Riley MS, Nicholls DP, Cooper CB

Ann Am Thorac Soc. 2017 Jul;14(Supplement_1):S129-S139. doi:
10.1513/AnnalsATS.201701-014FR

Skeletal muscle requires a large increase in its ATP production to meet the
energy needs of exercise. Normally, most of this increase in ATP is supplied by
the aerobic process of oxidative phosphorylation. The main defects in muscle
metabolism that interfere with production of ATP are (1) disorders of
glycogenolysis and glycolysis, which prevent both carbohydrate entering the
tricarboxylic acid cycle and the production of lactic acid; (2) mitochondrial
myopathies where the defect is usually within the electron transport chain,
reducing the rate of oxidative phosphorylation; and (3) disorders of lipid
metabolism. Gas exchange measurements derived from exhaled gas analysis during
cardiopulmonary exercise testing can identify defects in muscle metabolism
because [Formula: see text]o2 and [Formula: see text]co2 are abnormal at the
level of the muscle. Cardiopulmonary exercise testing may thus suggest a likely
diagnosis and guide additional investigation. Defects in glycogenolysis and
glycolysis are identified by a low peak [Formula: see text]o2 and absence of
excess [Formula: see text]co2 from buffering of lactic acid by bicarbonate.
Defects in the electron transport chain also result in low peak [Formula: see
text]o2, but because there is an overreliance on anaerobic processes, lactic acid
accumulation and excess carbon dioxide from buffering occur early during
exercise. Defects in lipid metabolism result in only minor abnormalities during
cardiopulmonary exercise testing. In defects of glycogenolysis and glycolysis and
in mitochondrial myopathies, other features may include an exaggerated
cardiovascular response to exercise, a low oxygen-pulse, and excessive ammonia
release.