Renal Aminoacidurias
A group of inherited kidney disorders characterized by the abnormally elevated levels of AMINO ACIDS in URINE. Genetic mutations of transport proteins result in the defective reabsorption of free amino acids at the PROXIMAL RENAL TUBULES. Renal aminoaciduria are classified by the specific amino acid or acids involved.
Arginine transport through system y(+)L in cultured human fibroblasts: normal phenotype of cells from LPI subjects. (1/18)
In lysinuric protein intolerance (LPI), impaired transport of cationic amino acids in kidney and intestine is due to mutations of the SLC7A7 gene. To assess the functional consequences of the LPI defect in nonepithelial cells, we have characterized cationic amino acid (CAA) transport in human fibroblasts obtained from LPI patients and a normal subject. In both cell types the bidirectional fluxes of arginine are due to the additive contributions of two Na(+)-independent, transstimulated transport systems. One of these mechanisms, inhibited by N-ethylmaleimide (NEM) and sensitive to the membrane potential, is identifiable with system y(+). The NEM- and potential-insensitive component, suppressed by L-leucine only in the presence of Na(+), is mostly due to the activity of system y(+)L. The inward and outward activities of the two systems are comparable in control and LPI fibroblasts. Both cell types express SLC7A1 (CAT1) and SLC7A2 (CAT2B and CAT2A) as well as SLC7A6 (y+LAT2) and SLC7A7 (y+LAT1). We conclude that LPI fibroblasts exhibit normal CAA transport through system y(+)L, probably referable to the activity of SLC7A6/y+LAT2. (+info)Heteromeric amino acid transporters: biochemistry, genetics, and physiology. (2/18)
The heteromeric amino acid transporters (HATs) are composed of two polypeptides: a heavy subunit (HSHAT) and a light subunit (LSHAT) linked by a disulfide bridge. HSHATs are N-glycosylated type II membrane glycoproteins, whereas LSHATs are nonglycosylated polytopic membrane proteins. The HSHATs have been known since 1992, and the LSHATs have been described in the last three years. HATs represent several of the classic mammalian amino acid transport systems (e.g., L isoforms, y(+)L isoforms, asc, x(c)(-), and b(0,+)). Members of the HAT family are the molecular bases of inherited primary aminoacidurias cystinuria and lysinuric protein intolerance. In addition to the role in amino acid transport, one HSHAT [the heavy subunit of the cell-surface antigen 4F2 (also named CD98)] is involved in other cell functions that might be related to integrin activation. This review covers the biochemistry, human genetics, and cell physiology of HATs, including the multifunctional character of CD98. (+info)ESTIMATION OF ALPHA-AMINO NITROGEN IN PLASMA AND URINE BY THE COLORIMETRIC NINHYDRIN REACTION. (3/18)
Methods are described for the estimation of plasma and urine alpha-amino nitrogen by the colorimetric ninhydrin reaction; in the method for urine, both ammonia and urea are separated by a rapid ion-exchange resin procedure. Two methods of estimation are given; one has the advantage of great simplicity, but involves the use of cyanide; in the other, cyanide is eliminated. Normal values are reported; they correspond well with those obtained by the gasometric ninhydrin method. (+info)PATHOLOGICAL FINDINGS IN HOMOCYSTINURIA. (4/18)
Pathological findings are described in four cases of a new aminoaciduria in which homocystine is excreted in the urine. All the patients were mentally retarded children. Three of them presented diagnostic features of Marfan's syndrome. Necropsy on one case and biopsy findings in the others are described. Fatty change occurs in the liver. The most striking lesions are vascular. Metachromatic medial degeneration of the aorta and of the elastic arteries in the necropsied case are considered in relation to Marfan's syndrome. Other changes, particularly thrombosis which is prevalent in homocystinuria, suggest the possibility of a platelet defect. The findings are discussed in respect of an upset in the metabolism of sulphur-containing amino-acids and with particular reference to Marfan's syndrome. (+info)SOME AIDS IN THE DIAGNOSIS OF GENETIC DISORDERS. (5/18)
Disorders of genetic origin may cause morphological or metabolic disturbances. A number of recognized screening procedures, e.g. palm printing, buccal smears and paper chromatography, are useful in the recognition of these disorders.Additional procedures for more detailed analysis of the genetic defects, e.g. aminoacid analysis, gas chromatography and chromosome analysis, have been developed and are employed in specialized centres. (+info)The genetics of heteromeric amino acid transporters. (6/18)
Heteromeric amino acid transporters (HATs) are composed of a heavy (SLC3 family) and a light (SLC7 family) subunit. Mutations in system b(0,+) (rBAT-b(0,+)AT) and in system y(+)L (4F2hc-y(+)LAT1) cause the primary inherited aminoacidurias (PIAs) cystinuria and lysinuric protein intolerance, respectively. Recent developments [including the identification of the first Hartnup disorder gene (B0AT1; SLC6A19)] and knockout mouse models have begun to reveal the basis of renal and intestinal reabsorption of amino acids in mammals. (+info)Aminoaciduria and altered renal expression of luminal amino acid transporters in mice lacking novel gene collectrin. (7/18)
Defects in renal proximal tubule transport manifest in a number of human diseases. Although variable in clinical presentation, disorders such as Hartnup disease, Dent's disease, and Fanconi syndrome are characterized by wasting of solutes commonly recovered by the proximal tubule. One common feature of these disorders is aminoaciduria. There are distinct classes of amino acid transporters located in the apical and basal membranes of the proximal tubules that reabsorb >95% of filtered amino acids, yet few details are known about their regulation. We present our physiological characterization of a mouse line with targeted deletion of the gene collectrin that is highly expressed in the kidney. Collectrin-deficient mice display a reduced urinary concentrating capacity due to enhanced solute clearance resulting from profound aminoaciduria. The aminoaciduria is generalized, characterized by loss of nearly every amino acid, and results in marked crystalluria. Furthermore, in the kidney, collectrin-deficient mice have decreased plasma membrane populations of amino acid transporter subtypes B(0)AT1, rBAT, and b(0,+)AT, as well as altered cellular distribution of EAAC1. Our data suggest that collectrin is a novel mediator of renal amino acid transport and may provide further insight into the pathogenesis of a number of human disease correlates. (+info)Loss-of-function mutations in the glutamate transporter SLC1A1 cause human dicarboxylic aminoaciduria. (8/18)
(+info)Renal Aminoacidurias are inherited tubular disorders characterized by the abnormal excretion of amino acids in the urine due to defects in the renal tubular reabsorption process.
Renal aminoacidurias are a group of inherited kidney disorders characterized by the abnormal excretion of amino acids in the urine (aminoaciduria). This condition results from defects in the renal tubular transport systems that are responsible for the reabsorption of amino acids from the filtrate in the kidneys.
There are several types of renal aminoacidurias, each associated with a specific genetic mutation affecting different transporter proteins in the proximal renal tubules. The most common type is cystinuria, which is caused by a defect in the transport system for four amino acids: cystine, ornithine, lysine, and arginine. Other types of renal aminoacidurias include Hartnup disorder, Lowe syndrome, and Dent disease, among others.
The clinical manifestations of renal aminoacidurias vary depending on the specific type and severity of the disorder. Some individuals may be asymptomatic or have only mild symptoms, while others may experience severe complications such as kidney stones, urinary tract infections, neurological symptoms, or growth retardation.
Treatment for renal aminoacidurias typically involves dietary modifications, increased fluid intake, and medications to reduce the risk of kidney stone formation and other complications. In some cases, surgery may be necessary to remove large kidney stones.