The glycine deportation system and its pharmacological consequences

Beyoğlu, Diren; Idle, Jeffrey R.

doi:10.1016/j.pharmthera.2012.05.003

Cited by 51 publications

(73 citation statements)

References 151 publications

(194 reference statements)

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“…While hippurate in the diet can be converted back to benzoate by gut microbes, the hippurate synthesis in the liver and kidneys is irreversible and critically dependent on mitochondrial function (Beyoglu and Idle 2012). Mitochondria provide most of the energy for liver cell function via oxidative phosphorylation fed by the tricarboxylic acid cycle and β oxidation of long-chain fatty acids.…”

Section: Actions Of Sorbate and Benzoate Preservatives On Mitochondriamentioning

confidence: 99%

“…Benzoate accumulates in the matrix of liver and kidney mitochondria to about 50-fold over its extra-mitochondrial concentration (Gatley and Sherratt 1977), where it is conjugated with glycine-the most abundant free amino acid in the adult human liver. It is thereby converted to hippurate, a compound that can be efficiently removed from the body by the kidneys (Gatley and Sherratt 1977;Beyoglu and Idle 2012). This process acts not only as a mechanism of detoxification, increasing the water solubility of this organic acid in order to facilitate its urinary excretion, but also as a means of regulating systemic levels of amino acids utilized as neurotransmitters in the central nervous system (Badenhorst and others 2014).…”

Section: Use Of Sb In the Clinical Treatment Of Patients With Ucds Anmentioning

confidence: 99%

“…Hyperammonemia sometimes arises as the consequence of drug therapy (Beyoglu and Idle 2012). It can result during intravenous therapy with asparaginase, a standard treatment for acute lymphoblastic leukemia and non-Hodgkin lymphoma in childhood, whereupon it, in turn, can be counteracted by a therapy consisting of protein restriction, together with the administration of SB and glucose/insulin (Jörck and others 2011).…”

Section: Use Of Sb In the Clinical Treatment Of Patients With Ucds Anmentioning

confidence: 99%

“…The often fatal disorder Reye's syndrome, mentioned above in connection with MPT, is also associated with hyperammonemia (Trost and Lemasters 1996). This condition of liver mitochondrial dysfunction is severely aggravated by salicylates (Glasgow 2006), which are-like benzoate-substantially metabolized through their conjugation with glycine (to form salicylglycine, or salicyluric acid (Beyoglu and Idle 2012)). …”

Section: Use Of Sb In the Clinical Treatment Of Patients With Ucds Anmentioning

confidence: 99%

“…Second, as discussed later, there is an ever-increasing need to evaluate the safety of sodium benzoate (SB) in view of a rapidly expanding body of medical research, which indicates that this compound may provide inexpensive therapy for a number of diseases, in addition to its well-established use in the treatment of urea cycle disorders (UCDs). It is important to appreciate that a low exposure to benzoate will be inevitable for most individuals, as this is a compound that is both generated by the actions of our gut microbes (Beyoglu and Idle 2012) and present-usually in relatively low concentrations <40 mg/kg-in many berries and milk products Barceloux 2009a, 2009b;Vandevijvere and others 2009). Benzoate can arise from the hippuric acid naturally occurring in milk at concentrations of up to 50 mg/kg, and forms during cheese ripening (Sieber and others 1995).…”

Section: Introductionmentioning

confidence: 99%

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Benzoate and Sorbate Salts: A Systematic Review of the Potential Hazards of These Invaluable Preservatives and the Expanding Spectrum of Clinical Uses for Sodium Benzoate

Piper

2017

Comprehensive Reviews in Food Science and Food Safety

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Sodium benzoate and potassium sorbate are extremely useful agents for food and beverage preservation, yet concerns remain over their complete safety. Benzoate can react with the ascorbic acid in drinks to produce the carcinogen benzene. A few children develop allergy to this additive while, as a competitive inhibitor of D-amino acid oxidase, benzoate can also influence neurotransmission and cognitive functioning. Model organism and cell culture studies have raised some issues. Benzoate has been found to exert teratogenic and neurotoxic effects on zebrafish embryos. In addition, benzoate and sorbate are reported to cause chromosome aberrations in cultured human lymphocytes; also to be potently mutagenic toward the mitochondrial DNA in aerobic yeast cells. Whether the substantial human consumption of these compounds could significantly increase levels of such damages in man is still unclear. There is no firm evidence that it is a risk factor in type 2 diabetes. The clinical administration of sodium benzoate is of proven benefit for many patients with urea cycle disorders, while recent studies indicate it may also be advantageous in the treatment of multiple sclerosis, schizophrenia, early-stage Alzheimer's disease and Parkinson's disease. Nevertheless, exposure to high amounts of this agent should be approached with caution, especially since it has the potential to generate a shortage of glycine which, in turn, can negatively influence brain neurochemistry. We discuss here how a small fraction of the population might be rendered-either through their genes or a chronic medical condition-particularly susceptible to any adverse effects of sodium benzoate.

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The glycine deportation system and its pharmacological consequences

Cited by 51 publications

References 151 publications

Benzoate and Sorbate Salts: A Systematic Review of the Potential Hazards of These Invaluable Preservatives and the Expanding Spectrum of Clinical Uses for Sodium Benzoate

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