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Outline
Regulation of metabolic pathways in the
heart
Carbohydrate metabolism
Fatty acid metabolism
Ketone body metabolism
Interregulation of fatty acid and
carbohydrate oxidation
Effects of substrate selection on contractile
function and efficiency
Regulation of Metabolic
Pathways in the Heart
Oxidative phosphorylation
Carbohydrate Metabolism
Carbohydrate Metabolism
In the well-perfused heart, 6090% of the
acetyl- CoA comes from -oxidation of
fatty acids, and 10 40% comes from the
oxidation of pyruvate that is derived in
approximately equal amounts from
glycolysis and lactate oxidation
Carbohydrate Metabolism
The glycolytic pathway converts glucose
6-phosphate and NAD to pyruvate and
NADH and generates two ATP for each
molecule of glucose
Carbohydrate Metabolism
The NADH and pyruvate formed in
glycolysis are either shuttled into the
mitochondrial matrix to generate CO2 and
NAD and complete the process of aerobic
oxidative glycolysis or converted to lactate
and NAD in the cytosol (nonoxidative
glycolysis)
Carbohydrate Metabolism
Glycolytic substrate is derived from
exogenous glucose and glycogen stores
Glucose transport into cardiomyocytes is
regulated by the transmembrane glucose
gradient and the content of glucose
transporters in the sarcolemma (mainly
GLUT-4, and to a lesser extent GLUT-1)
Carbohydrate Metabolism
An additional source of glucose 6-phosphate
for the heart is intracellular glycogen stores
Glycogen concentrations are increased by an
elevated supply of exogenous substrate
and/or hyperinsulinemia, and glycogenolysis
is activated by adrenergic stimulation, a fall in
the tissue content of ATP, and a rise in
inorganic phosphate such as occur with
ischemia or intense exercise
Carbohydrate Metabolism
Glycolytic enzymes are clustered near the
sarcoplasmic reticulum and sarcolemma
Carbohydrate Metabolism
The pyruvate formed from glycolysis has
three main fates: conversion to lactate,
decarboxylation to acetyl- CoA, or
carboxylation to oxaloacetate or malate
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