Excretion of hippuric acid during sodium benzoate therapy in patients with hyperglycinaemia or hyperammonaemia

Barshop, Bruce A.; Breuer, Joseph; Holm, Jan; Leslie, Jack; Nyhan, William L.

doi:10.1007/bf01805533

Cited by 28 publications

(12 citation statements)

References 18 publications

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“…Theoretically, 1 mole of benzoate removes 1 mole of glycine as hippurate. In NKH patients, at least 75% of ingested benzoate is excreted as hippurate (Barshop et al 1989), and hippurate excretion is linearly related to the benzoate dose. The benzoate dose thus reflects the hippurate excretion.…”

Section: Methodsmentioning

confidence: 98%

Benzoate treatment and the glycine index in nonketotic hyperglycinaemia

Hove

Kerckhove

Hennermann

et al. 2004

J of Inher Metab Disea

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High-dose benzoate treatment aimed at reducing plasma glycine levels to normal reduces seizures and increases wakefulness in patients with nonketotic hyperglycinaemia (NKH). Since benzoate metabolism is dependent on the available glycine pool, and since the glycine pool is variably affected by the deficiency in the glycine cleavage enzyme system, we examined the importance of interpatient variability in benzoate requirement. To correct for the dietary glycine contribution, the glycine index was introduced as the molar requirement of benzoate dose necessary to normalize plasma glycine levels and subtracting from that the dietary glycine intake, both corrected for weight. The glycine index varied between 3.62 and 4.87 mmol/kg per day in five patients with a poor neurodevelopmental outcome and between 0.92 and 1.90 mmol/kg per day in four patients with a better neurodevelopmental outcome, and was 2.54 mmol/kg per day in a single patient with an intermediate outcome. The glycine index was stable over time within each patient. Exceeding the balance by either increasing food glycine intake or decreasing the benzoate dose resulted in increased glycine levels. Exceeding the glycine tolerance by increasing benzoate resulted in elevated and toxic levels of benzoate. The glycine index is a stable, individually specific parameter in patients with NKH. It has clinical consequences for the dose of benzoate required and the role of dietary management. Through its correlation with neurodevelopmental outcome, the glycine index points to potential genetic factors that could contribute to the psychomotor retardation in NKH.

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Section: Methodsmentioning

confidence: 98%

Benzoate treatment and the glycine index in nonketotic hyperglycinaemia

Hove

Kerckhove

Hennermann

et al. 2004

J of Inher Metab Disea

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show abstract

“…No effective treatment has been reported consistently. SB has been used in the treatment because it reacts with glycine to form hippurate, which is then excreted (12,13,20,26). Although benzoate doses as high as 3.5-5.2 mmol/kg/d (500 -750 mg/kg/d) (26) have been used, they were not without toxicity (20,28).…”

Section: Discussionmentioning

confidence: 99%

“…Concentrations of glycine are elevated in plasma and CSF. Oral administration of SB lowered CSF and plasma glycine in these patients accompanied with attenuation of seizures (11)(12)(13).…”

mentioning

confidence: 84%

Effect of Pantothenic Acid on Hippurate Formation in Sodium Benzoate-Treated HepG2 Cells

Palekar

2000

Pediatr Res

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“…The catalytic activity o f this enzyme is known to be modulat ed physiologically by hippurate [6,7], Hippurate (benzoylglycine) is, according to our present knowledge, a metabolic end prod uct excreted by the kidney. It is known to be synthesized in the liver and kidney of verte brates from benzoate and glycine [8], Its rate of synthesis is variable and is thought to depend ultimately on the availability o f benzoate [9], The significance o f this reaction is poorly un derstood. Also unknown is the physiological role of hippurate, apart from its above-men tioned effect on tubular ammoniagenesis.…”

Section: Introductionmentioning

confidence: 99%

Ammonia Production from Hippurate by the Rat Kidney in vitro

Mályusz¹,

Hackl²,

Wrigge³

et al. 1994

Kidney Blood Press Res

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Hippurate is known to be synthesized from benzoate and glycine in the liver and kidney. It takes part in renal ammoniagenesis by modulating the activity of γ-glutamyl transpeptidase (γGT). Due to its chemical structure, however, hippurate might also serve as a substrate of renal ammoniagenesis. Hippurate may yield ammonia either having been cleaved by hippuricase or by Erlenmeyer’s reaction after condensation with an aldehyde. In order to elucidate the possibility of hippurate being a substrate of renal ammoniagenesis, experiments were carried out on cortical kidney slices and on isolated tubular segments of the rat. The incubation medium (pH 7.1) was enriched with 10 mmol/l hippurate spiked with ^l5N-hippurate, some of the known competitive inhibitors of hippuricase, acivicin and different aldehydes. Factors known to affect hippuricase or γGT did not interfere with renal ammonia production. Glyceraldehyde (up to 1.0 mmol/l) but not glycerate had a stimulating effect, especially on the ammoniagenesis from hippurate. In normal rats fed a vegetarian diet, 1% of the added ¹⁵N moiety was found to be ¹⁵NH₃. Renal ^l5NH₃ production was significantly greater if, prior to the experiments, the animals were either acidotic or had a reduced renal mass or were fed animal proteins. These results indicate that hippurate may, to a certain extent, serve as substrate for ammoniagenesis.

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Excretion of hippuric acid during sodium benzoate therapy in patients with hyperglycinaemia or hyperammonaemia

Cited by 28 publications

References 18 publications

Benzoate treatment and the glycine index in nonketotic hyperglycinaemia

Benzoate treatment and the glycine index in nonketotic hyperglycinaemia

Effect of Pantothenic Acid on Hippurate Formation in Sodium Benzoate-Treated HepG2 Cells

Ammonia Production from Hippurate by the Rat Kidney in vitro

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