Glutathione Metabolism and Its Implications for Health

Glutathione Metabolism and Its

Implications for Health

1

Guoyao Wu,

2

Yun-Zhong Fang,* Sheng Yang,

†

Joanne R. Lupton, and Nancy D. Turner

Faculty of Nutrition, Texas A&M University, College Station, TX,

77843; *Department of Biochemistry and Molecular Biology,

Beijing Institute of Radiation Medicine, Beijing, China 100850; and

†

Department of Animal Nutrition, China Agricultural University,

Beijing, China 100094

ABSTRACT

Glutathione (

-glutamyl-cysteinyl-glycine; GSH)

is the most abundant low-molecular-weight thiol, and GSH/

glutathione disulfide is the major redox couple in animal

cells. The synthesis of GSH from glutamate, cysteine, and

glycine is catalyzed sequentially by two cytosolic enzymes,

-glutamylcysteine synthetase and GSH synthetase. Com-

pelling evidence shows that GSH synthesis is regulated

primarily by

-glutamylcysteine synthetase activity, cys-

teine availability, and GSH feedback inhibition. Animal and

human studies demonstrate that adequate protein nutrition

is crucial for the maintenance of GSH homeostasis. In ad-

dition, enteral or parenteral cystine, methionine,

N

-acetyl-

cysteine, and

L

-2-oxothiazolidine-4-carboxylate are effec-

tive precursors of cysteine for tissue GSH synthesis.

Glutathione plays important roles in antioxidant defense,

nutrient metabolism, and regulation of cellular events (in-

cluding gene expression, DNA and protein synthesis, cell

proliferation and apoptosis, signal transduction, cytokine

production and immune response, and protein glutathiony-

lation). Glutathione deficiency contributes to oxidative

stress, which plays a key role in aging and the pathogene-

sis of many diseases (including kwashiorkor, seizure, Alz-

heimer’s disease, Parkinson’s disease, liver disease, cystic

fibrosis, sickle cell anemia, HIV, AIDS, cancer, heart attack,

stroke, and diabetes). New knowledge of the nutritional

regulation of GSH metabolism is critical for the develop-

ment of effective strategies to improve health and to treat

these diseases. J. Nutr. 134: 489 – 492, 2004

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