ELIZA

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731925 occurrences (No.6 in the rank) during 5 years in the PubMed. [cache]

454) Although AOX expression has been confirmed in several extrahepatic tissues, activities therein and potential contribution to overall human clearance have not been thoroughly studied.

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PMID:34162687 DOI:10.1124/dmd.120.000313

2021 Drug metabolism and disposition: the biological fate of chemicals

* Contribution of Extrahepatic Aldehyde Oxidase Activity to Human Clearance.

- Aldehyde oxidase (AOX) is a soluble, cytosolic enzyme that metabolizes various N-heterocyclic compounds and organic aldehydes. It has wide tissue distribution with highest levels found in liver, kidney, and lung. Human clearance projections of AOX substrates by in vitro assessments in isolated liver fractions (cytosol, S9) and even hepatocytes have been largely underpredictive of clinical outcomes. Various hypotheses have been suggested as to why this is the case. One explanation is that extrahepatic AOX expression contributes measurably to AOX clearance and is at least partially responsible for the often observed underpredictions. Although AOX expression has been confirmed in several extrahepatic tissues, activities therein and potential contribution to overall human clearance have not been thoroughly studied. In this work, the AOX enzyme activity using the S9 fractions of select extrahepatic human tissues (kidney, lung, vasculature, and intestine) were measured using carbazeran as a probe substrate. Measured activities were scaled to a whole-body clearance using best-available parameters and compared with liver S9 fractions. Here, the combined scaled AOX clearance obtained from the kidney, lung, vasculature, and intestine is very low and amounted to <1% of liver. This work suggests that AOX metabolism from extrahepatic sources plays little role in the underprediction of activity in human. One of the notable outcomes of this work has been the first direct demonstration of AOX activity in human vasculature. SIGNIFICANCE STATEMENT: This work demonstrates aldehyde oxidase (AOX) activity is measurable in a variety of extrahepatic human tissues, including vasculature, yet activities and potential contributions to human clearance are relatively low and insignificant when compared with the liver. Additionally, the modeling of the tissue-specific in vitro kinetic data suggests that AOX may be influenced by the tissue it resides in and thus show different affinity, activity, and modified activity over time.

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(1)186 of	(8)11 by	(15)4 as	(22)2 enable
(2)36 in	(9)10 Quantitative	(16)3 increased	(23)2 for
(3)34 and	(10)7 data	(17)3 level	(24)2 or
(4)30 null	(11)6 is	(18)3 signatures	(25)2 patterns,
(5)15 levels	(12)6 quantitative	(19)3 system	(26)2 were
(6)14 was	(13)5 patterns	(20)2 across	(27)2 which
(7)13 analysis	(14)5 profiles	(21)2 can

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--- WordNet output for expression --- =>表現すること, 式, 表現, 表示, 言い回し, 表現法, 表情 Overview of noun expression The noun expression has 9 senses (first 6 from tagged texts) 1. (23) expression, look, aspect, facial expression, face -- (the feelings expressed on a person's face; "a sad expression"; "a look of triumph"; "an angry face") 2. (18) expression, manifestation, reflection, reflexion -- (expression without words; "tears are an expression of grief"; "the pulse is a reflection of the heart's condition") 3. (15) expression, verbal expression, verbalism -- (the communication (in speech or writing) of your beliefs or opinions; "expressions of good will"; "he helped me find verbal expression for my ideas"; "the idea was immediate but the verbalism took hours") 4. (5) saying, expression, locution -- (a word or phrase that particular people use in particular situations; "pardon the expression") 5. (4) formulation, expression -- (the style of expressing yourself; "he suggested a better formulation"; "his manner of expression showed how much he cared") 6. (4) formula, expression -- (a group of symbols that make a mathematical statement) 7. expression -- ((genetics) the process of expressing a gene) 8. construction, grammatical construction, expression -- (a group of words that form a constituent of a sentence and are considered as a single unit; "I concluded from his awkward constructions that he was a foreigner") 9. expression -- (the act of forcing something out by squeezing or pressing; "the expression of milk from her breast") --- WordNet end ---