Academic journal article Alcohol Research

Intracellular Proteolytic Systems in Alcohol-Induced Tissue Injury

Academic journal article Alcohol Research

Intracellular Proteolytic Systems in Alcohol-Induced Tissue Injury

Article excerpt

The body constantly produces proteins and degrades proteins that are no longer needed or are defective. The process of protein breakdown, called proteolysis, is essential to cell survival. Numerous proteolytic systems exist in mammalian cells, the most important of which are the lysosomes, the ubiquitin-proteasome pathway, and enzymes called calpains. Lysosomes are small cell components that contain specific enzymes (i.e., proteases) which break down proteins. Alcohol interferes with the formation and activity of lysosomes and thus may contribute to protein accumulation in the liver, which can have harmful effects on that organ. In the ubiquitin-proteasome pathway, proteins that are to be degraded are first marked by the addition of ubiquitin molecules and then broken down by large protein complexes called proteasomes. Alcohol impairs this proteolytic system through several mechanisms, possibly leading to inflammation and even cell death. Calpains are proteases that are involved in several physiological processes, including the breakdown of proteins that give cells their shape and stability. In contrast to the lysosomal and ubiquitin-proteasome systems, calpains in brain cells are activated by alcohol, to potentially detrimental effect. KEY WORDS: ethanol metabolism; protein metabolism disorder; biochemical reaction property; tissue; injury; inflammation; alcohol dehydrogenases; cytochrome P450 2E1; AODR (alcohol and other drug related) injury; proteolysis; protease inhibitors; cytolysis; apoptosis; lysosome; coenzymes; physiological AODE (alcohol and other drug effects); ubiquitin-proteasome system

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In all cells, the production and degradation of proteins, commonly known as protein turnover, is a constant, ongoing process that is crucial for tissue renewal. A well-nourished person synthesizes nearly 1 pound of protein per day. This protein gain is balanced by an equal amount of proteins that are broken down into their building blocks, the amino acids. This cycle of protein turnover is a necessary component of cell survival and repair because it ensures that damaged proteins are degraded and that all proteins needed by the cells for a variety of functions are available at the right time and in the right amounts.

Compared with the intense interest of researchers in protein synthesis, protein degradation--also known as protein catabolism or proteolysis--was for years considered a backwater area of scientific investigation. This neglect resulted largely from the assumption that, in contrast to the relative complexity of protein synthesis, protein degradation consisted of a random array of biochemical reactions that were facilitated (i.e., catalyzed) by certain enzymes and only involved breaking apart the chemical peptide bonds that hold amino acids together. Research over the last 30 years has revealed, however, that protein degradation occurs in a highly coordinated, specific manner through multiple systems which rival the complexity of protein synthesis. Moreover, all protein degradation systems are tightly regulated in order to maintain a "steady state" level of intracellular proteins. If this steady state is disrupted by metabolic disturbances, by the presence of surplus reactive molecules such as free radicals, or by toxic agents such as alcohol, cell injury and sometimes cell death can occur (Mehlhase and Grune 2002).

This article describes the significance of protein degradation for cell metabolism, introduces the major systems involved in this process, and explores ways in which alcohol consumption can disrupt protein catabolism, thereby bringing about tissue injury in the liver as well as other organs.

THE METABOLIC IMPORTANCE OF PROTEIN DEGRADATION

Proteins are degraded by a type of chemical reaction known as hydrolysis--a simple reaction in which a protein is "cut" at one or more peptide bonds by the addition of water, either to generate smaller protein fragments (i. …

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