Citrulline: From metabolism to therapeutic use

Abstract

Citrulline possesses a highly specific metabolism that bypasses splanchnic extraction because it is not used by the intestine or taken up by the liver. The administration of citrulline may be used to deliver available nitrogen for protein homeostasis in peripheral tissues and as an arginine precursor synthesized de novo in the kidneys and endothelial and immune cells. Fresh research has shown that citrulline is efficiently transported across the intestinal luminal membrane by a set of transporters belonging to the B⁰,⁺, L, and b⁰,⁺ systems. Several pharmacokinetic studies have confirmed that citrulline is efficiently absorbed when administered orally. Oral citrulline could be used to deliver arginine to the systemic circulation or as a protein anabolic agent in specific clinical situations, because recent data have suggested that citrulline, although not a component of proteins, stimulates protein synthesis in skeletal muscle through the mammalian target of rapamycin signaling pathway. Hence, citrulline could play a pivotal role in maintaining protein homeostasis and is a promising pharmaconutrient in nutritional support strategies for malnourished patients, especially in aging and sarcopenia.

Immunosuppressive Effects of Arginine Deiminase From Streptococcus Pyogenes

“…Эукариотические клетки, которые экспрессируют ферменты цикла мочевой кислоты -АСС и АСЛ и транспортеры этой аминокислоты, способны ресинтезировать аргинин из цитрулина. Хотя АСС и АСЛ обна-руживаются во всех тканях, высокий уровень их экспрессии характерен только для клеток печени и почек [3]. В эндотелиальных клетках и макро-фагах оба фермента вместе с NOS являются ча-стью цикла NO-цитрулин, в котором цитрулин конвертируется в аргинин с последующей гене-рацией NO [33].…”

Enhanced L-citrulline in parboiled paddy rice with watermelon (Citrullus lanatus) juice for preventing Sarcopenia: A preliminary study

“…Unlike other amino acids, L-citrulline possesses a highly specific metabolism that bypasses splanchnic (internal organ) extraction. Because L-citrulline is not used by the intestine or taken up by the liver, it is made available throughout the body rapidly after ingestion and thus may act directly (Bahri et al, 2013). L-citrulline is a non protein amino acid that is produced predominantly in the intestines (Betue et al, 2013) and metabolized to L-arginine in the vascular endothelium, renal and other cells.…”

“…L-citrulline increases the blood concentration of L-arginine more effectively than oral L-arginine, as L-citrulline undergoes neither intestinal nor hepatic metabolism, is not a substrate for arginase, and does not induce the expression or activity of the enzyme (Orozco-Gutiérrez et al, 2010). Using L-citrulline to combat sarcopenia has been assessed in clinical trials with promising results (Bahri et al, 2013;Moinard and Cynober, 2007) and plays a key role in the immune system (Yu et al, 1995).…”

“…Several pharmacokinetic studies have confirmed that Lcitrulline is efficiently absorbed when administered orally (Bahri et al, 2013). Oral L-citrulline supplements, readily available in industrialized countries, could be used to deliver L-arginine to the systemic circulation or as a protein anabolic agent in specific clinical situations for sarcopenia (Bahri et al, 2013).…”

“…Oral L-citrulline supplements, readily available in industrialized countries, could be used to deliver L-arginine to the systemic circulation or as a protein anabolic agent in specific clinical situations for sarcopenia (Bahri et al, 2013). Although L-citrulline represents an interesting nutritional strategy, delivery in the African sub-Saharan countries faces constraints of poverty, poor access to pharmaceutical supplements and lack of adequate medical care.…”