Adenine nucleotide depletion in human muscle during exercise: causality and significance of AMP deamination.
The predominant route for adenine nucleotide catabolism in skeletal muscle is deamination of AMP to inosine monophosphate (IMP) and ammonia (NH3). Deamination of AMP is enhanced during exercise when the capacity to rephosphorylate ADP is impaired. Thus, in human muscle the formation of IMP (NH3) during exercise is augmented under the following conditions (1) at high intensities, (2) during beta-adrenoceptor blockade, (3) during hypoxia, (4) after detraining, and (5) at low glycogen levels. The formation of IMP is related to the metabolic stress (as indicated by the degree of phosphocreatine breakdown and lactate accumulation), the rate of ATP turnover, and the fiber type composition. During maximal exercise at 100% of VO2max or sustained isometric contractions to fatigue, about 15% of the adenine nucleotide (AN) pool is degraded through deamination of AMP to IMP. It is suggested that the stimulus for increased AMP deamination is increased transient levels of ADP and AMP in the contracting muscle fiber. Deamination of AMP to IMP and NH3 provides a sink for ADP, whereby the ATP/ADP ratio and the phosphorylation potential are kept high, which may be essential for the continuation of the contraction process. This implies that the relative levels of the adenine nucleotides are more important for maintenance of adequate cellular function than the absolute concentration of ATP.
Sahlin
K
K
Department of Clinical Physiology, Karolinska Institute, Huddinge University Hospital, Sweden.
Broberg
S
S
D000659:AMP Deaminase / Q000378:metabolism; D000227:Adenine Nucleotides / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D003641:Deamination; D004734:Energy Metabolism; D015444:Exercise / Q000502:physiology*; D006801:Humans; D009119:Muscle Contraction; D009132:Muscles / Q000201:enzymology / Q000378:metabolism*; D051381:Rats
D000227:Adenine Nucleotides; D000244:Adenosine Diphosphate; D000659:AMP Deaminase