25 November 2024

Glutamine may have a key role in the treatment of red blood cell disorders such as sickle cell disease and β-thalassaemia, according to a new study.

Researchers at St Jude’s Children’s Research Hospital, Tennessee, USA, say their findings, reported in Science, help explain the working of some drugs already in use for red blood cell diseases.

According to their findings, glutamine is broken down in the early stages of red blood cell development – but later the cells switch and begin to synthesise it. At this point, the cells begin producing glutamine synthetase, an enzyme which uses ammonium to produce glutamine. The objective, they believe, is to manage levels of ammonium, a by-product of heme production.

According to the study, there is a deficiency of glutamine synthetase in β-thalassaemia. The researchers found that the drug luspatercept increases ratios of glutamine to glutamate, suggesting it helps recover glutamine levels.

They point out that L-glutamine is used as a drug to alleviate symptoms of sickle cell disease, but the mechanism of action was not clear. This study sheds some light on how L-glutamine and luspatercept work to improve red blood cell disorders.

Researcher Dr Jian Xu said: “We noted a very surprising finding regarding glutamine, which is usually broken down by stem cells for various metabolic needs. We found that this process is completely reversed during later differentiation. The cells stop breaking down glutamine and begin to synthesise it by completely reversing the reaction.”

Dr Xu added: “We show this process is impaired in various red blood cell disorders, such as beta-thalassemia. This causes a metabolic phenotype that resembles a glutamine synthetase deficiency, which can be characterised by increased glutamate and ammonia levels and decreased glutamine levels.”

Source:

Lyu J, Gu Z, Zhang Y, Vu HS, Lechauve C, Cai F, Cao H, Keith J, Brancaleoni V, Granata F, Motta I, Cappellini MD, Huang LJ, DeBerardinis RJ, Weiss MJ, Ni M, Xu J. (2024) “A glutamine metabolic switch supports erythropoiesis.” Science, 15 November 2024, doi: 10.1126/science.adh9215.

Link: https://www.science.org/doi/10.1126/science.adh9215

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