GLYOXYLATE SYNTHESIS, AND ITS MODULATION AND INFLUENCE ON OXALATE SYNTHESIS

Purpose: We define the major pathways of hepatic oxalate synthesis in humans, examine the association with other metabolic pathways and iden tify ways that oxalate synthesis may be modified. In addition, we sugg est what is required for further progress in this area. Materials and Methods: We consolidated relevant data primarily from recently publish ed literature, considered new pharmacological approaches to decrease o xalate synthesis, and formulated an overview of the regulation and mod ification of oxalate synthesis pathways. Results: Experiments with ani mals, including humans, animal cells and in vitro preparations of cell ular components, support the existence of a major metabolic pathway li nking the amino acids serine, glycine and alanine. Oxalate synthesis i s a minor, secondary reaction of a cascade of reactions termed the gly oxylate pathway, which has a prominent role in gluconeogenesis and ure agenesis. The enzymatic steps and effecters which regulate glyoxylate and oxalate synthesis are not well characterized. Pharmacological appr oaches can reduce oxalate synthesis by diminishing the glyoxylate pool and possibly modifying enzymatic reactions leading to glyoxylate synt hesis. Conclusions: The individual steps associated with glyoxylate an d oxalate synthesis can be identified. The glyoxylate pathway has a si gnificant functional role in intermediary liver metabolism but the way it is regulated is uncertain. Oxalate synthesis can be modified by dr ugs, indicating that primary and idiopathic hyperoxaluria may respond to pharmacological intervention.