Citrulline production and protein homeostasis

Ginguay, Antonin; Bandt, Jean‐Pascal De

doi:10.1097/mco.0000000000000585

Cited by 13 publications

(6 citation statements)

References 37 publications

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“…This is the first report to show alterations in citrulline levels that could be attributed to ICSI procedures. Citrulline can originate from ornithine by actions of the ornithine carbamyl/carbamoyl transferase (OTC) or be released as by-product resulted from enzymatic nitric oxide synthesis from arginine by endothelial nitric oxide synthase (eNOS), inflammatory (iNOS) or neuronal NOS (nNOS) [ 45 , 46 , 47 ]. Of interest, placental citrulline synthesis and transport is not well understood, but may occur via distinct transporter systems as reported in other cell types [ 44 , 46 ].…”

Section: Discussionmentioning

confidence: 99%

“…Enterocytes may uptake citrulline using B (0,+), L, and b (0,+) amino acid transport systems [ 48 ], whereas in human umbilical vein cells (HUVECs), citrulline, along with arginine, is transported via the cationic amino acid transporter system y+/CATs [ 49 ]. Citrulline transmembrane transport occurring via Na+-dependent systems in rat small intestine and proximal tubular kidney cells have also been documented [ 47 , 50 , 51 ]. Of importance, citrulline levels in fetal plasma were increased in nutrient restricted (70% of control diet) pregnant baboons at mid-pregnancy, with no alterations in fetal and placental weight, i.e., prior to the onset of IUGR [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

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Altered Umbilical Cord Blood Nutrient Levels, Placental Cell Turnover and Transporter Expression in Human Term Pregnancies Conceived by Intracytoplasmic Sperm Injection (ICSI)

et al. 2021

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Assisted reproductive technologies (ART) may increase risk for abnormal placental development, preterm delivery and low birthweight. We investigated placental morphology, transporter expression and paired maternal/umbilical fasting blood nutrient levels in human term pregnancies conceived naturally (n = 10) or by intracytoplasmic sperm injection (ICSI; n = 11). Maternal and umbilical vein blood from singleton term (>37 weeks) C-section pregnancies were assessed for levels of free amino acids, glucose, free fatty acids (FFA), cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), very low-density lipoprotein (VLDL) and triglycerides. We quantified placental expression of GLUT1 (glucose), SNAT2 (amino acids), P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) (drug) transporters, and placental morphology and pathology. Following ICSI, placental SNAT2 protein expression was downregulated and umbilical cord blood levels of citrulline were increased, while FFA levels were decreased at term (p < 0.05). Placental proliferation and apoptotic rates were increased in ICSI placentae (p < 0.05). No changes in maternal blood nutrient levels, placental GLUT1, P-gp and BCRP expression, or placental histopathology were observed. In term pregnancies, ICSI impairs placental SNAT2 transporter expression and cell turnover, and alters umbilical vein levels of specific nutrients without changing placental morphology. These may represent mechanisms through which ICSI impacts pregnancy outcomes and programs disease risk trajectories in offspring across the life course.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Altered Umbilical Cord Blood Nutrient Levels, Placental Cell Turnover and Transporter Expression in Human Term Pregnancies Conceived by Intracytoplasmic Sperm Injection (ICSI)

et al. 2021

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“…Large amounts of NO program macrophages to a cytotoxic type, which produce NO and RNS to eliminate intracellular bacteria and parasites [38]. Smaller amounts of NO can shift the function of macrophages to tissue repair [39]. Macrophage-secreted NO also influences matrix metalloproteinases (MMPs) with concentration-dependent (in)activation [40].…”

Section: Restoring Nitric Oxide Production: Reinforcement Of Host Def...mentioning

confidence: 99%

NO, way to go: critical amino acids to replenish nitric oxide production in treating mucositis

Molendijk¹,

Blijlevens²

2021

Current Opinion in Supportive &Amp; Palliative Care

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Purpose of reviewThere is still an unmet need for preventive and treatment strategies for chemotherapy-induced and radiotherapy-induced mucositis and its associated systemic inflammatory response (SIR) in cancer patients. Because of citrulline depletion due to cytotoxic therapy, nitric oxide (NO) production can be reduced, limiting its effect in many physiological processes. Restoring NO production could relieve mucositis severity by supporting host damage control mechanisms. Amino acids glutamine, arginine and citrulline are involved in NO production. This review including recent literature of preclinical and clinical studies will discuss the potential benefits of glutamine, arginine and citrulline on mucositis development with focus on NO production.Recent findingsMucositis severity is more defined by host response to DNA damage than by DMA damage itself. Citrulline depletion because of afunctional enterocytes could be responsible for NO depletion during cytotoxic therapy. Restoring NO production during cytotoxic therapy could have a beneficial effect on mucositis development. Citrulline seems a more promising NO donor than glutamine or arginine during cytotoxic therapy, although clinical studies in mucositis patients are currently lacking.SummaryGlutamine, arginine and citrulline show in-vitro beneficial effects on inflammatory processes involved in mucositis. Translation to the clinic is difficult as demonstrated with use of glutamine and arginine. Citrulline, being the most potent NO donor with excellent oral bio-availability, is very promising as treatment choice for mucositis and its use deserves to be investigated in clinical trials with mucositis patients.

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“…7 It is postulated that CPS1 and OTC are highly expressed in the intestine and that deficiency results from the lack of intestinal citrulline production, leading to low plasma citrulline levels. 8 Though dietary citrulline can be absorbed by the intestine, it is not an essential amino acid in physiological conditions. There is no significant extra intestinal source of circulating citrulline.…”

Section: Introductionmentioning

confidence: 99%

Impact of citrulline substitution on clinical outcome after liver transplantation in carbamoyl phosphate synthetase 1 and ornithine transcarbamylase deficiency

Aldrian,

Waldner,

Vogel

et al. 2024

J of Inher Metab Disea

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Carbamoyl phosphate synthetase 1 (CPS1) and ornithine transcarbamylase (OTC) deficiencies are rare urea cycle disorders, which can lead to life‐threatening hyperammonemia. Liver transplantation (LT) provides a cure and offers an alternative to medical treatment and life‐long dietary restrictions with permanent impending risk of hyperammonemia. Nevertheless, in most patients, metabolic aberrations persist after LT, especially low plasma citrulline levels, with questionable clinical impact. So far, little is known about these alterations and there is no consensus, whether l‐citrulline substitution after LT improves patients' symptoms and outcomes. In this multicentre, retrospective, observational study of 24 patients who underwent LT for CPS1 (n = 11) or OTC (n = 13) deficiency, 25% did not receive l‐citrulline or arginine substitution. Correlation analysis revealed no correlation between substitution dosage and citrulline levels (CPS1, p = 0.8 and OTC, p = 1). Arginine levels after liver transplantation were normal after LT independent of citrulline substitution. Native liver survival had no impact on mental impairment (p = 0.67). Regression analysis showed no correlation between l‐citrulline substitution and failure to thrive (p = 0.611) or neurological outcome (p = 0.701). Peak ammonia had a significant effect on mental impairment (p = 0.017). Peak plasma ammonia levels correlate with mental impairment after LT in CPS1 and OTC deficiency. Growth and intellectual impairment after LT are not significantly associated with l‐citrulline substitution.

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Citrulline production and protein homeostasis

Cited by 13 publications

References 37 publications

Altered Umbilical Cord Blood Nutrient Levels, Placental Cell Turnover and Transporter Expression in Human Term Pregnancies Conceived by Intracytoplasmic Sperm Injection (ICSI)

Altered Umbilical Cord Blood Nutrient Levels, Placental Cell Turnover and Transporter Expression in Human Term Pregnancies Conceived by Intracytoplasmic Sperm Injection (ICSI)

NO, way to go: critical amino acids to replenish nitric oxide production in treating mucositis

Impact of citrulline substitution on clinical outcome after liver transplantation in carbamoyl phosphate synthetase 1 and ornithine transcarbamylase deficiency

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