Hepatic protein turnover is highly regulated, which allows the activity of metabolic pathways to adapt to alterations in physiologic circumstances. Mammalian cells possess several proteolytic systems. Plasma proteins and membrane receptors are endocytosed, to be hydrolyzed by acid proteases within intracellular organelles known as lysosomes; intracellular proteins are degraded within structures known as proteasomes. These are large protein complexes that are present in the cytosol. Each proteasome which consists of four rings of protein subunits, the rings being stacked on top of one another to form a hollow cylindrical structure within which the intracellular proteins are hydrolyzed to small peptides of six to 12 amino acids . These peptides are released into the cytoplasm, where they are further degraded to their constituent amino acids by peptidases.
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| The intracellular proteins intended for proteasomal degradation are marked by conjugation with a small protein, ubiquitin
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| Ubiquitin is coupled to the amino groups of protein lysyl residues, and this conjugation reaction is repeated to form chains of five or more ubiquitin molecules linked to the protein. Ubiquitin-bound proteins are targeted for degradation. The specificity of the proteasomal degradation relies on the specificity of the enzymes responsible for the ligation of ubiquitin to the protein substrate, without which the protein will not enter the proteasome.
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