Untargeted NMR Metabolomics Reveals Alternative Biomarkers and Pathways in Alkaptonuria.

ABSTRACT: Alkaptonuria (AKU) is an ultra-rare metabolic disease caused by the accumulation of homogentisic acid (HGA), an intermediate product of phenylalanine and tyrosine degradation. AKU patients carry variants within the gene coding for homogentisate-1,2-dioxygenase (HGD), which are responsible for reducing the enzyme catalytic activity and the consequent accumulation of HGA and formation of a dark pigment called the ochronotic pigment. In individuals with alkaptonuria, ochronotic pigmentation of connective tissues occurs, leading to inflammation, degeneration, and eventually osteoarthritis. The molecular mechanisms underlying the multisystemic development of the disease severity are still not fully understood and are mostly limited to the metabolic pathway segment involving HGA. In this view, u

SUBMITTER: Grasso D 

PROVIDER: S-EPMC9779518 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature