cachexia
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Cori cycle with sources of gluconeogenic substrates
Tumours produce factors such as lipid-mobilizing factor (LMF), which induces breakdown of adipose tissue into fatty acids, and proteolysis-inducing factor (PIF), which induces protein degradation (amino acids) in skeletal muscle. Tumour necrosis factor (TNF)- also contributes to these processes.
These are important gluconeogenic substrates that can be used in acute-phase protein (APP) synthesis by the liver. Tumours convert glucose to lactate, which is transferred to the liver, where it is converted back into glucose. This cycle uses a large amount of energy, and might contribute to cachexia.
Protein levels in muscle
Protein levels in muscle are determined by the amount of dietary intake of protein and levels of protein synthesis. Decreases in plasma insulin concentrations or insulin sensitivity of skeletal muscle can activate three main proteolytic pathways that underlie protein catabolism in skeletal muscle.
These are the lysosomal system, which proteolyses extracellular proteins and cell-surface receptors; the cytosolic calcium-activated system, which involves calpains I and II and is involved in tissue injury, necrosis and autolysis, and the ATP-ubiquitin-dependent proteolytic pathway.
This proteolysis leads to hepatic production of acute-phase protein (APP), which can limit the availability of certain amino acids for protein synthesis in skeletal muscle. Protein deamination also leads to nitrogen excretion, producing a negative nitrogen balance, and glucose production, which increases muscle activity.
References
Cachexia in cancer patients. Michael J. Tisdale. Nature Reviews Cancer 2, 862-871 (November 2002)