Methylmalonic acid in aging and disease

• Published in: Trends in endocrinology and metabolism Vol. 35; no. 3; pp. 188 - 200
• Main Authors: Tejero, Joanne, Lazure, Felicia, Gomes, Ana P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.03.2024
• Subjects: aging; disease; metabolism; methylmalonic acid; methylmalonic acid; metabolism; disease; aging
• ISSN: 1043-2760; 1879-3061
• DOI: 10.1016/j.tem.2023.11.001

Methylmalonic acid (MMA) is a byproduct of propionate metabolism linked to vitamin B12 deficiency.MMA alters cellular metabolism through direct regulation of metabolic enzymes.MMA activates succinate receptor 1 and drives inflammation.MMA acts as a signaling molecule through methylmalonylation of proteins.MMA is linked to the development of several age-related chronic disorders. Metabolic byproducts have conventionally been disregarded as waste products without functions. In this opinion article, we bring to light the multifaceted role of methylmalonic acid (MMA), a byproduct of the propionate metabolism pathway mostly commonly known as a clinical biomarker of vitamin B12 deficiency. MMA is normally present at low levels in the body, but increased levels can come from different sources, such as vitamin B12 deficiency, genetic mutations in enzymes related to the propionate pathway, the gut microbiota, and aggressive cancers. Here, we describe the diverse metabolic and signaling functions of MMA and discuss the consequences of increased MMA levels, such as during the aging process, for several age-related human pathologies. Metabolic byproducts have conventionally been disregarded as waste products without functions. In this opinion article, we bring to light the multifaceted role of methylmalonic acid (MMA), a byproduct of the propionate metabolism pathway mostly commonly known as a clinical biomarker of vitamin B12 deficiency. MMA is normally present at low levels in the body, but increased levels can come from different sources, such as vitamin B12 deficiency, genetic mutations in enzymes related to the propionate pathway, the gut microbiota, and aggressive cancers. Here, we describe the diverse metabolic and signaling functions of MMA and discuss the consequences of increased MMA levels, such as during the aging process, for several age-related human pathologies.