Membrane Transport of l-Arginine and Cationic Amino Acid Analogs

Closs, Ellen I.; Mann, Giovanni E.

doi:10.1016/b978-012370420-7/50015-0

Cited by 18 publications

(22 citation statements)

References 109 publications

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“…The bioavailability of arginine is further decreased by increased ornithine levels because ornithine and arginine compete for the same transporter system for cellular uptake. 26,27 Endogenous synthesis of arginine from citrulline may be compromised by renal dysfunction, commonly associated with SCD. Despite an increase in NOS, [10][11][12] NO bioavailability in SCD is low due to low substrate availability, [1][2][3]16 NO scavenging by cell free hemoglobin released during hemolysis, 5 and through reactions with free radicals such as superoxide.…”

Section: Collagen Production and Depositionmentioning

confidence: 99%

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Dysregulated Arginine Metabolism, Hemolysis-Associated Pulmonary Hypertension, and Mortality in Sickle Cell Disease

Morris¹

2005

JAMA

664

682

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L-ARGININE, THE SUBSTRATE FOR nitric oxide (NO) synthesis, is deficient in sickle cell disease (SCD). [1][2][3][4] Increased NO consumption by cell free plasma hemoglobin 5 and reactive oxygen species 6,7 leads to decreased NO bioavailability 8,9 that is exacerbated by decreased availability of the NO synthase substrate L-arginine. This state of resistance to NO is accompanied by a compensatory up-regulation of NO synthase and non-NO-dependent vasodilators. [10][11][12][13] Under conditions of low arginine concentration, NO synthase is uncoupled, producing reactive oxygen species in lieu of NO, 14,15 potentially further reducing NO bioavailability in SCD and enhancing oxidative stress. Recent reports of elevated arginase activity in SCD [16][17][18] offer another avenue for decreasedargininebioavailability.Arginase, an enzyme that converts L-arginine to ornithine and urea, can limit NO bioavailability through increased consumption of the substrate for NO synthase. [19][20][21] Arginase, which is found predominantly

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Section: Collagen Production and Depositionmentioning

confidence: 99%

“…20,24,25 Furthermore, since arginine and ornithine compete for the same transport system for cellular uptake, 26,27 a decrease in the ratio of arginine to ornithine resulting from increased arginase activity could further limit arginine bioavailability for NO synthesis.…”

mentioning

confidence: 98%

Dysregulated Arginine Metabolism, Hemolysis-Associated Pulmonary Hypertension, and Mortality in Sickle Cell Disease

Morris¹

2005

JAMA

664

682

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“…According to the model with 14 TMs, the region divergent between CAT-2A and -2B is located in the fourth intracellular loop and in part of the adjacent TM IX. Interestingly, in this region, the three isoforms exhibiting similar transport properties (CAT-1, -2B, and -3) also show the highest percentage of amino acid sequence identity (3). It is noteworthy that CAT-2A and -2B demonstrate such divergent transport properties, even though their amino acid sequences differ only in 20 residues (within the stretch of 42 amino acids).…”

mentioning

confidence: 97%

Two Amino Acid Residues Determine the Low Substrate Affinity of Human Cationic Amino Acid Transporter-2A

Habermeier

Wolf

Martiné

et al. 2003

Journal of Biological Chemistry

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Mammalian cationic amino acid transporters (CAT) differ in their substrate affinity and sensitivity to transstimulation. The apparent K m values for cationic amino acids and the sensitivity to trans-stimulation of CAT-1, -2B, and -3 are characteristic of system y ؉ . In contrast, CAT-2A exhibits a 10-fold lower substrate affinity and is largely independent of substrate at the trans-side of the membrane. CAT-2A and -2B demonstrate such divergent transport properties, even though their amino acid sequences differ only in a stretch of 42 amino acids. Here, we identify two amino acid residues within this 42-amino acid domain of the human CAT-2A protein that are responsible for the apparent low affinity of both the extracellular and intracellular substrate-binding sites. These residues are located in the fourth intracellular loop, suggesting that they are not part of the translocation pathway. Rather, they may be responsible for the low affinity conformation of the substrate-binding sites. The sensitivity to trans-stimulation is not determined by the same amino acid residues as the substrate affinity and must involve a more complex interaction between individual amino acid residues. In addition to the 42-amino acid domain, the adjacent transmembrane domain X seems to be involved in this function.

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“…l- [14]). The CAT substrates not only compete with l-arginine for transport, but also drive the efflux of intracellular l-arginine, due to trans-stimulation.…”

Section: Pharmacological and Pharmaceutical Aspects Of Cat Transportersmentioning

confidence: 99%

CATs and HATs: the SLC7 family of amino acid transporters

Verrey

Closs

Wagner

et al. 2004

Pfl�gers Archiv European Journal of Physiology

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623

561

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Membrane Transport of l-Arginine and Cationic Amino Acid Analogs

Cited by 18 publications

References 109 publications

Dysregulated Arginine Metabolism, Hemolysis-Associated Pulmonary Hypertension, and Mortality in Sickle Cell Disease

Dysregulated Arginine Metabolism, Hemolysis-Associated Pulmonary Hypertension, and Mortality in Sickle Cell Disease

Two Amino Acid Residues Determine the Low Substrate Affinity of Human Cationic Amino Acid Transporter-2A

CATs and HATs: the SLC7 family of amino acid transporters

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