Renal tubular transport of proline, hydroxyproline, and glycine

Scriver, Charles R.

doi:10.1172/jci105776

Cited by 64 publications

(4 citation statements)

References 32 publications

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“…1; thus, the effect of 20 mM proline on uptake in the low glycine concentration range reflects the inhibition of the glycine high Km system. Our glycine uptake data lend further credence to the existence of a high affinity but low capacity unshared glycine system and a low affinity with high capacity glycineproline shared system in human kidney (18).…”

Section: Methodssupporting

confidence: 72%

Proline and glycine uptake by renal brushborder membrane vesicles.

McNamara¹,

Ozegović²,

Pepe³

et al. 1976

Proc. Natl. Acad. Sci. U.S.A.

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Uptake of L-proline and glycine by rat renal brushborder membrane vesicles was seen to be osmotically sensitive, pH dependent, and occurred in the absence of proline and glycine metabolism. The uptake system for proline was Na+ gradient dependent, and exhibited a dual system for entry, Km, = 0.067 mM and Km2 = 5.26 mM. The uptake of glycine was also Na+ gradient dependent, and exhibited a two Km system, Km, -0.22 mM and Kin = 4.00 mM. Studies of proline and glycine interactions indicate a shared site which has a lower affinity and higher capacity for glycine than for proline. The high affinity glycine site and low affinity proline site do not appear to be shared.The occurrence of inherited iminoglycinuria in man as well as a hyperexcretion of proline and glycine in the normal human neonate prompted numerous studies to delineate the mechanism of renal tubular reabsorption of proline and glycine. These employed rat renal cortical slices or isolated rabbit renal tubules in vitro and resulted in the concept of multiple systems for tubule cell uptake of glycine and proline (1-3). Inherent, however, in the use of such model systems is the difficulty of interpretation of transport data because of involvement of the two types of membranes of the proximal tubule cell, and the rapid metabolism of the substrates by these cells. Amino acid uptake by the tubule cells of the cortical slice or isolated tubule may take place either from the luminal brushborder or the basal smooth membrane, thereby making it difficult to discern the contribution of these membranes independently. In addition, proline taken into such cells was observed to be largely converted to intracellular glutamate, a process which may be a regulatory factor in the transport of proline across the membrane (4).Recently, Kinne and his associates described the preparation of purified rat kidney brushborder membranes and reported the uptake of phenylalanine (5) Membrane vesicles, suspended in Na+-free THM buffer at pH 7.4, were used for the transport studies. The standard uptake experiment, which is under conditions of a Na+ gradient unless otherwise stated, consisted of 0.5 ml of freshly prepared membrane vesicles in THM buffer at 220, which was added at the starting time to a disposable 10 X 75 mm test tube containing 0.1 ,Ci of 14C-labeled amino acid, 0.1 1ACi of 3-O-[methyl-3H]methyl-D-glucose, 50,umol of NaCl, and unlabeled amino acid to bring the incubation mixture to the desired final concentration of amino acid. The mixture was stirred on a Vortex genie for 6 sec. Membrane vesicles in THM buffer were preincubated with 100 mM NaCl for 40 min in experiments where uptake in the absence of Na+ gradient was to be studied.At various times ranging from 15 sec to 20 min, the incubation mixture was transferred by pasteur pipette to a Millipore filter apparatus. Uptake was stopped by rapid filtration of the mixture through a Millipore filter (HAWP, 0.45 nm) and washed once with 5 ml of 154 mM NaCI in 1 mM Tris-N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic ...

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Section: Methodssupporting

confidence: 72%

Proline and glycine uptake by renal brushborder membrane vesicles.

McNamara¹,

Ozegović²,

Pepe³

et al. 1976

Proc. Natl. Acad. Sci. U.S.A.

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“…The reabsorptive function is dependent on the integrity of membrane transport systems which serve low (physiological) and high intraluminal concentrations of proline (5). Saturability of a high-capacity mechanism for proline reabsorption has also been identified, with some difficulty, by microperfusion methods in rat kidney (18).…”

Section: Discussionmentioning

confidence: 99%

“…The opportunity to examine L-proline transport in kidney of the homozygous PRO/Re mouse (3,4), a mutant with less than 1% of the normal renal proline oxidase activity, was of particular interest to us. Proline is avidly taken up from urine (5) and from plasma (6) by mammalian kidney, where it is then vigorously oxidized, with resultant glucogenesis under conditions of fasting (6). It follows that the PRO/Re mouse offers a unique opportunity to examine the inter-relationships between intracellular metabolism of proline and the cellular architecture of renal absorbing epithelium; and how they influence proline uptake from extracellular fluid in vivo and in vitro and the net reclamative flux of proline from urine to blood in vivo.…”

mentioning

confidence: 99%

Role of epithelial architecture and intracellular metabolism in proline uptake and transtubular reclamation in PRO/re mouse kidney.

Scriver¹,

McInnes²,

Mohyuddin³

1975

Proc. Natl. Acad. Sci. U.S.A.

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The homozygous PRO/Re mouse has less than 1% of the very high proline oxidase activity that characterizes normal kidney cortex. In PRO/Re mouse the endogenous proline concentration is eight times normal in plasma and four times normal in kidney cortex cells, but 50 times normal in urine. The integrity of the membrane transport systems for proline uptake at the antiluminal surface of absorbing epithelium is retained in PRO/Re kidney, as determined by the slice method. Clearance studies in vivo under steady-state conditions indicate that the integrity of the luminal uptake system shared by glycine and proline, and serving proline absorption, is also intact. The exaggerated renal clearance of proline in PRO/Re mice (50 times normal) is explained when its raised intracellular concentration, caused by impaired proline oxidation, is considered. Backflux into urine flowing down the nephron will occur under these conditions, thus impairing net reclamation of proline in PRO/Re kidney. The findings reveal that membrane transport and intracellular metabolism of a substrate are, indeed, independent functions, but that metabolism of a substance can influence its transcellular transport.Transport across the plasma membrane and intracellular metabolism of an amino acid should be considered as independent functions (1). Awareness of this essential dichotomy has been heightened by the use of blocked-catabolic mutant microorganisms and metabolically inert substrates to study membrane transport of various amino acids (1, 2). The opportunity to examine L-proline transport in kidney of the homozygous PRO/Re mouse (3, 4), a mutant with less than 1% of the normal renal proline oxidase activity, was of particular interest to us. Proline is avidly taken up from urine (5) and from plasma (6) by mammalian kidney, where it is then vigorously oxidized, with resultant glucogenesis under conditions of fasting (6). It follows that the PRO/Re mouse offers a unique opportunity to examine the inter-relationships between intracellular metabolism of proline and the cellular architecture of renal absorbing epithelium; and how they influence proline uptake from extracellular fluid in vivo and in vitro and the net reclamative flux of proline from urine to blood in vivo.We used renal clearance methods (7) to evaluate tubular reclamation of proline across the luminal membrane, and the kidney cortex slice technique to measure transport across the antiluminal surfaces of epithelial cells (8). Normal mouse kidney transports L-proline in vitro by saturable energydependent membrane mechanisms, and can reclaim virtually all of the filtered proline from urine. This organ also oxidizes proline at exceptionally high rates. When proline oxidation is blocked, the intracellular proline pool is expanded in PRO/Re 1431 mouse kidney. Whereas, proline transport as a membrane function remains intact, net reclamation from urine is impaired in PROIRe mice, presumably because of proline backflux at the luminal side of the epithelium. METHODS AND MATERIALSHomozygous...

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“…Since passive diffusion contributes little to the uptake of amino acids into brain tissue (ABADOM & SCHOLE- FIELD, 1962;LAHIRI & LAJTHA, 1964), these findings would indicate that both separate and shared transport processes exist for the uptake of histidine from the circulation into the brain. The existence of both separate and shared transport mechanisms for the transport of amino acids into brain has not been reported, but evidence has accumulated (%RIVER & GOLDMAN, 1966;SCRIVER, 1968;MOHYUDDIN & SCRIVER, 1970) for the existence of three genetically distinct mechanisms for the renal transport of the imino acids and glycine, only one of which is shared by all three amino acids.…”

Section: Discussionmentioning

confidence: 99%

The Effect of High Concentrations of Histidine on the Level of Other Amino Acids in Plasma and Brain of the Mature Rat

Tyfield

Holton

1976

Journal of Neurochemistry

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—Changes in plasma and brain amino acids have been observed in adult rats 1 h after intraperitoneal injections of histidine and in others maintained on high histidine diets for 8 days. In the injection studies the compounds most consistently affected were the aromatic and branched chain amino acids and methionine. Reductions in their concentrations in the brain were explained by a competition with histidine for uptake into the tissue. There was little change in plasma amino acid levels. In the animals fed the highest concentration of histidine there was a generalized increase in brain, and a reduction in plasma, amino acid concentrations. A decrease in protein synthesis is postulated to explain this effect in brain.

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Renal tubular transport of proline, hydroxyproline, and glycine

Cited by 64 publications

References 32 publications

Proline and glycine uptake by renal brushborder membrane vesicles.

Proline and glycine uptake by renal brushborder membrane vesicles.

Role of epithelial architecture and intracellular metabolism in proline uptake and transtubular reclamation in PRO/re mouse kidney.

The Effect of High Concentrations of Histidine on the Level of Other Amino Acids in Plasma and Brain of the Mature Rat

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