R P Holmes1, D G Assimos. 1. Department of Urology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Abstract
PURPOSE: We define the major pathways of hepatic oxalate synthesis in humans, examine the association with other metabolic pathways and identify ways that oxalate synthesis may be modified. In addition, we suggest what is required for further progress in this area. MATERIALS AND METHODS: We consolidated relevant data primarily from recently published literature, considered new pharmacological approaches to decrease oxalate synthesis, and formulated an overview of the regulation and modification of oxalate synthesis pathways. RESULTS: Experiments with animals, including humans, animal cells and in vitro preparations of cellular components, support the existence of a major metabolic pathway linking the amino acids serine, glycine and alanine. Oxalate synthesis is a minor, secondary reaction of a cascade of reactions termed the glyoxylate pathway, which has a prominent role in gluconeogenesis and ureagenesis. The enzymatic steps and effectors which regulate glyoxylate and oxalate synthesis are not well characterized. Pharmacological approaches can reduce oxalate synthesis by diminishing the glyoxylate pool and possibly modifying enzymatic reactions leading to glyoxylate synthesis. CONCLUSIONS: The individual steps associated with glyoxylate and oxalate synthesis can be identified. The glyoxylate pathway has a significant functional role in intermediary liver metabolism but the way it is regulated is uncertain. Oxalate synthesis can be modified by drugs, indicating that primary and idiopathic hyperoxaluria may respond to pharmacological intervention.
PURPOSE: We define the major pathways of hepatic oxalate synthesis in humans, examine the association with other metabolic pathways and identify ways that oxalate synthesis may be modified. In addition, we suggest what is required for further progress in this area. MATERIALS AND METHODS: We consolidated relevant data primarily from recently published literature, considered new pharmacological approaches to decrease oxalate synthesis, and formulated an overview of the regulation and modification of oxalate synthesis pathways. RESULTS: Experiments with animals, including humans, animal cells and in vitro preparations of cellular components, support the existence of a major metabolic pathway linking the amino acids serine, glycine and alanine. Oxalate synthesis is a minor, secondary reaction of a cascade of reactions termed the glyoxylate pathway, which has a prominent role in gluconeogenesis and ureagenesis. The enzymatic steps and effectors which regulate glyoxylate and oxalate synthesis are not well characterized. Pharmacological approaches can reduce oxalate synthesis by diminishing the glyoxylate pool and possibly modifying enzymatic reactions leading to glyoxylate synthesis. CONCLUSIONS: The individual steps associated with glyoxylate and oxalate synthesis can be identified. The glyoxylate pathway has a significant functional role in intermediary liver metabolism but the way it is regulated is uncertain. Oxalate synthesis can be modified by drugs, indicating that primary and idiopathic hyperoxaluria may respond to pharmacological intervention.