and inhibition of PFK, thus slowing the rate of
glycolysis and glycogenolysis. This forms the
basis of the ‘glucose–fatty acid cycle’ proposed
by Randle et al. (1963), which has for many years
been accepted to be the key regulatory mecha-
nism in the control of CHO and fat utilization by
skeletal muscle. However, recent work has chal-
lenged this hypothesis and it seems likely that
the regulation of the integration of fat and CHO
catabolism in exercising skeletal muscle must
reside elsewhere, e.g. at the level of glucose
uptake into muscle, glycogen breakdown by
phosphorylase or the entry of fatty acids into the
mitochondria. A detailed discussion is beyond
the scope of this review; for further details, see
Hargreaves (1995) and Maughan et al. (1997).
biochemistry of exercise 31
Muscle glycogen
1
+
+
AMP, Pi, Ca2+, adrenaline (cAMP)
ATP
ADP
Glucose-1-P
Glucose-6-P
Fructose-6-P
Fructose-1,6-bp
PEP
Pyruvate
5
Acetyl-CoA
Oxaloacetate
TCA cycle
Succinyl-CoA
α-ketoglutarate
Citrate
ATP
NADH
ATP, NADH
Ca2+, ADP, CoA, NAD+
4
3
2
10
9
8
6
7
Glucagon, adrenaline,
noradrenaline
Insulin
Liver glycogen
Plasma glucose
Adipose tissue and
muscle
triacylglycerol
Adrenaline, glucagon,
cortisol
Insulin
Fatty acids
Fatty acyl-CoA
β-oxidation
NAD+
Muscle protein
Cortisol
Insulin
ADP, AMP, Pi, NH+ 4
ATP, H+
Activators
Inhibitors
Amino acids
+
+
+
+
+
+
Fig. 2.6Metabolic pathways of importance to energy provision during exercise showing the main sites of
regulation and the principal hormonal and allosteric activators and inhibitors. Enzymes: 1 , glycogen
phosphorylase (muscle); 2 , glycogen phosphorylase (liver); 3 , hexokinase; 4 , phosphofructokinase; 5 , pyruvate
dehydrogenase; 6 , hormone-sensitive lipase; 7 , carnitine acyl-transferase; 8 , 3-hydroxyacyl dehydrogenase; 9 ,
citrate synthase; 10 , proteases. AMP, adenosine monophosphate; cAMP, cyclic AMP; PEP, phosphoenolpyruvate;
Pi, inorganic phosphate; TCA, tricarboxylic acid.