Glyceroneogenic

Glyceroneogenic is an adjective relating to glyceroneogenesis, a metabolic pathway that generates glycerol-3-phosphate for triglyceride synthesis from non-glycerol substrates. This pathway functions as a branch of gluconeogenesis and is particularly important in tissues with limited glycerol kinase activity, such as adipose tissue, where it provides the glycerol-3-phosphate backbone needed to re-esterify fatty acids released during lipolysis.

The glyceroneogenic pathway uses substrates such as lactate, pyruvate, and amino acids like alanine to form glycerol-3-phosphate through a sequence that mirrors parts of gluconeogenesis. In brief, pyruvate is converted to oxaloacetate in the mitochondria, which is then shuttled to the cytosol as malate. Oxaloacetate is converted to phosphoenolpyruvate by PEP carboxykinase, and the carbon skeletons are ultimately rearranged to form dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate. DHAP is reduced by glycerol-3-phosphate dehydrogenase to glycerol-3-phosphate, which serves as the glycerol backbone for triglyceride assembly alongside fatty acyl-CoA.

Regulation of glyceroneogenesis involves hormonal and metabolic signals. Glucagon and catecholamines stimulate the process through induction of key gluconeogenic enzymes, notably PEPCK, while insulin generally inhibits it. The pathway supports triglyceride synthesis during fasting or energy surplus, facilitating re-esterification of fatty acids and contributing to lipid transport in the form of very-low-density lipoproteins in the liver.

In health and disease, glyceroneogenesis is studied for its role in lipid homeostasis and its potential involvement in metabolic disorders such as obesity and insulin resistance, where altered triglyceride flux can impact plasma lipid levels.