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Defining the role of 4-hydroxy-2-oxoglutarate aldolase in hydroxyproline metabolism and primary hyperoxaluria

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abstract
Aberrant glyoxylate metabolism is a hallmark of primary hyperoxaluria (PH). PH types 1 and 2 are the consequence of functional defects in alanine-glyoxylate aminotransferase (AGT) and glyoxylate reductase (GR), respectively. The resulting increase in oxalate excretion can lead to the formation of calcium oxalate kidney stones, renal calcium oxalate deposition, and in extreme cases renal failure. Recent evidence has shown that the degradation of 4-hydroxyproline (Hyp), generated from endogenous and dietary sources, leads to an increase in glycolate and oxalate levels in plasma and urine. Furthermore, it has been shown that Hyp metabolism is likely the major contributor to the glyoxylate pool which can then go on to form oxalate in PH patients. Therefore, inhibition of Hyp degradation represents a novel therapeutic opportunity for diminishing endogenous oxalate production in patients with PH.
subject
glyoxylate
hydroxyproline
primary hyperoxaluria
contributor
Riedel, Travis Joel (author)
Lowther, William T (committee chair)
Hantgan, Roy R (committee member)
Hollis, Thomas (committee member)
Lyles, Douglas S (committee member)
date
2012-06-12T08:35:38Z (accessioned)
2013-06-12T08:30:11Z (available)
2012 (issued)
degree
Biochemistry and Molecular Biology (discipline)
embargo
2013-06-12 (terms)
identifier
http://hdl.handle.net/10339/37245 (uri)
language
en (iso)
publisher
Wake Forest University
title
Defining the role of 4-hydroxy-2-oxoglutarate aldolase in hydroxyproline metabolism and primary hyperoxaluria
type
Dissertation

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