Biochemical mechanisms of cellular catabolism.
OBJECTIVE
To provide an in-depth analysis of current developments concerning biochemical mechanisms of cellular catabolism. There have been a number of important developments in this area over the past 12 months, particularly with respect to protein catabolism.


RESULTS
Protein degradation in a range of catabolic conditions is mediated primarily through the ubiquitin-proteasome proteolytic pathway. Glucocorticoids have been suggested to activate this system in sepsis, while in cancer cachexia a tumour-produced sulphated glycoprotein, proteolysis-inducing factor, induces protein catabolism in skeletal muscle by increasing expression of proteasome subunits and the ubiquitin carrier protein, E2(14k). Apoptosis may also be important in the loss of muscle protein during the early stage of cachexia. Induction of proteasome expression by glucocorticoids appears to be a direct result of the downregulation of the activity of nuclear factor kappaB, while proteolysis-inducing factor acts through 15-hydroxyeicosatetraenoic acid as an intracellular transducer.


CONCLUSIONS
Formation of 15-hydroxyeicosatetraenoic acid is inhibited by eicosapentaenoic acid, which has been shown to attenuate the development of weight loss in patients with pancreatic cancer. When eicosapentaenoic acid is combined with an energy dense nutritional supplement, there is an increase in body weight of cachectic cancer patients through an increase in lean body mass. Eicosapentaenoic acid also prevents protein catabolism and activation of the ubiquitin-proteasome proteolytic pathway during acute starvation in mice, suggesting a similar pathway is involved. Thus eicosapentaenoic acid may be effective in the treatment of protein catabolism in conditions other than cancer.
Tisdale
Michael J
MJ
Pharmaceutical Sciences Research Institute, Aston University, Birmingham, UK. m.j.tisdale@aston.ac.uk
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001798:Blood Proteins / Q000378:metabolism*; D002477:Cells / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011509:Proteoglycans; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism*; D019282:Wasting Syndrome / Q000378:metabolism*
D001798:Blood Proteins; D009097:Multienzyme Complexes; D009124:Muscle Proteins; D011509:Proteoglycans; D014157:Transcription Factors; C042057:proteolysis-inducing peptide; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex