Also known as

GH, gamma-glutamyl hydrolase, conjugase, folylpolygammaglutamyl carboxypeptidase

Overview

GGH (Gamma-Glutamyl Hydrolase) encodes a lysosomal enzyme that removes polyglutamate tails from folate coenzymes, converting them to monoglutamate forms that can be exported from cells or transported between tissues. This enzyme plays a critical role in folate homeostasis by regulating the cellular retention and distribution of folate vitamins.

GGH activity affects response to the antifolate drug methotrexate, which is used in cancer chemotherapy and autoimmune diseases. Higher GGH activity can reduce methotrexate effectiveness by decreasing its cellular retention. Variants in GGH have been associated with folate status, homocysteine levels, and neural tube defect risk, highlighting its importance in folate metabolism beyond drug response.

Understanding your GGH genetic status provides insights into folate handling and may be relevant for optimizing folate supplementation strategies. This information is also important for individuals receiving methotrexate therapy, as GGH activity can influence drug efficacy.

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