Almost all about citrulline in mammals

Area of Science:

• Biochemistry
• Physiology
• Pathology

Background:

• Citrulline (Cit) is a vital amino acid closely linked to arginine metabolism in mammals.
• Mammalian citrulline metabolism encompasses both free citrulline and protein citrullination.
• Key enzymes like nitric oxide synthase (NOS), ornithine carbamoyltransferase (OCT), and argininosuccinate synthetase (ASS) regulate citrulline pathways.

Purpose of the Study:

• To elucidate the distinct metabolic pathways of citrulline in mammals.
• To explore the potential of citrulline in monitoring and treating various pathologies.
• To highlight citrulline as a potential therapeutic alternative to arginine.

Main Methods:

• Analysis of citrulline's enzymatic synthesis and conversion pathways.
• Examination of tissue-specific enzyme distribution defining metabolic routes.
• Review of existing literature on citrulline's therapeutic applications and disease associations.

Main Results:

• Identified three distinct metabolic pathways for citrulline: hepatic urea production, arginine recycling for NO synthesis, and kidney conversion of circulating citrulline to arginine.
• Highlighted pathologies linked to each pathway, including urea cycle disorders and autoimmune diseases.
• Demonstrated citrulline's potential as a marker for short bowel function and as an alternative to arginine supplementation.

Conclusions:

• Citrulline metabolism is compartmentalized into distinct pathways with significant physiological and pathological implications.
• Citrulline holds promise as a therapeutic agent for urea cycle disorders, NO modulation, and potentially other conditions.
• Circulating citrulline serves as a viable precursor to arginine, bypassing hepatic metabolism.