Question

he metabolic pathways of cardiac muscle make it

Answer 1

The heart is capable of utilizing all classes of energy substrates, including carbohydrates, lipids, amino acids and ketone bodies, for ATP production in the mitochondrion (Figure 1, for details see reviews1-3). Mitochondria occupy one third of the cell volume in cardiac myocytes making them the cell type with the highest mitochondria content.4 The robustness of cardiac metabolism is reflected by its highest oxygen consumption rate on the per unit weight basis. For a human heart, the amount of ATP turned over during a one-day period is 15-20 times of its own weight. In a normal heart, mitochondria are largely fueled by fatty acyl-CoA and pyruvate, which are the primary metabolites of fatty acids and carbohydrates, respectively. The entry of long-chain acyl-CoA into the mitochondrion is a regulated process; with the rate-limiting step at the muscle form of the carnitine-palmitoyl transferase I (mCPT-1) reaction. The oxidation of pyruvate is regulated at the pyruvate dehydrogenase (PDH) reaction. Other substrates, including lactate, ketone bodies and amino acids, can enter mitochondria directly for oxidation. Metabolism of ketone bodies yields acetyl-CoA while amino acid catabolism yields keto-acids which are further metabolized to enter the TCA cycle. The contribution of ketone bodies and amino acids to overall cardiac oxidative metabolism is considered to be minor due to the low availability of these substrates under normal physiological conditions.

The energy-yielding substrates (fatty acids, glucose, ketones, and amino acids), via specific catabolic pathways, converge on acetyl CoA production with subsequent entry into the tricarboxylic acid (TCA) cycle. The final step of energy transfer is accomplished through oxidative phosphorylation (OxPhos), supplying greater than 95% of ATP consumed by the heart. The boxes (in pink) above each metabolic pathway indicate the pathological and/or physiological condition in which the specific substrate becomes a predominant contributor to metabolism. TAG, triacylglycerol; DGAT, diacylglycerol acyltransferase; ATGL, adipose triglyceride lipase; mCPT1, muscle form of carnitine palmitoyl transferase; PDH, pyruvate dehydrogenase; TCA, tricarboxcylic acid; O2,oxygen.