Glycine and Aspirin Metabolism: The Salicyluric Acid Pathway

Table of Contents

1. Overview: Why Glycine Matters for Aspirin
2. Step 1: Aspirin → Salicylate
3. Step 2: Salicylate → Salicyluric Acid
4. The GLYAT Enzyme
5. Does Glycine Supply Limit the Pathway?
6. Aspirin Overdose and Glycine Depletion
7. The Reye's Syndrome Connection
8. Genetic Variation in GLYAT
9. Salicylate's Nonlinear Pharmacokinetics
10. Alternative Disposal Pathways
11. Cofactors: CoA, ATP, and Pyridoxal Phosphate
12. Other Drugs Cleared by Glycine Conjugation
13. Low-Dose and Regular Aspirin Use
14. Collagen-Rich Foods and Glycine
15. Salicyluric Acid as a Urinary Marker
16. Key Points
17. Key Research Papers
18. Connections
19. Featured Videos

Overview: Why Glycine Matters for Aspirin

Aspirin (chemical name acetylsalicylic acid) is one of the most widely used medicines, taken at low daily doses (such as 75 or 81 mg) for cardiovascular prevention and at higher doses for pain, fever and inflammation. Part of its disposal depends on glycine, a conditionally essential amino acid that is abundant in collagen, gelatin and bone broth.

Glycine does not act on aspirin itself. Aspirin is first hydrolyzed by esterases into salicylic acid (salicylate), which carries most of aspirin's anti-inflammatory and pain-relieving action. Salicylate is then joined to glycine to form salicyluric acid, joined to glucuronic acid, oxidized to gentisic acid, or excreted unchanged (Needs and Brooks 1985). In 45 volunteers given a 600 mg dose, salicyluric acid made up 75% of the urinary metabolites (Patel, Hesse et al. 1990); in 10 volunteers it was 63% of the dose recovered over 8 hours (Patel, Notarianni and Bennett 1990); and in 129 volunteers given 900 mg it was the main metabolite in most people, ranging from 19.8% to 65% of the dose (Hutt 1986).

The glycine reaction is catalyzed by glycine N-acyltransferase (GLYAT), an enzyme of liver and kidney mitochondria (Matsuo 2012). The formation of salicyluric acid saturates at fairly low salicylate concentrations and follows Michaelis-Menten kinetics, so salicylate's half-life lengthens as the dose rises (Needs and Brooks 1985). In overdose patients the share of salicylate leaving as salicyluric acid fell as plasma salicylate rose — the authors called this the progressive saturation of salicyluric acid formation at toxic doses (Patel, Hesse et al. 1990) — and plasma glycine was lower than in healthy volunteers (Patel, Ogunbona et al. 1990).

The research therefore covers three settings unevenly: the low-dose daily user, the person taking high anti-inflammatory doses, and the overdose patient. Most of the glycine-specific evidence comes from the overdose setting. No study cited on this page tested whether glycine intake changes salicylate levels in people who take aspirin regularly.

Step 1: Aspirin → Salicylate

The first thing that happens to swallowed aspirin is hydrolysis — removal of the acetyl group from the salicylate backbone. Needs and Brooks (1985) describe absorption with a half-life of 5 to 16 minutes, hydrolysis by nonspecific esterases mainly in the liver and to a lesser extent the stomach, so that about 68% of a dose reaches the circulation as intact aspirin, and a serum half-life of aspirin of about 20 minutes. Aspirin can also irreversibly acetylate many proteins, including serum albumin.

Aspirin's distinctive action — irreversible acetylation of platelet cyclooxygenase-1, which lasts for the remaining life of each platelet — happens during this brief window. After that, the circulating drug is salicylate, whose concentration rises as aspirin's falls (Needs and Brooks 1985).

This distinction matters because salicylate, not aspirin, is what the liver and kidneys mostly handle. Glycine conjugation, glucuronidation and renal excretion all act on salicylate. From this point on, “aspirin metabolism” on this page means salicylate metabolism.

Step 2: Salicylate → Salicyluric Acid

Salicylic acid is a weak acid. Part of it is excreted unchanged by the kidney, and the rate depends on urinary pH, urine flow and the presence of other organic acids (Needs and Brooks 1985); more is excreted when the urine is alkaline (Proudfoot 2004). The rest is converted by the liver into more water-soluble products. In the 129-volunteer study (900 mg dose, urine collected over 12 hours; Hutt 1986):

1. Glycine conjugation — salicylate is activated to an acyl-coenzyme A thioester and then joined to glycine, forming salicyluric acid (2-hydroxyhippuric acid). It was the major metabolite in most volunteers, ranging from 19.8% to 65% of the dose.
2. Glucuronic acid conjugation — the acyl and phenolic glucuronides of salicylate together ranged from 0.8% to 42% of the dose, and their excretion was inversely related to that of salicyluric acid.

Unchanged salicylic acid ranged from 1.3% to 31% of the dose and was related to urine volume and pH. Gentisic acid (about 1%) and salicyluric acid phenolic glucuronide (about 3%) were minor metabolites (Hutt 1986).

The glycine conjugation reaction takes place in two steps inside mitochondria (Knights 2007):

1. Activation. Salicylate is joined to coenzyme A (CoA), forming salicyl-CoA. Like other acyl-CoA synthetase reactions, this step uses ATP.
2. Conjugation. GLYAT transfers the salicyl group from CoA onto glycine, releasing free CoA and producing salicyluric acid.

Salicyluric acid then leaves the liver and is excreted in the urine.

The GLYAT Enzyme

Glycine N-acyltransferase is encoded by the GLYAT gene on human chromosome 11q12.1 (NCBI Gene). Matsuo and colleagues (2012) isolated human GLYAT and two related genes, GLYATL1 and GLYATL2, encoding proteins of 295, 302 and 294 amino acids. GLYAT joined glycine to benzoyl-CoA, while GLYATL1 joined glutamine to phenylacetyl-CoA; GLYAT was expressed specifically in the liver and kidney and located in mitochondria.

GLYAT handles a range of acyl-CoA substrates, among them:

• Benzoic acid (a food preservative), conjugated to hippuric acid — the reaction Armand Quick studied in his 1931 work on benzoic acid conjugation in man (Quick 1931)
• Salicylic acid (from aspirin and other salicylates), conjugated to salicyluric acid (van der Sluis 2013)
• Isovaleric acid and other endogenous organic acids, which makes GLYAT relevant to the management of organic acidemias (Badenhorst 2012)

Badenhorst and colleagues (2013) describe glycine conjugation as a pathway that keeps free coenzyme A available, and note that GLYAT activity affects mitochondrial ATP production, glycine availability, CoA availability and the toxicity of various organic acids.

Earlier studies described GLYAT kinetics as a random bi-bi and/or ping-pong mechanism. A 2017 study of the recombinant human enzyme found instead a sigmoidal curve when benzoyl-CoA was varied and substrate inhibition when glycine was varied, and concluded that human GLYAT shows kinetic cooperativity rather than simple Michaelis-Menten behaviour (van der Sluis 2017). Michaelis constants for benzoyl-CoA and glycine have been measured for the bovine enzyme (Badenhorst 2012). None of the sources on this page compares a human glycine Michaelis constant with measured glycine concentrations in liver mitochondria, so whether glycine supply limits the reaction at ordinary aspirin doses has not been shown.

Does Glycine Supply Limit the Pathway?

The clearest evidence comes from overdose. Patients with aspirin overdose had consistently lower plasma glycine than healthy volunteers, and oral glycine raised plasma glycine and the maximum rate of salicyluric acid excretion, although it did not change the fraction of salicylate recovered as salicyluric acid (Patel, Ogunbona et al. 1990). In the same study, a single therapeutic 500 mg dose did not change plasma glycine in healthy volunteers. Other factors that have been studied:

• The body's glycine budget. From reported production and consumption fluxes, Meléndez-Hevia and colleagues (2009) estimated that a 70 kg adult makes about 3 g of glycine a day (more than 85% of it from serine) and gets 1.5 to 3 g from the diet, and that this may fall about 10 g a day short of the amount needed for all uses, including collagen synthesis. This is a calculation from published fluxes, not a measured deficiency, and it did not look at drug conjugation.
• Dietary protein (animal study). In rats fed a 5% protein diet for 3 weeks, kidney mitochondrial preparations formed more salicyluric acid, urinary salicyluric acid rose, and salicylate was cleared faster at high doses than in rats on a 21% protein diet (Yue 1982) — the opposite of what a simple glycine-shortage model would predict. No equivalent human study is cited here.
• Aging. In a study of 8 older and 8 younger adults, the older group had lower red-cell glycine and glutathione, and 2 weeks of cysteine plus glycine raised glutathione (Sekhar 2011). An independent randomized trial in 114 healthy older adults found that glycine plus N-acetylcysteine did not raise glutathione, its primary endpoint (Lizzo 2022). Neither study measured salicylate.
• Competing substrates. Amsel and Levy (1969) studied the simultaneous glycine conjugation of benzoic and salicylic acids in people, as both use the same pathway.

Whether diet, illness, pregnancy or age changes how fast people clear salicylate through glycine conjugation has not been tested in the human studies cited on this page.

Aspirin Overdose and Glycine Depletion

The overdose studies give the most direct human data on the glycine pathway under load:

1. The salicyluric acid share falls as the dose rises. Patel and colleagues measured urinary metabolites in 45 volunteers given 600 mg of aspirin and in 37 overdose patients. Salicyluric acid was 75.0% of urinary metabolites in volunteers, 46.7% in 24 patients with admission plasma salicylate of 240–360 mg/L, and 21.6% in 13 patients with 715–870 mg/L; unchanged salicylic acid rose from 8.8% to 31.9% and 64.7%. The authors described this as the progressive saturation of salicyluric acid formation as aspirin load rises to toxic amounts, and raised questions about the glycine pool in overdose (Patel, Hesse et al. 1990).
2. Plasma glycine falls. In 45 overdose patients, plasma glycine was consistently lower than in healthy volunteers, which the authors took as a sign of depleted available glycine (Patel, Ogunbona et al. 1990).
3. Other routes compensate only partly in people. In 9 overdose patients, salicyluric acid fell to 30.0% of the recovered dose (against 63.1% in volunteers), with more salicylic acid, salicyl acyl glucuronide and gentisuric acid. Rats relied less on salicyluric acid and compensated through other routes; in people, compensation was incomplete (Patel, Notarianni and Bennett 1990).
4. Half-life lengthens. The serum half-life of salicylate is dose-dependent (Needs and Brooks 1985).
5. Urine alkalinization. The joint position paper of the American Academy of Clinical Toxicology and the European Association of Poisons Centres and Clinical Toxicologists describes urine alkalinization as intravenous sodium bicarbonate given to reach a urine pH of 7.5 or higher, and states that it should be considered first-line treatment for moderately severe salicylate poisoning in patients who do not meet the criteria for hemodialysis (Proudfoot 2004).

Glycine itself has been tested as an add-on in one study of overdose patients: oral glycine or N-glycylglycine raised plasma glycine and the peak rate of salicyluric acid excretion, but not the share of salicylate excreted as salicyluric acid (Patel, Ogunbona et al. 1990). The sources on this page report no larger trial.

The Reye's Syndrome Connection

Reye's syndrome is a rare, serious illness of encephalopathy with fatty degeneration of the liver, usually after influenza or varicella (Belay 1999). During an influenza A outbreak, Starko and colleagues (1980) found that all 7 children with Reye's syndrome had taken salicylate, against 8 of 16 ill classmate controls; the patients took larger doses, and salicylate consumption correlated with severity. In US national surveillance, reported cases in children peaked at 555 in 1980, after which warnings about salicylates in children with these infections were issued; there were no more than 36 cases a year from 1987 to 1997, and the case fatality rate over the whole period was 31% (Belay 1999).

Laboratory work points to the mitochondria. In skin fibroblasts from 8 patients who had had Reye's syndrome, Glasgow and colleagues (1999) found no inherited defect of β-oxidation. The aspirin metabolites salicylate, hydroxyhippurate (salicyluric acid) and gentisate — but not aspirin itself — reversibly inhibited fatty-acid oxidation, acting on the long-chain 3-hydroxyacyl-CoA dehydrogenase step of the mitochondrial trifunctional enzyme, and the patients' cells were more sensitive than control cells at 0.5 to 5 mM salicylate. Note that in this work salicyluric acid, the glycine conjugate, was itself one of the inhibitors.

Reviews of glycine conjugation note that acyl-CoA thioesters that are not conjugated can disturb mitochondrial function, and that glycine conjugation helps keep free CoA available (Knights 2007; Badenhorst 2013). Whether glycine status affects the risk of Reye's syndrome has not been studied in the sources cited here. Because the syndrome is now very rare, Belay and colleagues (1999) write that any child suspected of having it should be investigated for the treatable inborn metabolic disorders that can mimic it.

What the research and warnings say: Glasgow (2006) argues that the evidence links Reye's syndrome causally to aspirin taken during the febrile illness in children and teenagers under 18, that aspirin appears to act as a co-factor in susceptible individuals, and that in the presence of a viral infection no dose of aspirin can be considered safe. Government health warnings on aspirin-containing products followed the early-1980s findings, and case numbers declined sharply afterwards (Belay 1999; Glasgow 2006). Willow bark is a plant source of salicylates, which enter the same disposal pathway.

Genetic Variation in GLYAT

People differ widely in how much of an aspirin dose they excrete as salicyluric acid: 19.8% to 65% of a 900 mg dose in 129 healthy volunteers, with glucuronide excretion moving in the opposite direction (Hutt 1986). Caldwell and colleagues reported inter-individual differences in the glycine conjugation of salicylic acid as early as 1980 (Caldwell 1980). Some of this variation may be genetic:

• Enzyme variants in the laboratory. Van der Sluis and colleagues (2013) made six variants of recombinant human GLYAT. The K16N, S17T and R131H variants had activity similar to the reference enzyme, the N156S variant was more active, the F168L variant was less active, and the R199C variant was inactive.
• Variant frequencies. In data from 1,537 people, the two most common GLYAT haplotypes were S156 (70%) and T17S156 (20%); the S156C199 and S156H131 haplotypes, which lower enzyme activity, were found at very low frequencies, and a new Q61L variant was found at 12% in a South African Afrikaner cohort. The authors concluded that the GLYAT coding region is highly conserved, consistent with glycine conjugation being an essential detoxification pathway (van der Sluis 2015).

The authors suggest these variants may explain some of the differences in glycine conjugation capacity relevant to aspirin metabolism (van der Sluis 2013). The studies cited here did not measure aspirin disposal in people carrying the variants.

Salicylate's Nonlinear Pharmacokinetics

Salicylate is a classic example of a drug with capacity-limited (Michaelis-Menten) elimination, described in man by Levy (1965). Needs and Brooks (1985) summarize the pattern: the formation of salicyluric acid and of salicyl phenolic glucuronide is easily saturated at low salicylic acid concentrations and follows Michaelis-Menten kinetics, while the other metabolic routes follow first-order kinetics. As a result the serum half-life of salicylate depends on dose, and the larger the dose, the longer it takes to reach steady state. They also note evidence that salicyluric acid formation can be induced.

Because the main routes saturate, the plasma salicylate level rises more than in proportion to the dose once those routes fill — the capacity-limited pattern Levy (1965) described.

Needs and Brooks (1985) also report no significant differences in salicylate pharmacokinetics in the elderly or in children compared with young adults, and essentially the same parameters in rheumatoid arthritis, osteoarthritis, chronic renal failure and liver disease, apart from differences in free versus albumin-bound salicylate.

Alternative Disposal Pathways

When glycine conjugation fills up, more salicylate leaves by other routes (Hutt 1986; Patel, Hesse et al. 1990):

1. Phenolic glucuronidation. The phenolic hydroxyl group of salicylate is joined to glucuronic acid, forming salicyl phenolic glucuronide.
2. Acyl glucuronidation. The carboxyl group of salicylate is joined to glucuronic acid, forming the acyl (ester) glucuronide.
3. Renal excretion of unchanged salicylate. Salicylic acid is a weak acid (pK_a about 3); its excretion depends on urinary pH and flow (Needs and Brooks 1985), and urine alkalinization increases it (Proudfoot 2004).
4. Oxidation to gentisic acid (2,5-dihydroxybenzoic acid), a minor route — about 1% of a 900 mg dose (Hutt 1986).

In overdose patients, more of the dose appeared as gentisic acid and salicylic acid phenolic glucuronide; the authors read this as evidence that these processes were not saturated, and estimated that they handled 22% to 23% of large doses (Patel, Hesse et al. 1990). In people, compensation by these routes was incomplete (Patel, Notarianni and Bennett 1990).

Cofactors: CoA, ATP, and Pyridoxal Phosphate

Glycine is not the only factor the pathway needs:

• Coenzyme A (CoA). Each salicylate molecule is first bound to CoA. Reviews describe glycine conjugation as a way of releasing that CoA again, and note that acyl-CoA thioesters that are not conjugated can disturb mitochondrial function (Knights 2007; Badenhorst 2013).
• ATP. The activation step uses ATP, and GLYAT activity affects mitochondrial ATP production (Badenhorst 2013).
• Pyridoxal-5-phosphate (active vitamin B6) and folate. Most of the body's glycine is made from serine (Meléndez-Hevia 2009) by serine hydroxymethyltransferase, an enzyme that uses pyridoxal phosphate and a folate cofactor. The amount produced is limited to no more than the amount of one-carbon units the reaction generates (Meléndez-Hevia 2009).

None of the studies cited here tested whether vitamin B6, folate or other nutrients change salicylate disposal in people.

Other Drugs and Compounds Cleared by Glycine Conjugation

Salicylate is the best-known drug cleared by glycine conjugation, and Knights and colleagues (2007) note that relatively few xenobiotic carboxylic acids use the route. Other compounds handled by GLYAT include:

• Benzoate — a food preservative, conjugated to hippuric acid (Quick 1931; van der Sluis 2015). Benzoate conjugation is also relevant to the treatment of some metabolic disorders (van der Sluis 2013).
• Xylene — the industrial solvent, whose metabolism also relies on glycine conjugation (van der Sluis 2013).
• Isovaleric acid and other organic acids — endogenous acids that build up in organic acidemias (Badenhorst 2012).

Not every acyl-CoA is a GLYAT substrate: in the human enzyme family, GLYATL1 joined phenylacetyl-CoA to glutamine rather than glycine (Matsuo 2012). Salicylate also comes from food: salicylic acid was found in the serum of every person tested who was not taking aspirin, at higher levels in vegetarians than in non-vegetarians (median 0.11 vs 0.07 µmol/L), against a median of 10.03 µmol/L in patients taking 75 mg of aspirin a day, with some overlap between vegetarians and aspirin users (Blacklock 2001). Amsel and Levy (1969) studied what happens when benzoic and salicylic acids are conjugated with glycine at the same time.

Low-Dose and Regular Aspirin Use

Most people who take aspirin long-term are on a low daily dose (75 or 81 mg). What the research shows for this group:

• Patients taking 75 mg a day had a median serum salicylic acid of 10.03 µmol/L (range 0.23–25.40), far higher than in people not taking aspirin (Blacklock 2001).
• In healthy volunteers, a single therapeutic 500 mg dose did not change plasma glycine (Patel, Ogunbona et al. 1990).
• No study cited here measured glycine status in long-term low-dose users, or tested whether extra glycine changes their salicylate levels.

At the higher daily doses used historically for inflammatory conditions, salicylate kinetics become dose-dependent as the glycine and phenolic glucuronide routes saturate (Needs and Brooks 1985). Whether glycine intake changes salicylate levels at these doses has not been tested in the studies cited on this page; the only human data on added glycine come from overdose patients (Patel, Ogunbona et al. 1990).

Collagen-Rich Foods and Glycine

Glycine occupies every third position in the collagen triple helix, so collagen-rich foods are among the richest dietary sources. They include:

• Bone broth — long-simmered bones release gelatin, which is partially hydrolyzed collagen. The glycine content varies with the bones and the cooking.
• Gelatin — the cooked form of collagen used in traditional jellies and set desserts.
• Hydrolyzed collagen peptides — the same amino-acid profile in a form that dissolves in cold liquids.
• Skin-on poultry, oxtail, shank, hocks and other connective-tissue cuts — whole-animal eating includes the tissues that muscle-meat-only diets leave out.
• Free glycine — a sweet-tasting, water-soluble powder. Sleep studies have given 3 g before bedtime (see the main Glycine page).

No study cited on this page tested whether collagen-rich foods or glycine supplements change how people taking aspirin clear salicylate. Questions about medicines and supplements belong with a clinician.

Salicyluric Acid as a Urinary Marker

Because salicyluric acid comes from salicylate, urinary salicyluric acid reflects salicylate exposure, whether from medicines or from food (salicylic acid is present in the blood even of people not taking aspirin; Blacklock 2001).

In research, the amount of salicyluric acid excreted after a standard aspirin dose, relative to the other metabolites, has been used to describe how individuals differ in glycine conjugation (Caldwell 1980; Hutt 1986; Patel, Hesse et al. 1990). It is not part of routine clinical chemistry.

Key Points

1. Glycine conjugation is the main route for salicylate at therapeutic doses. Salicyluric acid was 63% to 75% of urinary output in two volunteer studies, and ranged from 19.8% to 65% of the dose across 129 volunteers (Patel, Hesse et al. 1990; Patel, Notarianni and Bennett 1990; Hutt 1986).
2. The route saturates. Its share fell to about 22% in overdose patients with the highest plasma salicylate, described as progressive saturation at toxic doses (Patel, Hesse et al. 1990).
3. Overdose patients had lower plasma glycine, and oral glycine raised the peak rate of salicyluric acid excretion in one study, without changing the share excreted that way (Patel, Ogunbona et al. 1990).
4. A single 500 mg dose did not change plasma glycine in healthy volunteers, and no cited study tested glycine intake in regular aspirin users (Patel, Ogunbona et al. 1990).
5. Urine alkalinization is described by a joint toxicology position paper as first-line treatment for moderately severe salicylate poisoning not meeting hemodialysis criteria (Proudfoot 2004).
6. Reye's syndrome is linked to aspirin use in children with viral illness; in cell studies salicylate and salicyluric acid inhibited mitochondrial fatty-acid oxidation (Starko 1980; Glasgow 1999; Glasgow 2006).
7. GLYAT variants differ in activity in the laboratory, but their effect on aspirin disposal in people has not been measured (van der Sluis 2013; van der Sluis 2015).

Key Research Papers

Peer-reviewed primary literature on glycine conjugation, the GLYAT enzyme, salicylate pharmacokinetics, and the clinical implications of glycine availability for aspirin metabolism. Each citation links to the full text via DOI or PubMed where available.

1. Levy G. Pharmacokinetics of salicylate elimination in man. Journal of Pharmaceutical Sciences. 1965;54(7):959–967. — doi:10.1002/jps.2600540703
2. Forman WB, Davidson ED, Webster LT Jr. Enzymatic conversion of salicylate to salicylurate. Molecular Pharmacology. 1971;7(3):247–259. — PubMed PMID: 5571642
3. Hutt AJ, Caldwell J, Smith RL. The metabolism of aspirin in man: a population study. Xenobiotica. 1986;16(3):239–249. — doi:10.3109/00498258609043527
4. Patel DK, Hesse A, Ogunbona A, Notarianni LJ, Bennett PN. Metabolism of aspirin after therapeutic and toxic doses. Human & Experimental Toxicology. 1990;9(3):131–136. — doi:10.1177/096032719000900302
5. Patel DK, Notarianni LJ, Bennett PN. Comparative metabolism of high doses of aspirin in man and rat. Xenobiotica. 1990;20(8):847–854. — doi:10.3109/00498259009046898
6. Knights KM, Sykes MJ, Miners JO. Amino acid conjugation: contribution to the metabolism and toxicity of xenobiotic carboxylic acids. Expert Opinion on Drug Metabolism & Toxicology. 2007;3(2):159–168. — doi:10.1517/17425255.3.2.159
7. Badenhorst CPS, van der Sluis R, Erasmus E, van Dijk AA. Glycine conjugation: importance in metabolism, the role of glycine N-acyltransferase, and factors that influence interindividual variation. Expert Opinion on Drug Metabolism & Toxicology. 2013;9(9):1139–1153. — doi:10.1517/17425255.2013.796929
8. van der Sluis R, Badenhorst CPS, Erasmus E, van Dyk E, van der Westhuizen FH, van Dijk AA. Conservation of the coding regions of the glycine N-acyltransferase gene further suggests that glycine conjugation is an essential detoxification pathway. Gene. 2015;571(1):126–134. — doi:10.1016/j.gene.2015.06.081
9. Glasgow JFT. Reye's syndrome: the case for a causal link with aspirin. Drug Safety. 2006;29(12):1111–1121. — doi:10.2165/00002018-200629120-00003
10. Bartels M, Brade AM, Reid TM, et al. Glycine N-acyltransferase: characterization of the recombinant human enzyme. Drug Metabolism and Disposition. — PubMed PMID: 23237781 (Editorial note, 2026-10-14: no paper matching this entry was found in PubMed or Crossref; nothing on this page rests on it, and the link is a PubMed topic search.)
11. Quick AJ. The conjugation of benzoic acid in man. Journal of Biological Chemistry. 1931;92(1):65–85. — doi:10.1016/s0021-9258(18)76545-9
12. Caldwell J, O'Gorman J, Smith RL. Inter-individual differences in the glycine conjugation of salicylic acid [proceedings]. British Journal of Clinical Pharmacology. 1980;9(1):114P. — doi:10.1111/j.1365-2125.1980.tb04816.x
13. Furst SM, Luedke D, Gandolfi AJ. Kinetic optimization of the conjugation of mercapturic acid intermediates with salicylate by hepatic glycine N-acyltransferase. Toxicology Letters. 1997;90(2–3):157–164. — Find on PubMed (Editorial note, 2026-10-14: no paper matching this entry was found in PubMed or Crossref; nothing on this page rests on it.)
14. Lehmann D, Nelsestuen GL. The amino acid sequence of human liver glycine N-acyltransferase. FEBS Letters. — Search PubMed (Editorial note, 2026-10-14: no paper matching this entry was found in PubMed or Crossref; nothing on this page rests on it.)
15. Nandi DL, Lucas SV, Webster LT Jr. Benzoyl-coenzyme A:glycine N-acyltransferase and phenylacetyl-coenzyme A:glycine N-acyltransferase from bovine liver mitochondria. Purification and characterization. Journal of Biological Chemistry. 1979;254(15):7230–7237. — doi:10.1016/s0021-9258(18)50309-4
16. Schachter D, Taggart JV. Benzoyl coenzyme A and hippurate synthesis. Journal of Biological Chemistry. 1953;203(2):925–934. — doi:10.1016/s0021-9258(19)52362-6
17. Starko KM, Ray CG, Dominguez LB, Stromberg WL, Woodall DF. Reye's syndrome and salicylate use. Pediatrics. 1980;66(6):859–864. — PubMed PMID: 7454476
18. Glasgow JFT, Middleton B. Reye syndrome — insights on causation and prognosis. Archives of Disease in Childhood. 2001;85(5):351–353. — doi:10.1136/adc.85.5.351
19. Beutler E, Larsh SE, Gurney CW. Iron therapy in chronically fatigued, nonanemic women: a double-blind study. Annals of Internal Medicine. 1960;52(2):378–394. — doi:10.7326/0003-4819-52-2-378 (Editorial note, 2026-10-14: a study of iron therapy, unrelated to aspirin or glycine; nothing on this page rests on it.)
20. Mehlman MA, Tobin RB. Comparison of the effects of dietary protein and salicylate on the urinary excretion of organic acids in rats. Journal of Nutrition. 1964;82(1):99–105. (Editorial note, 2026-10-14: the DOI previously given here resolves to an unrelated paper on vitamin A absorption in poultry, and no paper matching this entry was found in PubMed or Crossref; the link was removed and nothing on this page rests on it.)
21. Patel DK, Ogunbona A, Notarianni LJ, Bennett PN. Depletion of plasma glycine and effect of glycine by mouth on salicylate metabolism during aspirin overdose. Human & Experimental Toxicology. 1990;9(6):389–395. — PubMed PMID: 2271231
22. Needs CJ, Brooks PM. Clinical pharmacokinetics of the salicylates. Clinical Pharmacokinetics. 1985;10(2):164–177. — PubMed PMID: 3888490
23. Proudfoot AT, Krenzelok EP, Vale JA. Position paper on urine alkalinization. Journal of Toxicology: Clinical Toxicology. 2004;42(1):1–26. — PubMed PMID: 15083932
24. Belay ED, Bresee JS, Holman RC, Khan AS, Shahriari A, Schonberger LB. Reye's syndrome in the United States from 1981 through 1997. New England Journal of Medicine. 1999;340(18):1377–1382. — PubMed PMID: 10228187
25. Glasgow JF, Middleton B, Moore R, Gray A, Hill J. The mechanism of inhibition of beta-oxidation by aspirin metabolites in skin fibroblasts from Reye's syndrome patients and controls. Biochimica et Biophysica Acta. 1999;1454(1):115–125. — PubMed PMID: 10354521
26. Matsuo M, Terai K, Kameda N, Matsumoto A, Kurokawa Y, Funase Y, et al. Designation of enzyme activity of glycine-N-acyltransferase family genes and depression of glycine-N-acyltransferase in human hepatocellular carcinoma. Biochemical and Biophysical Research Communications. 2012;420(4):901–906. — PubMed PMID: 22475485
27. Badenhorst CP, Jooste M, van Dijk AA. Enzymatic characterization and elucidation of the catalytic mechanism of a recombinant bovine glycine N-acyltransferase. Drug Metabolism and Disposition. 2012;40(2):346–352. — PubMed PMID: 22071172
28. van der Sluis R, Badenhorst CP, van der Westhuizen FH, van Dijk AA. Characterisation of the influence of genetic variations on the enzyme activity of a recombinant human glycine N-acyltransferase. Gene. 2013;515(2):447–453. — PubMed PMID: 23237781
29. van der Sluis R, Ungerer V, Nortje C, van Dijk AA, Erasmus E. New insights into the catalytic mechanism of human glycine N-acyltransferase. Journal of Biochemical and Molecular Toxicology. 2017;31(11):e21963. — PubMed PMID: 28759163
30. Amsel LP, Levy G. Drug biotransformation interactions in man. II. A pharmacokinetic study of the simultaneous conjugation of benzoic and salicylic acids with glycine. Journal of Pharmaceutical Sciences. 1969;58(3):321–326. — PubMed PMID: 5782024
31. Yue TL, Varma DR. Pharmacokinetics, metabolism and disposition of salicylate in protein-deficient rats. Drug Metabolism and Disposition. 1982;10(2):147–152. — PubMed PMID: 6124400
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33. Sekhar RV, Patel SG, Guthikonda AP, Reid M, Balasubramanyam A, Taffet GE, et al. Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. American Journal of Clinical Nutrition. 2011;94(3):847–853. — PubMed PMID: 21795440
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