Disease relevance of ALLYLISOPROPYLACETAMIDE

• Inhibition of the acute toxicity and adrenocorticolytic effect of 7,12-dimethylbenz(a)anthracene by isopropylvaleramide and allylisopropylacetamide in the rat [1].
• The induction of ALA synthase in chronic iron overload was enhanced by phenobarbital and allylisopropylacetamide, in spite of the fact that these agents did not increase haem oxygenase activity [2].
• In rhesus monkeys, in which porphyria was induced by the administration of allylisopropylacetamide (AIA), hepatic delta-aminolevulinic acid synthase (ALA-S) was increased [3].
• Heme administration causes inhibition of delta-aminolevulinate synthase (ALAS), best tested in the allylisopropylacetamide (AIA)-treated rat, a model for hepatic porphyrias [4].
• Intraperitoneal injection of 2 mmol/kg serine 24 hr after AIA administration was used as an animal model for an acute psychosis, by measuring catalepsy scores 30 min after serine injection [5].

High impact information on ALLYLISOPROPYLACETAMIDE

• In this study, cobalt was shown to block almost entirely the ability of the barbiturate analogue allylisopropylacetamide to induce delta-aminolevulinate synthase in liver [6].
• When the metal was administered 1.5 or more hours after allylisopropylacetamide, inhibition of enzyme induction was incomplete [6].
• Allylisopropylacetamide (AIA) and isopropylvaleramide (IVA) have been demonstrated previously to protect in vivo against the acute toxicity and adrenal necrotic effect of 7,12-dimethylbenz(a)anthracene [7].
• Kinetic evidence for heterogeneous responsiveness of mixed function oxidase isozymes to inhibition and induction by allylisopropylacetamide in chick embryo liver [8].
• Changes in hepatic mixed function oxidase kinetics after administration of allylisopropylacetamide (AIA) to chick embryos indicate that the activities of different cytochrome P-450 isozymes, including those participating in the metabolism of the same substrates, can be simultaneously increased and inhibited by a single xenobiotic [8].

Biological context of ALLYLISOPROPYLACETAMIDE

• The 201 product molecules of cytochrome P-450-mediated turnover of allylisopropylacetamide in either the microsomal or purified enzyme system are probably the epoxide, are reactive toward alkylation of cellular nucleophiles, and covalently modify protein and exogenous calf thymus DNA molecules [9].
• Allylisopropylacetamide markedly lowered lipid peroxidation caused by CCl4 in proportion to the loss of cytochrome P450 [10].
• However, the possibility remained that a minute portion of the inactivating AIA-species escaped the catalytic site of the generating hemoprotein and alkylated the nonprosthetically bound isotopic heme [11].
• The role of catalase in lipid metabolism has been studied by means of a comparison of the turnover characteristics of the major lipid classes in the normal mouse with those of animals in which the catalase activity had been inhibited and blocked by aminotriazole and allylisopropylacetamide [12].
• The influence of pretreatment with allylisopropylacetamide (AIA) and phenobarbital (PB) on the pharmacokinetics and metabolite profile of antipyrine was studied in rats in vivo [13].

Anatomical context of ALLYLISOPROPYLACETAMIDE

• Inorganic cobalt was found to induce heme oxygenase activity in primary cultures of embryonic chick liver cells and to inhibit the induction of delta-aminolevulinate synthetase by the porphyrinogenic compounds allylisopropylacetamide, dicarbethoxy-1,4-dihydrocollidine, etiocholanolone, phenobarbital, Aroclor (R)1254, and secobarbital [14].
• After the heme moiety of hepatic cytochrome P-450 in rats had been destroyed by allylisopropylacetamide (AIA), intravenously injected heme significantly increased the cytochrome P-450 content and mixed function oxidase activity of liver microsomes [15].
• On the other hand, IVA and AIA did not affect cytotoxicity, the frequencies of SCE induced by CPP or B[a]P, nor BPDE-induced mutations in CHO cells [16].
• The levels of ALAS which accumulated in the cytosol after allylisopropylacetamide administration were proportionally greater in both the young and senescent than in the mature animals [17].
• Finally, the distributions of ALA synthase mRNA were compared in polysomes isolated from hepatocytes which had been incubated with AIA for 5 h in the presence and absence of 10 microM hemin in the medium [18].

Associations of ALLYLISOPROPYLACETAMIDE with other chemical compounds

• In phenobarbital-induced rat liver microsomes about 70% of the cytochrome P-450-mediated N,N-dimethylaniline N-demethylase activity is sensitive to allylisopropylacetamide inactivation; the residual 30% of the N-demethylase activity is incapable of allylisopropylacetamide turnover and insensitive to allylisopropylacetamide inactivation [9].
• Hydrocortisone is known to restore the impaired inducibility of delta-aminolevulinate synthase by allylisopropylacetamide in adrenalectomized rats [19].
• Studies of the porphyrin-inducing activity of ethynyl compounds and conformationally restricted and unrestricted analogues of allylisopropylacetamide in chick embryo liver cell culture [20].
• We have determined in this study, using immune-blot analyses, that administration in ovo of allylisopropylacetamide (AIA) in combination with diethyl 1,4-dihydro-2,4,6-trimethyl,3,5-pyridinedicarboxylate (DDC) increased the mass of ALA synthase in intestine and kidney of chick embryos [21].
• In addition, allylisopropylacetamide caused a slight drop in intracellular cAMP while testosterone caused the levels of cAMP to rise to 260% of the basal levels measured in hepatocytes in culture [22].

Gene context of ALLYLISOPROPYLACETAMIDE

• We measured the half-life of the hepatic delta-aminolevulinate synthase mRNA by RNA blot hybridization analysis using allylisopropylacetamide-induced porphyric rats as an experimental model and the rat cDNA as a hybridization probe [23].
• The results with TTMS and AIA, but not with 4-ethyl DDC, were the same in individual human enzymes expressed in Supersomes and human liver microsomes [24].
• On the 2nd day in cluture, the level of amino-levulinate (ALA) synthase activity in response to allylisopropylacetamide (AIA) was increased 6-fold in cells grown in F12 [25].
• Effect of allylisopropylacetamide on Nuclear Ribonucleic Acid synthesis in rat liver [26].
• Evidence for altered hepatic catalase molecules in allylisopropylacetamide-treated mice [27].

Analytical, diagnostic and therapeutic context of ALLYLISOPROPYLACETAMIDE

• Intraperitoneal injection of allylisopropylacetamide (350 mumol) induced activity of the enzyme fourfold [28].
• Quantitative rocket immunoelectrophoresis showed that the protein moiety of the major phenobarbital-inducible form of hepatic cytochrome P-450 was not diminished up to 1 h, but was markedly decreased (to 43% of that of the phenobarbital-treated control) at 20 h after allylisopropylacetamide treatment [29].
• The decrease in activity of 5-aminolaevulinate synthase produced by administration of CoCl2 was greater after treatment with 2-allyl-2-isopropylacetamide than after treatment with allylisopropylacetamide and 3,4,3',4'-tetrachlorobiphenyl [30].
• In the group living under low atmospheric pressure (51 kPa) the enzymic activity, either basal or induced by starvation and/or allylisopropylacetamide, was significantly (p less than 0.001) lower than that of the control group [31].

References