Biomaterial Database

Acetaminophen metabolism by cytochrome P450 monooxygenases in Parkinson's disease. 1989

S A Factor, and W J Weiner, and F Hefti

Department of Neurology, Albany Medical College, NY.

It has been suggested that alterations in the activity of cytochrome P450 monooxygenases may play a role in the pathogenesis of Parkinson's disease, particularly in patients who had onset before the age of 40. We studied the P450-mediated metabolism of acetaminophen to 3-hydroxy-acetaminophen in 26 patients with Parkinson's disease and in 18 control subjects. After subjects ingested 1,000 mg acetaminophen, urine was collected under controlled conditions. Acetaminophen and 3-hydroxy-acetaminophen were measured in the urine using newly developed high-pressure liquid chromatography methods. The ratio of 3-hydroxy-acetaminophen to acetaminophen was calculated for each patient and no significant differences were observed in patients compared with control subjects. Abnormal metabolism was not observed in patients who had onset of Parkinson's disease at or before the age of 40. In addition, no difference in metabolic activity was observed between the patients who were treated with levodopa/carbidopa and those who were not treated. These findings suggest that there are no alterations of P450-mediated metabolism of acetaminophen in patients with Parkinson's disease.

UI	MeSH Term	Description	Entries
D007980	Levodopa	The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.	L-Dopa,3-Hydroxy-L-tyrosine,Dopaflex,Dopar,L-3,4-Dihydroxyphenylalanine,Larodopa,Levopa,3 Hydroxy L tyrosine,L 3,4 Dihydroxyphenylalanine,L Dopa
D008297	Male		Males
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D010300	Parkinson Disease	A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)	Idiopathic Parkinson Disease,Lewy Body Parkinson Disease,Paralysis Agitans,Primary Parkinsonism,Idiopathic Parkinson's Disease,Lewy Body Parkinson's Disease,Parkinson Disease, Idiopathic,Parkinson's Disease,Parkinson's Disease, Idiopathic,Parkinson's Disease, Lewy Body,Parkinsonism, Primary
D002230	Carbidopa	An inhibitor of DOPA DECARBOXYLASE that prevents conversion of LEVODOPA to dopamine. It is used in PARKINSON DISEASE to reduce peripheral adverse effects of LEVODOPA. It has no anti-parkinson activity by itself.	Methyldopahydrazine,Carbidopa, (R)-Isomer,Carbidopa, (S)-Isomer,Lodosin,Lodosyn,MK-485,MK-486,MK 485,MK 486,MK485,MK486
D003577	Cytochrome P-450 Enzyme System	A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.	Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000082	Acetaminophen	Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.	Acetamidophenol,Hydroxyacetanilide,Paracetamol,APAP,Acamol,Acephen,Acetaco,Acetominophen,Algotropyl,Anacin-3,Datril,N-(4-Hydroxyphenyl)acetanilide,N-Acetyl-p-aminophenol,Panadol,Tylenol,p-Acetamidophenol,p-Hydroxyacetanilide,Anacin 3,Anacin3