🎓Disorders of Human Valine Catabolism – Key Metabolites and Pathomechanisms

Valine is an essential amino acid that the body breaks down to produce energy. This breakdown happens in several steps, each involving specific enzymes. If these enzymes do not function properly, certain byproducts can build up. One such metabolite is 3-hydroxyisobutyrate (HIB), which may accumulate due to variations in two genes, HIBADH (encodes 3-Hydroxyisobutyrate dehydrogenase) and ALDH6A1 (encodes Methylmalonate semialdehyde dehydrogenase), that have been linked to rare inherited metabolic conditions, but their exact impact on health is still unclear. Only a few patients with these gene defects have been reported, showing a wide range of symptoms. This makes it difficult to know whether these changes cause disease or are harmless. My research will study roles of HIBADH and ALDH6A1 and which effects HIB may exert in human-derived cellular systems and animals (nematode C. elegans).