Disease relevance of Porphyrias, Hepatic

• Variegate porphyria (VP) is an acute hepatic porphyria with autosomal dominant inheritance due to a partial deficiency of protoporphyrinogen oxidase (PPOX) activity [1].
• Hereditary coproporphyria (HC) is an acute hepatic porphyria with autosomal dominant inheritance caused by deficient activity of coproporphyrinogen III oxidase (COX) [2].
• Tryptophan pyrrolase, the regulatory free haem and hepatic porphyrias. Early depletion of haem by clinical and experimental exacerbators of porphyria [3].
• Acute intermittent porphyria (AIP), the most common hepatic porphyria, results from the half-normal activity of hydroxymethylbilane synthase (HMB-synthase; EC 4.3.1.8), the third enzyme in the heme biosynthetic pathway [4].
• These observations may be relevant to the biochemical mechanisms involved in the ethanol-related conditions, sideroblastic anaemia, cutaneous hepatic porphyria and hepatic siderosis [5].

Psychiatry related information on Porphyrias, Hepatic

• The results show that tryptophan metabolism and disposition can be influenced by changes in liver haem concentration, and are discussed briefly in relation to mood disorders in the hepatic porphyrias [6].

High impact information on Porphyrias, Hepatic

• Porphobilinogen deaminase deficiency in mice causes a neuropathy resembling that of human hepatic porphyria [7].
• L-tryptophan: a common denominator of biochemical and neurological events of acute hepatic porphyria [8]?
• These findings in a rat model of hepatic porphyria suggest that Sn-protoporphyrin may be useful in the treatment of acute exacerbations of "inducible" hepatic porphyrias in man, especially since Sn-protoporphyrin, unlike hematin which is presently used for this purpose, is neither degraded by nor induces the activity of heme oxygenase [9].
• Abnormalities in liver function and morphology and impaired aminopyrine metabolism in hereditary hepatic porphyrias [10].
• Hereditary coproporphyria (HCP), an autosomal dominant acute hepatic porphyria, results from mutations in the gene that encodes coproporphyrinogen III oxidase (CPO) [11].

Chemical compound and disease context of Porphyrias, Hepatic

• PK 11195 aggravates 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced hepatic porphyria in rats [12].
• We examined the biochemical and ultrastructural alterations in rat liver following experimentally induced acute hepatic porphyria, as well as the effects of the administration of a selective PBR ligand, PK 11195 [12].
• These data may be relevant for the treatment with glucose and heme of patients with "inducible" hepatic porphyria [13].
• Among the actions of 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) in mice is the induction of hepatic porphyria [14].
• Seizure management in acute hepatic porphyria: risks of valproate and clonazepam [15].

Biological context of Porphyrias, Hepatic

• Protein binding of salicylate in cutaneous hepatic porphyria [16].
• The association between an in vivo oxidative stress condition of the liver and hepatic porphyria during HCB intoxication is postulated [17].
• The results indicated that occupational exposure to hexachlorobenzene and octachlorostyrene in aluminum degassing with hexachloroethane may affect porphyrin metabolism in a manner consistent with early secondary coproporphyrinuria-the first recognized step in the development of chronic hepatic porphyria [18].
• Variegate porphyria (VP), one of the acute hepatic porphyrias, is characterized by a partial reduction in the activity of protoporphyrinogen oxidase (PPO), and recently, mutations in the PPO gene on chromosome 1q22-23 have been described [19].

Anatomical context of Porphyrias, Hepatic

• Of the patients, 84% showed a significant decrease of erythrocyte uroporphyrinogen-decarboxylase (UD; EC 4.1.1.37) activity to approximately 50% of control levels suggesting a hereditary predisposition for the development of a chronic hepatic porphyria [20].

Gene context of Porphyrias, Hepatic

• Hereditary coproporphyria (HC) is an acute hepatic porphyria with autosomal dominant inheritance caused by a deficient activity of coproporphyrinogen IX oxidase (CPX) [21].
• A new form of acute hepatic porphyria with double genetic defect--deficiency of porphobilinogen deaminase and coproporphyrinogen oxidase--is described [22].
• Hexachlorobenzene (HCB) produces hepatic porphyria and induces the hepatic cytochrome P450 isozymes P450c (P450IA1) and P450d (P450IA2) in rodents [23].
• A defect in the activity of uroporphyrinogen decarboxylase may exist in cutaneous hepatic porphyria but this could not be demonstrated in erythrocytes in this study [24].
• Acute hepatic porphyria syndrome with porphobilinogen synthase defect [25].

Analytical, diagnostic and therapeutic context of Porphyrias, Hepatic

• The aminopyrine breath test and measurement of postprandial serum bile acids were performed in 67 patients with well-documented hereditary hepatic porphyria [10].
• (1) Plasma protein binding of salicylate was studied in 14 patients with cutaneous hepatic porphyria (CHP) and 11 normal subjects using ultrafiltration with centrifugation (membrane cones) and continuous ultrafiltrations [16].

References