Deciphering the role of ammonia in MASLD: From a neurotoxin to a metabolic by-product

This is the authors' abstract. We don't add key points for this paper.

Ammonia, a nitrogen-containing compound produced during amino acid catabolism, plays a key role in nitrogen homeostasis. The primary source of ammonia in humans is the gut, where it is produced from dietary sources, luminal bacterial urease activity and glutamine deamination in enterocytes.1 This gut-derived ammonia is transported to the liver via the portal vein, and because ammonia is potentially neurotoxic, rapid and efficient removal is essential. Among others organs, the liver is the main organ responsible for its detoxification via the urea cycle. Ureagenesis occurs specifically in periportal hepatocytes by the action of urea cycle enzymes (UCEs), which involves two mitochondrial enzymes (carbamoyl phosphate synthetase 1 (CPS1) and ornithine transcarbamylase (OTC)) and three cytosolic enzymes (arginosuccinate synthetase (ASS), arginosuccinate lyase (ASL) and arginase 1 (ARG1)). In health, ammonia is converted into urea, which is excreted by the kidneys maintaining the systemic nitrogen balance