Dicarboxylic aminoaciduria: An inborn error of glutamate and aspartate transport with metabolic implications, in combination with a hyperprolinemia

Teijema, H L; Gelderen, H. H. van; Giesberts, M. A. H.; Angulo, Mario

doi:10.1016/0026-0495(74)90108-5

Cited by 63 publications

(22 citation statements)

References 10 publications

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Section: Introductionmentioning

confidence: 99%

“…DA is an autosomal recessive disorder with an estimated frequency of 1:36,000 (1), which was first described in 1974 (2). The clinical features of the disorder have not been widely explored, due to the paucity of clinical cases; however, of the 4 independent cases examined, 2 report an association with mental retardation (2,3). Solute carrier family 1, member 1 (SLC1A1), also referred to in human studies as excitatory amino acid transporter 3 (EAAT3) or in rodents as excitatory amino acid carrier 1 (EAAC1), is a high-affinity anionic amino acid transporter expressed in the kidney, a wide variety of epithelial tissues, brain, and eye.…”

Section: Introductionmentioning

confidence: 99%

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Loss-of-function mutations in the glutamate transporter SLC1A1 cause human dicarboxylic aminoaciduria

Bailey¹,

Ryan²,

Thoeng³

et al. 2011

J. Clin. Invest.

130

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Solute carrier family 1, member 1 (SLC1A1; also known as EAAT3 and EAAC1) is the major epithelial transporter of glutamate and aspartate in the kidneys and intestines of rodents. Within the brain, SLC1A1 serves as the predominant neuronal glutamate transporter and buffers the synaptic release of the excitatory neurotransmitter glutamate within the interneuronal synaptic cleft. Recent studies have also revealed that polymorphisms in SLC1A1 are associated with obsessive-compulsive disorder (OCD) in early-onset patient cohorts. Here we report that SLC1A1 mutations leading to substitution of arginine to tryptophan at position 445 (R445W) and deletion of isoleucine at position 395 (I395del) cause human dicarboxylic aminoaciduria, an autosomal recessive disorder of urinary glutamate and aspartate transport that can be associated with mental retardation. These mutations of conserved residues impeded or abrogated glutamate and cysteine transport by SLC1A1 and led to near-absent surface expression in a canine kidney cell line. These findings provide evidence that SLC1A1 is the major renal transporter of glutamate and aspartate in humans and implicate SLC1A1 in the pathogenesis of some neurological disorders.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Loss-of-function mutations in the glutamate transporter SLC1A1 cause human dicarboxylic aminoaciduria

Bailey¹,

Ryan²,

Thoeng³

et al. 2011

J. Clin. Invest.

130

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“…The presence in the kidney of a specific acidic amino acid transport system is indicated from physiological studies of renal clearance and uptakes of different classes of amino acids in cortical slices and isolated renal cells [11,33,34,38,41]. Strong genetic support for this suggestion has come from reports of two cases of human dicarboxylic aminoaciduria [18,36]. Studies of transtubular rates of flux in microperfused tubules have demonstrated that dicarboxylic amino acid transport is Na + dependent [37].…”

mentioning

confidence: 95%

Sodium gradient- and sodium plus potassium gradient-dependentl-glutamate uptake in renal basolateral membrane vesicles

et al. 1981

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A membrane preparation enriched in the basolateral segment of the plasma membrane was isolated from the rat renal cortex by a procedure that included separation of particulates on a self-generating Percoll gradient. The uptake of L-glutamate by the basolateral membrane vesicles was studied. A Na+ gradient (Na+]o greater than [Na+]i) stimulated the uptake of L-glutamate and provided the driving force for the uphill transport of the acidic amino acid, suggesting a Na+-L-glutamate cotransport system in the basolateral membrane. A K+ gradient ([K+]i greater than [K+]o) increased the uptake additionally. This effect was specific for K+(Rb+). The action of the K+ gradient in enhancing the uptake of L-glutamate had an absolute requirement for Na+. In the presence of Na+, but in the absence of a Na+ gradient. i.e., [Na+]o = [Na+]i, the K+ gradient also energized the concentrative uptake of L-glutamate. This effect of the K+ gradient was not attributable to an alteration in membrane potential. The finding of a concentrative uptake system for L-glutamate energized by both Na+ ([Na+]o greater than [Na+]i and K+ ([K+]o) gradients in the basolateral membrane, combined with previous reports of an ion gradient-dependent uphill transport system for this amino acid in the brush border membrane, suggests a mechanism by which L-glutamate is accumulated intracellularly in the renal proximal tubule to extraordinarily high concentrations.

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“…The venous heparin blood was ice-chilled immediately, kept at 2~ and at native pH during deproteinization by centriflo ultrafiltration, and the ultrafiltrates were stored at -75~ All amino acids are well preserved by this technique [19], and were well separated by lithium buffer elution appiied to an aminoacid analyzer, fl-Hydroxybutyrate and acetoacetate were assayed enzymatically [22]. Whole blood glucose was estimated by a glucose oxidase method [20] which permitted a reproducibility of i%.…”

Section: Methodsmentioning

confidence: 99%

Hypoketosis as a cause of symptoms in childhood hypoglycemia

1980

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Children with symptomatic hypoglycemia and asymptomatic hypoglycemia-prone children were shown to differ in the degree of ketosis after a 20 h fast. In the latter children the close negative correlation between ketone body levels and glucose levels yielded a regression line against which the former children's data could be compared. Half of the patients were found to be hypoketotic during hypoglycemia. The significance of this hypoketosis in the symptomatology is discussed. The finding of other abnormal responses to fasting, particularly in the patients' nitrogen metabolism, suggests that all these aberrations have a common cause which may be of hepatic origin.

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Dicarboxylic aminoaciduria: An inborn error of glutamate and aspartate transport with metabolic implications, in combination with a hyperprolinemia

Cited by 63 publications

References 10 publications

Loss-of-function mutations in the glutamate transporter SLC1A1 cause human dicarboxylic aminoaciduria

Loss-of-function mutations in the glutamate transporter SLC1A1 cause human dicarboxylic aminoaciduria

Sodium gradient- and sodium plus potassium gradient-dependentl-glutamate uptake in renal basolateral membrane vesicles

Hypoketosis as a cause of symptoms in childhood hypoglycemia

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