The ubiquitin-proteasome pathway: review of a novel intracellular mechanism of muscle protein breakdown during sepsis and other catabolic conditions.
BACKGROUND
Patients with sepsis and other catabolic conditions, such as severe trauma, cancer, and fasting, suffer significant loss of body protein, the majority of which originates from skeletal muscle. Recent evidence suggests that muscle protein breakdown during sepsis is caused by upregulated activity in the ubiquitin-proteasome pathway and is associated with increased expression of the ubiquitin gene.


OBJECTIVE
The purpose of the study was to review the role of the ubiquitin-proteasome pathway in the regulation of muscle proteolysis during sepsis and other catabolic conditions.


METHODS
Proteins that are degraded by the ubiquitin-proteasome mechanism are first conjugated to ubiquitin, a 76-amino-acid, highly conserved residue. Ubiquitinated proteins are recognized by the 26S proteasome, which is a large proteolytic complex consisting of the 19S cap complex and the 20S proteasome. The 20S proteasome is a cylindrical particle composed of four stacked rings, making it look like a barrel. The rings form a "tunnel" in which the target proteins are hydrolyzed, after which ubiquitin is released to be reused in the proteolytic pathway. A unique feature of the ubiquitin-proteasome proteolytic pathway is its energy dependency.


CONCLUSIONS
An understanding of the molecular regulation of protein metabolism in patients with sepsis and other catabolic conditions is important because it may form the basis for improved treatment in the future.
Hasselgren
P O
PO
Department of Surgery, University of Cincinnati, Ohio 45267-0558, USA.
Fischer
J E
JE
D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D012333:RNA, Messenger / Q000032:analysis; D018805:Sepsis / Q000378:metabolism*; D014157:Transcription Factors; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*
D009097:Multienzyme Complexes; D009124:Muscle Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D014452:Ubiquitins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex