Amino acid transport in mammalian kidney: Multiple systems for imino acids and glycine in rat kidney

Mohyuddin, Fazl; Cr, Scriver

doi:10.1152/ajplegacy.1970.219.1.1

Cited by 64 publications

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“…All previous studies of renal proline transport other than those with membrane vesicles (12) have reported extensive metabolism (4,11,13,14). This metabolism does not interfere with an assessment of the parameters of uptake such as the apparent Km.…”

Section: Discussionmentioning

confidence: 91%

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L-Proline Transport by Isolated Renal Tubules from Newborn and Adult Rats

et al. 1983

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SummaryProline uptake and metabolism has been examined in newborn Sprague-Dawley rat kidney and compared to that in adult animals.[14CJ-Proline uptake by renal tubule fragments from newborn rats occurs at the same initial rate as in adult tubules, but at physiologic concentrations achieves significantly higher intracellular levels after 15 min of incubation. Considerable metabolism of the proline taken up was observed in tissue of both ages. Analysis of acid soluble and insoluble tubule fractions from newborn and adults indicates similar degrees of proline incorporation into protein and oxidation to CO2 relative to the amount of radioactivity taken up. A major difference exists, however, with respect to the labeled components of the acid extract: adult tubules convert [ l4 CJ-proline to metabolites at a rate twice that of newborn. Analysis of concentration-dependent uptake data reveals two distinct entry systems for proline in both isolated newborn and adult tubules. No difference in the Km or Vmax was found between the young and mature tubules. SpeculationThese data indicate that the higher proline excretion by newborn animals is not the consequence of impaired uptake or the absence of any component of the process mediating proline influx, but must be related to other factors involved in the transcellular movement of the amino acid from the tubule lumen to the peritubular capillary.The physiologic hyperaminoaciduria observed in the young of several species (6, 25) has stimulated a number of investigations to determine the underlying developmental alterations in renal tubule transport mechanisms. The impetus for such studies has been not only to increase understanding of normal transport processes but also to gain insight into aberrant transport as observed in inherited disorders such as iminoglycinuria. Indeed, many in vitro experiments have focused on the differences in uptake of glycine and proline by various tubule cell preparations of newborn and adult rats. As a result of early studies with renal cortical slices two divergent points of view emerged. Scriver's group (3, 4, 5) had shown slow uptake in very young tissue and the absence of a high affmity transport system for both glycine and proline which appeared during tubule development. On the other hand, in our own laboratory, employing both cortical slices and renal tubule fragments, we consistently observed the presence of two distinct transport systems for glycine in the newborn as in the adult and stressed other possible reasons for the aminoaciduria than diminished glycine uptake (15,18,24).Although these fundamental discrepancies have been attributed to methodologic or rat strain differences, an extensive analysis of these factors has shown the presence of two distinct glycine transport systems in the newborn rat. In resolving the debate over development of glycine transport in rat kidney, we espoused the advantages of using separated tubule fragments rather than cortical slices to assess transport kinetics. The tubule fragment preparation eliminate...

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Section: Discussionmentioning

confidence: 91%

“…This metabolism does not interfere with an assessment of the parameters of uptake such as the apparent Km. Although the Vmax values may alter when incorporation into protein or oxidation is considered in calculation of amounts taken up, the Km does not change (4,14).…”

Section: Discussionmentioning

confidence: 99%

L-Proline Transport by Isolated Renal Tubules from Newborn and Adult Rats

et al. 1983

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“…Among the known transport systems are ( I ) two types of genetically controlled mechanism (10, 12): the first of these, a common system, has low specificity and high capacity; the other has lower capacity and high substrate specificity for either iminoacids or glycine; (2) other more dissociated mechanisms apparently existing in the kidney (5,8).…”

Section: Discussionmentioning

confidence: 99%

Type I Hyperprolinemia: A Study of the Intestinal Absorption of Proline, Hydroxyproline, and Glycine

Farriaux¹,

Dhondt²

1976

Pediatr Res

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“…The presence of a significant residual transport activity with unusual characteristics in mutant homozygotes, unmasked by the deletion of the proposed shared system, was the fust indication for heterogeneity of transport mechanisms for imino acids and glycine in human kidney (16,18,24). Subsequent studies with thin cortex slices prepared from rat (13) and human kidney (9) revealed the presence of more than one transport mediation for renal uptake of imino acids and glycine. Similar findings were obtained from isolated rabbit renal tubule segments (7,8).…”

Section: Hyperiminoglymentioning

confidence: 99%

Ontogeny of Amino Acid Reabsorption in Human Kidney. Evidence from the Homozygous Infant with Familial Renal Iminoglycinuria for Multiple Proline and Glycine Systems

Lasley

Scriver

1979

Pediatr Res

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Summaryadditional transport process(es) in the renal tubule, perhaps one with a preference for iminoacids and another with preference for seven infants French Canadim9' Our J e~s h , glycine (16,24). Since net reabsorption is determined to a great and one Greek) with massive selective hyperiminoglycinuria (proline, hydroxyproline, and glycine) were detected by urine screening extent by brush border membrane transport activity of the proxiin the second week of life. Follow-up investigations and family ma1 tubule (19,20), in this instance a benign mutation appears to studies revealed that each subject had a benign condition, frmilial be a useful probe, revealing the presence of more than one renal iminoglycinuria, an autosomal recessive condition. transport system serving iminoacids and glycine in that membrane of tubular epithelial cells. In this report, we have used the occurThe family studies ( Table 1 and Fig. 1) indicate the presence of rence of ontogeny and mutation together to examine this possiat least two different mutant alleles segregating in this small group bility in the human infant. of probands. Homozygotes of two forms and one genetic compound were identified.Quantitative studies revealed normal concentrations of proline (Table 2). Frat-azi Jewish, and one Greek), each with exceptional iminoglycinuria, tional excretion (c&ccR) of both proline and glyche in the were discovered in the second week of life by the urine screening probands was far in excess of that expected for the noranal program of the Quebec Network of Genetic ~e d i c i n e (10, 25). postnatal infant; F E~ and F E~~~ 100% of the filtered After follow-up qualitative studies had confirmed the presence load on occasion (~i~. 4). A of maturing reab-of persistent massive iminoglycinuria, each infant was admitted, sorptive activity was apparent in the proband group. probe with informed consent, as a day patient to the Clinical Investigareabsorption earlier than glycine reabsorption in the tion Unit at the Montreal Children's Hospital. More than one homozygotes (and the genetic compound) as it does in the normal quantitative study was performed during the first year of life in infants (Fig. 5).five of the patients (the probands for pedigrees 1, 2, 3, 4, and 6) Our fmdmgs suggest that three gene products serve net tubular and repeat qualitative studies were possible in six (the aforemenreabsorption of imino acids and glycine in human kidney. one, tioned probands plus proband 5). Family studies confirmed the affected by mutation in our patients, is responsible for a shared hereditary nature of the condition in all seven probands. *ansport activity; a second with preference for proline, and not For quantitative studies, a timed morning urine wllection was by the mutation, has an schedule of postnatal obtained in the fasting state. Glucose-water (5% w/v) was offered maturation; and a third with preference for glyche, also not to increase the urine rate during the by the mutation, has a schedule of maturation. period which lasted about 3 hr. Ur...

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Amino acid transport in mammalian kidney: Multiple systems for imino acids and glycine in rat kidney

Cited by 64 publications

References 0 publications

L-Proline Transport by Isolated Renal Tubules from Newborn and Adult Rats

L-Proline Transport by Isolated Renal Tubules from Newborn and Adult Rats

Type I Hyperprolinemia: A Study of the Intestinal Absorption of Proline, Hydroxyproline, and Glycine

Ontogeny of Amino Acid Reabsorption in Human Kidney. Evidence from the Homozygous Infant with Familial Renal Iminoglycinuria for Multiple Proline and Glycine Systems

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