Browsing Pathways

Para-cresol(P-cresol) is a phenolic compound that is formed through gut microbial metabolism from the amino acid tyrosine which is acquired from foods that are high in protein. After being transported into gut microbes, tyrosine undergoes reactions with the enzymes tyrosine transaminase, 4-hydroxyphenylpyruvate oxidase and 4-hydroxylphenylacetate decarboxylase to form para-cresol. Most of the p-cresol that is produced from the gut microbes then enters systemic circulation. P-cresol can then undergo sulfation or glucuronidation reactions in the liver to produce the uremic toxins p-cresyl sulfate and p-cresyl glucuronide respectively. However, P-cresol itself can also be a uremic toxin with widespread toxic effects on the body. P-cresol is shown to be associated with cardiovascular disease and it can also inhibit endothelial cell proliferation.

85-90% of an oral dose undergoes first pass metabolism by carboxylesterase 1 in the liver to an inactive carboxylic acid metabolite. About 2% of clopidogrel is oxidized to 2-oxoclopidogrel. This conversion is 35.8% by CYP1A2, 19.4% by CYP2B6, and 44.9% by CYP2C194 though other studies suggest CYP3A4, CYP3A5, and CYP2C9 also contribute. 2-oxoclopidogrel is further metabolized to the active metabolite. This conversion is 32.9% by CYP2B6, 6.79% by CYP2C9, 20.6% by CYP2C19, and 39.8% by CYP3A4.

Eplerenone is metabolized primarily by CYP3A4, however, no active metabolites have been identified in human plasma. Eplerenone binds to the mineralocorticoid receptor and thereby blocks the binding of aldosterone (component of the renin-angiotensin-aldosterone-system, or RAAS). Aldosterone synthesis, which occurs primarily in the adrenal gland, is modulated by multiple factors, including angiotensin II and non-RAAS mediators such as adrenocorticotropic hormone (ACTH) and potassium. Aldosterone binds to mineralocorticoid receptors in both epithelial (e.g., kidney) and nonepithelial (e.g., heart, blood vessels, and brain) tissues and increases blood pressure through induction of sodium reabsorption and possibly other mechanisms. (DrugBank)

Abscisic acid biosynthesis is a pathway that begins in the chloroplast and ends in the cytosol by which violaxanthin becomes abscisic acid, a plant hormone that plays a role in many plant developmental processes, including bud dormancy . First, neoxanthin synthase catalyzes the opening of the violaxanthin epoxide ring to form neoxanthin. Second, a yet unidentified neoxanthin isomerase is theorized to isomerize neoxanthin to 9'-cis-neoxanthin. Third, 9-cis-epoxycarotenoid dioxygenase (NCED) uses oxygen to cleave 9'-cis-neoxanthin to form xanthoxin and C25-allenic-apo-aldehyde. This enzyme requires Fe2+ as a cofactor. Next, a xanthoxin transporter is theorized to export xanthoxin from the chloroplast into the cytosol to continue abscisic acid biosynthesis, but it has yet to be discovered. Fourth, xanthoxin dehydrogenase, located in the cytosol, catalyzes the conversion of xanthoxin and NAD to abscisic aldehyde, NADH, and a proton with the help of a molybdenum cofactor (MoCo). Fifth, abscisic-aldehyde oxidase converts abscisic aldehyde, water, and oxygen into hydrogen peroxide, hydrogen ion, and abscisic acid.