Amino Acid Transport

Ellory, J. C.; Swietach, Pawel; Gibson, John S.

doi:10.1007/978-3-662-05181-8_12

Cited by 4 publications

(2 citation statements)

References 58 publications

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“…The demonstration that d-amphetamine is generated from LDX in red blood cell cytosol raises the question of the nature of the transport of LDX across the red blood cell plasma membrane. While investigating LDX transport was not an objective of the present work, the dipeptide-like properties of the drug, combined with the capacity of red blood cells to take up cationic dipeptides 14 and the presence of high-affinity amino acid transporters in the red blood cell plasma membrane, 15 are suggestive of a mechanism for future investigation. Furthermore, it is noteworthy that LDX is actively taken up from the gastrointestinal tract via peptide transporter-1.…”

Section: Discussionmentioning

confidence: 99%

Lisdexamfetamine prodrug activation by peptidase-mediated hydrolysis in the cytosol of red blood cells

Murkett¹,

Sharman²,

Pennick³

2014

NDT

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Lisdexamfetamine dimesylate (LDX) is approved as a once-daily treatment for attention-deficit/hyperactivity disorder in children, adolescents, and adults in some countries. LDX is a prodrug comprising d-amphetamine covalently linked to l-lysine via a peptide bond. Following oral administration, LDX is rapidly taken up from the small intestine by active carrier-mediated transport, probably via peptide transporter 1. Enzymatic hydrolysis of the peptide bond to release d-amphetamine has previously been shown to occur in human red blood cells but not in several other tissues. Here, we report that LDX hydrolytic activity resides in human red blood cell lysate and cytosolic extract but not in the membrane fraction. Among several inhibitors tested, a protease inhibitor cocktail, bestatin, and ethylenediaminetetra-acetic acid each potently inhibited d-amphetamine production from LDX in cytosolic extract. These results suggest that an aminopeptidase is responsible for hydrolytic cleavage of the LDX peptide bond, although purified recombinant aminopeptidase B was not able to release d-amphetamine from LDX in vitro. The demonstration that aminopeptidase-like activity in red blood cell cytosol is responsible for the hydrolysis of LDX extends our understanding of the smooth and consistent systemic delivery of d-amphetamine by LDX and the long daily duration of efficacy of the drug in relieving the symptoms of attention-deficit/hyperactivity disorder.

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Section: Discussionmentioning

confidence: 99%

Lisdexamfetamine prodrug activation by peptidase-mediated hydrolysis in the cytosol of red blood cells

Murkett¹,

Sharman²,

Pennick³

2014

NDT

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“…It is reported that methionine, lysine, threonine, arginine, isoleucine and valine with the last three being limited essentially equally[17] based on maize and soy fed chickens. However, because the L system usually has a high transport capacity, presumably due to a high level of expression, even a poor substrate may achieve a significant flux via system[40]. The same at 34 weeks of age expression of only one L system aat increased upon Se supplementation, hence might have not contributed to deficiency of amino acids.…”

mentioning

confidence: 99%

Differential Level of Hormones Amino Acids Expression of Amino Acid Transporters and Hormone Receptors during Early and Mid Laying Period and their Modulation by Organic Selenium in Vanaraja Chickens

Nidamanuri,

Ravindra Konadeka,

Sivalingam

et al. 2023

Act Sci VetSci

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The present study was conducted to compare the plasma levels of melatonin, ghrelin, steroid hormones, amino acids, expression of hormone receptors (MNTR, GHLR), and amino acid transporters (AAts, 4 nos.) during early (EP, 24-28 weeks) and mid (MP, 32-36 weeks) laying period. Hormones melatonin and ghrelin have been associated with ovarian function in chickens. Till date no reports are available with respect to mentioned physiological parameters on the production performance and their modulation by Se (selenium) treatment in Vanaraja Chickens. Vanaraja chickens at 22 weeks of age were divided equally into two groups. Control group was reared on a basal diet containing 0.3mg of inorganic Se. Treatment group was offered additional 0.3mg of organic Se enriched yeast during EP and MP. When compared between the control groups of EP and MP, the mean level of all the hormones was higher at EP.The expression of all the AAts and MNTR was higher in jejunum, compared to magnum, except for CAT and GHLR during EP. When compared to control group supplementation of selenium increased the level of plasma hormones and amino acids significantly (P < 0.05) during MP. When compared between EP and MP, treatment with Se increased expression of 2-3 number of aats and decreased MNTR in both the tissues significantly at EP, whereas expression of only GHLR increased in magnum. The Se treatment did not cause significant change in the expression of receptors, at MP. In conclusion, additional Se supplementation increased the utilization of hormones and modulation of the physiological parameters was higher in magnum tissue resulting in a beneficial effect on increased egg production (2%), and body weight (P < 0.01) during EP and MP.

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Effect of Copper on l-Cysteine/l-Cystine Influx in Normal Human Erythrocytes and Erythrocytes of Wilson’s Disease

et al. 2016

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Wilson's disease is a disease of abnormal copper metabolism in which free serum copper level is raised. The objective of the study was to determine, whether in Wilson disease, L-cysteine/L-cystine influx into RBC was decreased or not and the specific amino acid transporter affected by copper in normal human RBC. For L-cysteine/L-cystine influx, ten untreated cases, ten treated cases and ten age and sex matched healthy controls were recruited. To study the effect of copper on L-cysteine/Lcystine influx in RBC, 15 healthy subjects were selected. RBC GSH and L-cysteine/L-cystine influx were estimated by Beautler's and Yildiz's method respectively. In untreated cases, L-cysteine/L-cystine influx and erythrocyte GSH level were decreased showing that elevated level of free copper in serum or media decreased L-cysteine/Lcystine influx in human RBC. Copper treatment inhibited L amino acid transporter in normal RBC specifically.

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Amino Acid Transport

Cited by 4 publications

References 58 publications

Lisdexamfetamine prodrug activation by peptidase-mediated hydrolysis in the cytosol of red blood cells

Lisdexamfetamine prodrug activation by peptidase-mediated hydrolysis in the cytosol of red blood cells

Differential Level of Hormones Amino Acids Expression of Amino Acid Transporters and Hormone Receptors during Early and Mid Laying Period and their Modulation by Organic Selenium in Vanaraja Chickens

Effect of Copper on l-Cysteine/l-Cystine Influx in Normal Human Erythrocytes and Erythrocytes of Wilson’s Disease

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Amino Acid Transport

Cited by 4 publications

References 58 publications

Lisdexamfetamine prodrug activation by peptidase-mediated hydrolysis in the cytosol of&nbsp;red blood cells

Lisdexamfetamine prodrug activation by peptidase-mediated hydrolysis in the cytosol of&nbsp;red blood cells

Differential Level of Hormones Amino Acids Expression of Amino Acid Transporters and Hormone Receptors during Early and Mid Laying Period and their Modulation by Organic Selenium in Vanaraja Chickens

Effect of Copper on l-Cysteine/l-Cystine Influx in Normal Human Erythrocytes and Erythrocytes of Wilson’s Disease

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Lisdexamfetamine prodrug activation by peptidase-mediated hydrolysis in the cytosol of red blood cells

Lisdexamfetamine prodrug activation by peptidase-mediated hydrolysis in the cytosol of red blood cells