Conjugation of Benzoic Acid with Glycine in the Human Fetal
and Adult Liver and Kidney

Pacifici, Gian Maria; Mogavero, S; Giuliani, L.; Rane, Anders

doi:10.1159/000457499

Cited by 18 publications

(4 citation statements)

References 15 publications

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“…Furthermore, larger percentages of benzyl alcohol doses were found in urine as benzoic acid in preterm babies, while less hippuric acid appeared in their urine compared with term neonates. These results are consistent with those reported by Pacifici et al [140] which show that the rate of hippuric acid formation in the homogenates obtained from adult and mid-gestational fetal liver and kidney was respectively 42-and 44-fold higher in adult liver and kidney compared with fetal samples.…”

Section: Conjugation With Amino Acidssupporting

confidence: 93%

Drug metabolism and disposition in children

Benedetti

Baltes

2003

Fundamemntal Clinical Pharma

156

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Key factors undergoing maturational changes accounting for differences in drug metabolism and disposition in the pediatric population compared with adults are reviewed. Gastric and duodenal pH, gastric emptying time, intestinal transit time, bacterial colonization and probably P-glycoprotein are important factors for drug absorption, whereas key factors explaining differences in drug distribution between the pediatric population and adults are membrane permeability, plasma protein concentration and plasma protein characteristics, endogenous substances in plasma, total body and extracellular water, fat content, regional blood flow and probably P-glycoprotein, mainly that present in the gut, liver and brain. As far as drug metabolism is concerned, important differences have been found in the pediatric population compared with adults both for phase I enzymes [oxidative (e.g. cytochrome CYP3A7 vs. CYP3A4 and CYP1A2), reductive and hydrolytic enzymes] and phase II enzymes (e.g. N-methyltransferases and glucuronosyltransferases). Finally, key factors undergoing maturational changes accounting for differences in renal excretion in the pediatric population compared with adults are glomerular filtration and tubular secretion. It would be important to generate information on the developmental aspects of renal P-glycoprotein and of other renal transporters as done and still being done with the different isozymes involved in drug metabolism.

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Section: Conjugation With Amino Acidssupporting

confidence: 93%

Drug metabolism and disposition in children

Benedetti

Baltes

2003

Fundamemntal Clinical Pharma

156

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“…Regarding humans, as discussed above (Section 3.3.3), the GDS operates well in kidney, especially in the cortex (Pacifici et al, 1991). In the intact human subject, it is generally very difficult to recognize that a metabolic reaction occurs in the kidney.…”

Section: Pharmacological Consequences Of the Glycine Deportation Smentioning

confidence: 97%

“…Km values for these three tissues were 43.4±6.6 ( n = 26), 33.3 ±6.1 ( n = 5), and 34.7 ± 11.3 ( n = 5) mM, respectively. Similarly, the Vmax values were 204 ± 47.8, 199 ±40.7, and 24.2 ± 16.9 pmol/min/mg tissue, respectively (Pacifici et al, 1991). This would suggest that the GDS also operates in the kidney, in particular, in the renal cortex.…”

Section: The Glycine Deportation Systemmentioning

confidence: 99%

The glycine deportation system and its pharmacological consequences

Beyoğlu

Idle

2012

Pharmacology & Therapeutics

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“…An alternative interpretation of these findings is that PAGLN is formed from PAA in the kidney. HA is formed from BA in adult kidney and liver tissue in vitro at similar rates [18]. …”

Section: Amino Acids As Agents Of Conjugationmentioning

confidence: 99%

Dog bites man or man bites dog? The enigma of the amino acid conjugations

Beyoğlu

Smith

Idle

2012

Biochemical Pharmacology

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The proposition posed is that the value of amino acid conjugation to the organism is not, as in the traditional view, to use amino acids for the detoxication of aromatic acids. Rather, the converse is more likely, to use aromatic acids that originate from the diet and gut microbiota to assist in the regulation of body stores of amino acids, such as glycine, glutamate, and, in certain invertebrates, arginine, that are key neurotransmitters in the CNS. As such, the amino acid conjugations are not so much detoxication reactions, rather they are homeostatic and neuroregulatory processes. Experimental data have been culled in support of this hypothesis from a broad range of scientific and clinical literature. Such data include the low detoxication value of amino acid conjugations and the Janus nature of certain amino acids that are both neurotransmitters and apparent conjugating agents. Amino acid scavenging mechanisms in blood deplete brain amino acids. Amino acids glutamate and glycine when trafficked from brain are metabolized to conjugates of aromatic acids in hepatic mitochondria and then irreversibly excreted into urine. This process is used clinically to deplete excess nitrogen in cases of urea cycle enzymopathies through excretion of glycine or glutamine as their aromatic acid conjugates. Untoward effects of high-dose phenylacetic acid surround CNS toxicity. There appears to be a relationship between extent of glycine scavenging by benzoic acid and psychomotor function. Glycine and glutamine scavenging by conjugation with aromatic acids may have important psychosomatic consequences that link diet to health, wellbeing, and disease.

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Conjugation of Benzoic Acid with Glycine in the Human Fetal and Adult Liver and Kidney

Cited by 18 publications

References 15 publications

Drug metabolism and disposition in children

Drug metabolism and disposition in children

The glycine deportation system and its pharmacological consequences

Dog bites man or man bites dog? The enigma of the amino acid conjugations

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