Conjugation with glycine

The major route of elimination is via the kidneys as the glycine conjugates, with more than 60% excreted as furoylglycine within the first 24 h after oral administration. Only 3-7% is excreted in the feces and less than 1% is excreted in expired air. The half-life of an oral dose is 2-2.5 h. 

T Kanazu, T Yamaguchi. Comparison of in vitro carnitine and glycine conjugation with branched-side chain and cyclic side chain carboxylic acids in rats. Drug Metab Dispos 25(2) 149—153, 1997. 

Figure 11.6 Meteor on-screen reasoning display showing the dependence of molecular weight and lipophilicity on the likelihood of glycine conjugation with carboxylic acids.

Human sensitization studies were negative at 10% solution (47). Undiluted benzyl alcohol produces moderate dermal irritation in guinea pigs and mild dermal irritation in rabbits (48,49). Severe eye irritation was noted in a rabbit study (50). Acute oral rat LD q values were reported between 1.23 and 3.10 g/kg (50—52). A dermal rabbit LD q value of 2.0 g/kg has been reported (49). Rats died after 2 h when exposed to a 200-ppm vapor concentration (53). Benzyl alcohol is readily oxidized in animals and humans to benzoic acid [65-85-0] which is then conjugated with glycine [56-40-6], and rapidly eliminated in the urine as hippuric acid [495-69-2] (54). 

FIGURE 25.41 Cholic acid, a bile salt, is synthesized from cholesterol via 7o -hydroxy-cholesterol. Conjugation with taurine or glycine produces taurocholic acid and glycocholic acid, respectively. Taurocholate and glycocholate are freely water-soluble and are highly effective detergents. 

Finally, the fact that anthocyanins can reach the brain represents a beginning of an explanation of the purported neuroprotection effects of anthocyanins. Anthocyanins may be eliminated via urinary and biliary excretion routes. " The extent of elimination of anthocyanins via urine is usually very low (< 0.2% intake) in rats and in humans, indicating either a more pronounced elimination via the bile route or extensive metabolism. As mentioned earlier, in the colon, non-absorbed or biliary excreted anthocyanins can be metabolized by the intestinal microflora into simpler break-down compounds such as phenolic acids that may be (re)absorbed and conjugated with glycine, glucuronic acid, or sulfate and also exhibit some biological... 

Elute the bound conjugate with 0.1 M glycine, 0.15M NaCl, pH 2.8, or another suitable elution buffer. A neutral pH alternative to this buffer is the Gentle Elution Buffer from Thermo Fisher. If acid pH conditions are used, immediately neutralize the fractions eluting from the column by the addition of 0.5 ml of 1M Tris, pH 8.0, per fraction. 

Cholic acid and chenodeoxycholic acid, known as the primary bile acids, are quantitatively the most important metabolites of cholesterol. After being biosynthesized, they are mostly activated with coenzyme A and then conjugated with glycine or the non-pro-teinogenic amino acid taurine (see p. 62). The acid amides formed in this way are known as conjugated bile acids or bile salts. They are even more amphipathic than the primary products. 

The biosynthesis of sulfate esters with the help of phosphoadenosine phosphosulfate (PAPS), the active sulfate , (see p. 110) and amide formation with glycine and glutamine also play a role in conjugation. For example, benzoic acid is conjugated with glycine to form the more soluble and less toxic hippuric acid (N-benzoylglycine see p. 324). 

Other components of the urine are conjugates with sulfuric acid, glucuronic acid, glycine, and other polar compounds that are synthesized in the liver by biotransformation (see p. 316). In addition, metabolites of many hormones (catecholamines, steroids, serotonin) also appear in the urine and can provide information about hormone production. The proteohormone chorionic gonadotropin (hCG, mass ca. 36 kDa), which is formed at the onset of pregnancy, appears in the urine due to its relatively small size. Evidence of hCG in the urine provides the basis for an immunological pregnancy test. 

Toluene exposure does not result in the hematopoietic effects caused by benzene. The myelotoxic effects previously attributed to toluene are judged by more recent investigations to be the result of concurrent exposure to benzene present as a contaminant in toluene solutions. Most of the toluene absorbed from inhalation is metabolized to benzoic acid, conjugated with glycine in the liver to form hippuric acid, and excreted in the urine. The average amount of hippuric acid excreted in the urine by persons not exposed to toluene is approximately 0.7-1.0 g/1 of urine. ... 

Other drugs are metabolised by Phase II synthetic reactions, catalysed typically by non-microsomal enzymes. Processes include acetylation, sulphation, glycine conjugation and methylation. Phase II reactions may be affected less frequently by ageing. Thus according to some studies, the elimination of isoniazid, rifampicin (rifampin), paracetamol (acetaminophen), valproic acid, salicylate, indomethacin, lorazepam, oxazepam, and temazepam is not altered with age. However, other studies have demonstrated a reduction in metabolism of lorazepam, paracetamol (acetaminophen), ketoprofen, naproxen, morphine, free valproic acid, and salicylate, indicating that the effect of age on conjugation reactions is variable. 

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