Utilization of carbohydrate and fatty acids is strongly influenced by rates of con­ sumption and production of high energy compounds in cardiac muscle. In well­ oxygenated hearts, fatty acid has been identified as the preferred substrate by both in vivo and in vitro studies (for review see 146). Availability of fatty acid suppresses glucose utilization by inhibition of several steps in the glycolytic pathway. Since a variety of longand short-chained fatty substrates are inhibitory and since the effect is abolished in hearts perfused under anaerobic conditions, oxidation of the fatty acid appears to be required for this effect. When energy utilization of well­ oxygenated hearts is increased, consumption of fatty acids and/or glucose is ac­ celerated. Under these conditions, fatty acids remain the preferred oxidative substrate. Availability of oxygen to the heart can be restricted either by lowering or reducing to zero the oxygen tension of the perfusate, thereby inducing hypoxia or anoxia, or by restricting the flow of perfusate containing high oxygen tensions to induce ischemia. In hypoxic or anoxic hearts, fatty acid oxidation is suppressed and glycol­ ysis is stimulated. The acceleration of flux through glycolysis may be as much as 10to 20-fold. On the other hand, ischemia results in only a transient increase in glycolytic flux that is followed within 3-4 min by inhibition. Fatty acid oxidation is suppressed in ischemic hearts leading to accumulation of long-chained CoA derivatives and increase in triglyceride levels.

Relationship Between Carbohydrate and Lipid Metabolism and the Energy Balance of Heart Muscle

Lipids of nervous tissue: composition and metabolism.

A ROLE for abnormal lipid metabolism in the pathogenesis of atherosclerosis was suggested over a century ago, when Virchow proposed that transport of plasma lipids into the walls of blood vessels contributed to the development of atheromatous lesions. Lipid abnormalities are now firmly established as one factor leading to ischemic heart disease, although the mechanism by which they lead to coronary artery occlusion remains incompletely understood. More recently, abnormalities of lipid metabolism have been implicated in another quite different aspect of the pathogenesis of ischemic heart disease. A large body of evidence now indicates that altered lipid metabolism can alter cardiac function by changing the properties of cardiac cell membranes, and that these functional changes may contribute to the decline in myocardial contractility, the arrhythmias, and the eventual cell death that follow coronary artery occlusion. This article will review some of these disorders in lipid metabolism and possible mechanisms by which they might modify membrane function in the ischemic heart. Disorders of Lipid Metabolism in the Ischemic Heart There are now at least three well-defined mechanisms by which lipid metabolism may be altered in the heart after coronary artery occlusion (Table 1). Each of these mechanisms has been implicated in the pathogenesis of the cardiac abnormalities seen in patients who sustain an acute myocardial infarction.

BRIEF REVIEWS Lipid-Membrane Interactions and the Pathogenesis of Ischemic Damage in the Myocardium

Lipid-membrane interactions and the pathogenesis of ischemic damage in the myocardium.

In a rare myopathy muscle fibers contained myriad lipid-filled vacuoles. Homogenates of the patient's muscle oxidized fatty acids more slowly than normal (11 controls). Addition of carnitine increased the oxidation rate with the patient's muscle to the level attained by the controls with carnitine. In five separate muscle samples from the patient the mean carnitine level was less than 20 percent of that observed in 42 controls. Carnitine palmityl transferase and palmityl thiokinase levels in the patient's muscles were not depressed. The present case represents the first recognized instance of carnitine deficiency in human skeletal muscle.

https://science.sciencemag.org/content/sci/179/4076/899.full.pdf

S.V. Pande

Papers

Long chain fatty acid activation in subcellular preparations from rat liver.

Inhibition of Enzyme Activities by Free Fatty Acids

Distribution of long-chain fatty acid-activating enzymes in rat tissues.

Inhibition of the Stearyl Coenzyme A Desaturase System by Sterculate