The metabolic importance of the glutaminase II pathway in normal and cancerous cells.
Anal Biochem
; 644: 114083, 2022 05 01.
Article
em En
| MEDLINE
| ID: mdl-33352190
ABSTRACT
In rapidly dividing cells, including many cancer cells, l-glutamine is a major energy source. Utilization of glutamine is usually depicted as l-glutamine â l-glutamate (catalyzed by glutaminase isozymes; GLS1 and GLS2), followed by l-glutamate â α-ketoglutarate [catalyzed by glutamate-linked aminotransferases or by glutamate dehydrogenase (GDH)]. α-Ketoglutarate is a major anaplerotic component of the tricarboxylic acid (TCA) cycle. However, the glutaminase II pathway also converts l-glutamine to α-ketoglutarate. This pathway consists of a glutamine transaminase coupled to ω-amidase [Net reaction l-Glutamine + α-keto acid + H2O â α-ketoglutarate + l-amino acid + NH4+]. This review focuses on the biological importance of the glutaminase II pathway, especially in relation to metabolism of cancer cells. Our studies suggest a component enzyme of the glutaminase II pathway, ω-amidase, is utilized by tumor cells to provide anaplerotic carbon. Inhibitors of GLS1 are currently in clinical trials as anti-cancer agents. However, this treatment will not prevent the glutaminase II pathway from providing anaplerotic carbon derived from glutamine. Specific inhibitors of ω-amidase, perhaps in combination with a GLS1 inhibitor, may provide greater therapeutic efficacy.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glutamina
/
Ácidos Cetoglutáricos
Idioma:
En
Revista:
Anal Biochem
Ano de publicação:
2022
Tipo de documento:
Article