administered by stomach tube to 19 rabbits for 18–22 days. The rate of acetate incorporation into fatty acids and complex lipids was measured in isolated aortic mitochondria from the experimental and control animals, both of which were on an otherwise similar low-fat diet. Following cholesterol administration, acetate-1- 14 C was incorporated into fatty acids at a faster rate and the distribution of label into complex lipids and specific fatty acids was altered. In the control mitochondria the complex lipids acquiring the largest percentages of 14 C were: unesterified fatty acids (42%), phosphatidyl ethanolamine (20%), and lecithin (13%); the majority of labeled fatty acids were those emerging from the gas-liquid chromatographic column after C 18:3 . Following cholesterol administration, the most impressive changes were the large increases in percentages of label appearing in phosphatidic acid and octadecadienoic acid (C 18:2 ), indicating an increased rate of turnover of these species. These described changes in mitochondrial lipid turnover are additions to the still growing list of physiological and biochemical consequences of cholesterol feeding. Understanding their functional interrelations may ultimately reveal the mechanism of lesion formation.

Incorporation of Tritium from Succinate-2,3-H.3 into Long Chain Fatty Acids by Aortic Mitochondria.∗

Summary The mechanism of succinate stimulation of fatty acid synthesis by aortic mitochondria was studied. Tritium, but not carbon, from succinate labeled in positions 2- and 3- is incorporated into long-chain fatty acids in this system. The relative incorporation of tritium in various fatty acids is similar to that of C14 from acetate. Succinate can, therefore, provide protons for the reductive steps. We believe this is a demonstration of energy-requiring reversal of electron flow participating in a synthetic process and another way in which Krebs Cycle acids can influence fatty acid synthesis.

Alcohol in Toxic Congestive Cardiomyopathy

Though ethyl alcohol is known to be one of the exogenous toxins that can directly damage the myocardium, nonalcoholic additives to alcoholic beverages (as well as poor nutrition or viral infection) may also play a role in cardiomyopathy. The authors note the interesting fact that, unlike the liver, the heart does not contain an alcohol dehydrogenase and thus lacks a possible protective mechanism against alcohols toxicity.