Quantitative analysis by 31P magnetic resonance spectroscopy of abnormal mitochondrial oxidation in skeletal muscle during recovery from exercise.
We use the hyperbolic relationship between cytosolic [ADP] and the rate of phosphocreatine (PCr) resynthesis after exercise to estimate the apparent maximum rate of oxidative ATP synthesis (QMAX). We examine data from some human diseases in which mitochondrial oxidation may be impaired (due to reduced mitochondrial numbers, intrinsic mitochondrial defect or impaired vascular supply). Muscle responds to impaired oxidation by stimulating anaerobic ATP synthesis and/or by increasing [ADP], the stimulus to the mitochondrion. However, these responses interact: [ADP] depends on pH and [PCr], and lactic acid production tends to lower [ADP] (by lowering pH), while proton efflux has the opposite effect. We identify four patterns of results: (A) in mitochondrial myopathy, apparent QMAX is reduced and [ADP] is appropriately increased, because increased proton efflux reduces the pH change in exercise despite increased lactic acid production; (B) in some conditions (e.g., cyanotic congenital heart disease) apparent QMAX is reduced but there is no compensatory rise in [ADP], probably because anaerobic ATP synthesis during exercise is increased without increase in proton efflux; (C) in other conditions (e.g., myotonic dystrophy) [ADP] is increased during exercise but apparent QMAX is normal, suggesting either an increase in proton efflux and/or decrease in anaerobic ATP synthesis during exercise; (D) there are also conditions (e.g., respiratory failure) where, despite impaired oxygen supply, both apparent QMAX and end-exercise [ADP] are normal. We also discuss the metabolic conditions under which end-exercise [ADP] is increased by a mitochondrial defect.(ABSTRACT TRUNCATED AT 250 WORDS)
Kemp
G J
GJ
MRC Biochemical and Clinical Magnetic Resonance Unit, John Radcliffe Hospital, Oxford, UK.
Taylor
D J
DJ
Thompson
C H
CH
Hands
L J
LJ
Rajagopalan
B
B
Styles
P
P
Radda
G K
GK
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000293:Adolescent; D000368:Aged; D000693:Anaerobiosis; D002648:Child; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010725:Phosphocreatine / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D005082:Physical Exertion / Q000502:physiology*
D010761:Phosphorus Radioisotopes; D010725:Phosphocreatine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate