Abstract
Ornithine transcarbamylase (OTC; EC 2.1.3.3) is a ubiquitous enzyme found in almost all organisms, including vertebrates, microorganisms, and plants. Anabolic, mostly trimeric OTCs catalyze the production of L-citrulline from L-ornithine which is a part of the urea cycle. In eukaryotes, such OTC localizes to the mitochondrial matrix, partially bound to the mitochondrial inner membrane and part of channeling multi-enzyme assemblies. In mammals, mainly two organs express OTC: the liver, where it is an integral part of the urea cycle, and the intestine, where it synthesizes citrulline for export and plays a major role in amino acid homeostasis, particularly of L-glutamine and L-arginine. Here, we give an overview on OTC genes and proteins, their tissue distribution, regulation, and physiological function, emphasizing the importance of OTC and urea cycle enzymes for metabolic regulation in human health and disease. Finally, we summarize the current knowledge of OTC deficiency, a rare X-linked human genetic disorder, and its emerging role in various chronic pathologies.
Highlights
Ornithine transcarbamylase (OTC, EC 2.1.3.3; called ornithine carbamoyltransferase, OCT) is an evolutionary ancient enzyme, present in most organisms from bacteria to plants and vertebrates, and mostly encoded by a single nuclear gene
Anabolic OTCs catalyze the transfer a carbamoyl group from carbamoyl phosphate (CP) to the amino group of L-ornithine (ORN), yielding citrulline (CIT) and phosphate. This anabolic two-substrate reaction is involved in essential metabolic pathways such as the biosynthesis of citrulline and arginine, ammonia homeostasis, and the urea cycle in mammals (Figure 1)
OTCs are localized in the mitochondrial matrix space (Takiguchi et al, 1989) where they assemble into homotrimers as basic catalytic unit (Shi et al, 1998)
Summary
Ornithine transcarbamylase (OTC, EC 2.1.3.3; called ornithine carbamoyltransferase, OCT) is an evolutionary ancient enzyme, present in most organisms from bacteria to plants and vertebrates, and mostly encoded by a single nuclear gene. Anabolic OTCs catalyze the transfer a carbamoyl group from carbamoyl phosphate (CP) to the amino group of L-ornithine (ORN), yielding citrulline (CIT) and phosphate This anabolic two-substrate reaction is involved in essential metabolic pathways such as the biosynthesis of citrulline and arginine, ammonia homeostasis, and the urea cycle in mammals (Figure 1). OTCs are localized in the mitochondrial matrix space (Takiguchi et al, 1989) where they assemble into homotrimers (or oligomers thereof) as basic catalytic unit (Shi et al, 1998) These anabolic OTCs differ from catabolic OTCs that promote the reverse reaction and are only found in lower microorganisms that use arginine as a carbon source for ATP generation. The CIT generated here is entirely channeled into the urea
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