[ncbi.nlm.nih.gov]

GSH = glutathione
N-acetylcysteine (NAC) = cysteine supplement
ROS = Reactive Oxygen Species
SAA = Sulfur Amino Acid

In its best-known role, GSH participates in enzyme-mediated reactions to neutralize ROS, preventing the accumulation of ROS damage to DNA, proteins, and lipids. Glutathione peroxidases play a key role in this process by catalyzing the reaction of GSH with peroxides, including hydrogen peroxide and lipid peroxides. Thus, decreasing GSH can sharply augment oxidative damage and result in cell death or loss of function.

given the diverse roles that GSH plays in cellular physiology and regulation of enzyme activity and protein function, the consequences of low GSH levels have mainly been discussed from a clinical perspective in terms of the loss of protection against intracellular oxidative stress. However, while antioxidants such as vitamins E and C can spare GSH under conditions of oxidative stress, GSH loss can only be offset by GSH resynthesis

Synthesis of GSH requires cysteine, a conditionally essential amino acid that must be obtained from dietary sources or by conversion of dietary methionine via the cystathionase pathway. If the supply of cysteine is adequate, normal GSH levels are maintained. In contrast, if supplies of cysteine are inadequate to maintain GSH homeostasis in the face of increased GSH consumption, GSH depletion occurs.

GSH depletion impacts a wide variety of cellular processes, ranging from DNA synthesis and gene expression to sugar metabolism and lactate production.

Acute GSH depletion causes severe—often fatal—oxidative and/or alkylation injury. This injury can be prevented by rapid treatment with NAC, an efficient nontoxic source of cysteine

Chronic over-consumption of alcohol is well known to deplete GSH in certain tissues, particularly the liver, and thus to render patients susceptible to APAP toxicity at doses well below those that cause toxicity in healthy individuals.

Since mammals obtain cysteine both directly from the diet and by degradation of dietary methionine, the normal cysteine requirement can be satisfied from dietary sources. However, as indicated above, an additional source of cysteine may be required when cysteine loss (e.g., via GSH loss) outstrips the usual dietary supply.

poor appetite and/or a tendency to select fresh food with low SAA content or bioavailability (Hitchins et al. 1989) or processed food depleted of SAAs (Volkin and Klibanov 1987; Schnackenberg et al. 2009; Briganti et al. 2008) can result in cysteine deficiency even in otherwise healthy people. Furthermore, as evidence here indicates, the need for SAAs can be substantially increased in many disease states.

The human liver does contain a reservoir of cysteine (about 1 g) that is largely present in GSH. Since this amount approximates the daily SAA requirement, it provides only a short-term source to maintain a stable cysteine supply despite intermittent methionine and cysteine consumption. Under conditions of excessive cysteine requirements or deficient cysteine/methionine consumption, GSH is released from skeletal muscle and other tissues to supply cysteine. This results in decreased antioxidant and detoxification functions throughout the body.

GSH has been shown to regulate or influence the expression of several genes, notably inflammatory genes

GSH regulates the activity of enzymes and other intracellular molecules by posttranslational modifications (glutathionylations) that control the oxidation state of protein-SH groups.

Decreasing GSH increases the intracellular redox potential of the GSH/GSSG redox couple and puts an additional burden on the Trx-Trx reductase system. This may be quite important in patients who have low selenium levels

the modest malnutrition common in elderly people, who also frequently have low GSH levels (Anderson et al. 1993, 2001), puts the elderly at risk for developing clinically significant cysteine/GSH deficiency and hence at increased risk of hepatic and other tissue injuries

A role for GSH deficiency in the clinical manifestations of a broad spectrum of in diseases and conditions that include systemic inflammatory response syndrome (SIRS), acute respiratory distress syndrome (ARDS), chronic lung disease (CLD), chronic obstructive pulmonary disease (COPD), neurodegenerative disease, cardiovascular disease, alcoholism, infectious disease (e.g., HIV-1 infection and chronic hepatitis), hepatic and renal failure, diabetes, malnutrition, and certain autoimmune diseases.



Edited 1 time(s). Last edit at 08/23/2022 10:20PM by Panchito.