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The biochemistry and toxicology of benzoic acid metabolism and its relationship to the elimination of waste nitrogen.

Pharmacology & therapeutics (1993-10-01)
G C Tremblay, I A Qureshi
ABSTRACT

Detoxification of sodium benzoate by elimination as a conjugate with glycine, a nonessential amino acid, provides a pathway for the disposal of waste nitrogen. Since 1979, sodium benzoate has been widely used in the therapeutic regimen to combat ammonia toxicity in patients born with genetic defects in the urea cycle. Although the clinical use of benzoate is associated with improved outcome, the search for biochemical evidence in support of the rationale for benzoate therapy has produced conflicting results. This review begins with an historical account leading to elucidation of the biochemistry of benzoate detoxification and early work indicating the potential utility of the pathway for elimination of waste nitrogen. An introduction to contemporary efforts at employing benzoate to treat hyperammonemia is followed by a detailed review of studies on benzoate metabolism and resultant toxic interactions with other major metabolic pathways. With this background, the several metabolic routes by which benzoate is thought to promote the disposal of waste nitrogen are then examined, followed by a consideration of alternative mechanisms by which benzoate might combat ammonia toxicity.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Benzoic acid, ACS reagent, ≥99.5%
Supelco
Benzoic acid, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Melting point standard 121-123°C, analytical standard
Supelco
Mettler-Toledo Calibration substance ME 18555, Benzoic acid, analytical standard, for the calibration of the thermosystem 900, traceable to primary standards (LGC)
Sigma-Aldrich
Benzoic acid, ≥99.5%, FCC, FG
Sigma-Aldrich
Benzoic acid, puriss. p.a., ACS reagent, reag. Ph. Eur., ≥99.9% (alkalimetric)
Supelco
Benzoic acid, certified reference material for titrimetry, certified by BAM, ≥99.5%
USP
Benzoic acid, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Benzoic acid, ReagentPlus®, 99%
Sigma-Aldrich
Benzoic acid, meets analytical specification of Ph. Eur., BP, USP, FCC, E210, 99.5-100.5% (alkalimetric)
Supelco
Benzoic acid, Standard for quantitative NMR, TraceCERT®
Supelco
Benzoic Acid Solution, certified reference material, 2000 μg/mL in methylene chloride
Sigma-Aldrich
Benzoic acid, natural, ≥99.5%, FCC, FG
Sigma-Aldrich
Benzoic acid, purified by sublimation, ≥99%
Supelco
SS Benzoic Acid, 2000 μg/mL in dichloromethane, analytical standard
Sigma-Aldrich
Benzoic acid, SAJ first grade, ≥99.5%
Benzoic acid, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Benzoic acid, SAJ special grade, ≥99.5%