Acrylamide biotransformation and exposure biomarkers (WP4233)

Homo sapiens

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Acrylamide (AA) is absorbed from the gastrointestinal tract and is converted to toxic glycidamide (GA) by cytochrome P450 2E1. Both AA and GA are coupled with glutathione (GSH) in the liver to form conjugates that are metabolized in the kidney and urinary tract to form modified merbapturic acids (AAMA and GAMA) that serve as biomarkers for AA in urine. Meanwhile, haemoglobin adducts are formed in the blood, including AA-Valine and GA-Valine. Genotoxic and carcinogenic activity is mediated by GA and the formation of DNA adducts with guanine and adenosine.

Authors

Alex Pico , Egon Willighagen , and Eric Weitz

Activity

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Organisms

Homo sapiens

Communities

Annotations

Cell Type Ontology

kidney cell hepatocyte

Pathway Ontology

classic metabolic pathway glutathione conjugates processing - the mercapturic acid pathway phase I biotransformation pathway via cytochrome P450

Participants
Query Drugst.One

Label Type Compact URI Comment
Acrylamide (AA) Metabolite chebi:28619
AAMA Metabolite chemspider:138886
Glutathione Metabolite chebi:16856
AA-Val Metabolite chemspider:29332409
Valine Metabolite chebi:16414
Glycidamide (GA) Metabolite pubchem.compound:91550
GAMA Metabolite chemspider:57262168
GA-Val Metabolite chemspider:28573496
CYP2E1 GeneProduct ncbigene:1571

References

  1. Exposure assessment of process-related contaminants in food by biomarker monitoring. Rietjens IMCM, Dussort P, Günther H, Hanlon P, Honda H, Mally A, et al. Arch Toxicol. 2018 Jan;92(1):15–40. PubMed Europe PMC Scholia