Enzymological evidence for the indispensability of small intestine in the synthesis of arginine from glutamate

Wakabayashi, Yasuo; Iwashima, Akio; Yamada, Etsuko; Yamada, Ryohei

doi:10.1016/0003-9861(91)90098-4

Cited by 43 publications

(39 citation statements)

References 21 publications

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“…Since the plasma citrulline level is highly dependent on the small bowel epithelial cell mass, 36 loss of small intestinal enterocytes will decrease plasma citrulline levels. Citrulline values were compared in four groups of animals, receiving either syngeneic or allogeneic BM and splenocytes, combined with either PBS or KGF treatment.…”

Section: Kgf Decreases Injury To the Gastrointestinal Tractmentioning

confidence: 99%

Keratinocyte growth factor ameliorates acute graft-versus-host disease in a novel nonmyeloablative haploidentical transplantation model

Vanclée

Lutgens

Oving

et al. 2005

Bone Marrow Transplant

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Summary:Allogeneic stem cell transplantations (SCT) are currently being used as a therapy for hematological malignancies, some solid tumors and nonmalignant bone marrow deficiencies. Nevertheless, clinical applicability is limited due to toxicity of conditioning regimens, graft-versus-host disease (GVHD) and the scarcity of HLA-identical family donors. New concepts are based on nonmyeloablative conditioning to reduce toxicity, prevention or amelioration of GVHD and the use of haploidentical donors to increase donor availability. To combine these requirements, we have developed a nonmyeloablative conditioning regimen, consisting of low-dose total body irradiation and cyclophosphamide-based chemotherapy. In a haploidentical F1-F1 mouse model, this nonmyeloablative transplantation protocol resulted in stable full donor chimerism, but also in the development of severe GVHD. Administration of keratinocyte growth factor (KGF) reduced GVHD, evident as reduced weight loss and a lesser degree of dermatitis, compared to saline-treated controls. KGF preserved plasma citrulline and tumor necrosis factor-a levels, both indicative for reduced injury to the gastrointestinal tract. This was confirmed by histological findings. At 6 months after transplantation, survival rates were significantly higher in KGF-treated animals as compared to phosphate buffered saline-treated controls. These results indicate that KGF preserves gut integrity and might therefore contribute substantially to reduction of lethal GVHD in (nonmyeloablative) haploidentical transplantation. Bone Marrow Transplantation (2005) 36, 907-915.

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Section: Kgf Decreases Injury To the Gastrointestinal Tractmentioning

confidence: 99%

Keratinocyte growth factor ameliorates acute graft-versus-host disease in a novel nonmyeloablative haploidentical transplantation model

Vanclée

Lutgens

Oving

et al. 2005

Bone Marrow Transplant

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“…It is an excitatory neurotransmitter in the central nervous system of mammals (Watkins and Evans 1981) and functions as both substrate and product in many distinct reactions. It serves as a precursor molecule for the synthesis of various metabolites including N-acetyl-L-glutamate, δ-1-Pyrroline-5-carboxylate, β-citrylglutamate, L-γ-glutamyl-L-cysteine (Sonoda and Tatibana 1983;Wakabayashi et al 1991b;Collard et al 2010;Tu and Anders 1998;Battaglioli et al 2003). Glutamate is synthesized from glutamine, α-ketoglutarate and 5-oxoproline (Hu et al 2010;Cho et al 2001;Chen et al 1998).…”

Section: Introductionmentioning

confidence: 99%

A pathway map of glutamate metabolism

Yelamanchi

Jayaram

Thomas

et al. 2015

J. Cell Commun. Signal.

113

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Glutamate metabolism plays a vital role in biosynthesis of nucleic acids and proteins. It is also associated with a number of different stress responses. Deficiency of enzymes involved in glutamate metabolism is associated with various disorders including gyrate atrophy, hyperammonemia, hemolytic anemia, γ-hydoxybutyric aciduria and 5-oxoprolinuria. Here, we present a pathway map of glutamate metabolism representing metabolic intermediates in the pathway, 107 regulator molecules, 9 interactors and 3 types of post-translational modifications. This pathway map provides detailed information about enzyme regulation, protein-enzyme interactions, post-translational modifications of enzymes and disorders due to enzyme deficiency. The information included in the map was based on published experimental evidence reported from mammalian systems.

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“…Experimental and clinical data suggest a non-homogenous distribution of citrulline production. The distribution of P5CS activity in rats was 26%, 31%, 33% and 10% in the duodenum, upper jejunum, lower jejunum and ileum, respectively [120] . The release of citrulline measured as venous minus arterial concentration in patients admitted for elective gastrointestinal surgery was 30.4 ± 4.0 μmol/L and 8.4 ± 1.7 μmol/L for the jejunum and ileum, respectively [111] .…”

Section: Source Of Circulating Citrullinementioning

confidence: 88%

“…P5CS is unique to small intestinal enterocytes [116,[119][120][121] . PDG converts glutamine to glutamate and ammonia.…”

Section: Pathways For Citrulline Synthesismentioning

confidence: 99%

“…Thus high activities of OCT [153] , CPSI [153] and PROox [121,123] are found in the small intestine and liver. P5CS activity is almost exclusively found in small intestinal enterocytes [116,120,121] . This unique enzymatic profile, the unique role of the small intestine in whole body glutamine metabolism [96,154] and the relatively high small bowel enterocyte cell mass [126] make the small bowel epithelium the most important source of circulating citrulline [128,131] .…”

Section: Determinants Of Intestinal Citrulline Synthesis and Plasma Cmentioning

confidence: 99%

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Biomarkers for radiation-induced small bowel epithelial damage: An emerging role for plasma Citrulline

Lutgens¹,

Lambin²

2007

WJG

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Reduction of cancer treatment-induced mucosal injury has been recognized as an important target for improving the therapeutic ratio as well as reducing the economic burden associated with these treatment related sequellae. Clinical studies addressing this issue are hampered by the fact that specific objective parameters, which enable monitoring of damage in routine clinical practice, are lacking. This review summarizes pros and cons of currently available endpoints for intestinal injury. The metabolic background and characteristics of plasma citrulline, a recently investigated biomarker specifically for small intestinal injury, are discussed in more detail.

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Enzymological evidence for the indispensability of small intestine in the synthesis of arginine from glutamate

Cited by 43 publications

References 21 publications

Keratinocyte growth factor ameliorates acute graft-versus-host disease in a novel nonmyeloablative haploidentical transplantation model

Keratinocyte growth factor ameliorates acute graft-versus-host disease in a novel nonmyeloablative haploidentical transplantation model

A pathway map of glutamate metabolism

Biomarkers for radiation-induced small bowel epithelial damage: An emerging role for plasma Citrulline

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