Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activities of glycerol 3-phosphate dehydrogenase (EC 1.1.1.8), glycerol kinase (EC 2.7.1.30), lactate dehydrogenase (EC 1.1.1.27), "malic' enzyme (L-malate-NADP+ oxidoreductase; EC 1.1.1.40) and the beta-oxoacyl-(acyl-carrier protein) reductase component of the fatty acid synthetase complex were measured in nine hepatoma lines (8 in rats, 1 in mouse) and in the livers of host animals. With the single exception of Morris hepatoma 16, which had unusually high glycerol 3-phosphate dehydrogenase activity, the activities of glycerol 3-phosphate dehydrogenase and glycerol kinase were highly correlated in normal livers and hepatomas (r = 0.97; P less than 0.01). The activities of these two enzymes were not strongly correlated with the activities of any of the other three enzymes. The primary function of hepatic glycerol 3-phosphate dehydrogenase appears to be in gluconeogenesis from glycerol.
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PMID:Proportional activities of glycerol kinase and glycerol 3-phosphate dehydrogenase in rat hepatomas. 17 86

Unlike the normal liver, numerous transplantable rodent and human hepatomas are unable to alter their rate of sterol synthesis and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-GoA) reductase [mevalonate: NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34] activity in response to a dietary cholesterol challenge. It has been suggested that this metabolic defect is linked to the process of malignant transformation. Hepatoma 7288C "lacks" feedback regulation of cholesterol synthesis when grown in vivo but expresses this regulatory property when grown in vitro (then called HTC). Therefore, it was used as a model system to answer whether an established hepatoma cell line that modulates its rate of cholesterol synthesis in vitro can express this property when grown in vivo, and whether cells reisolated from the tumor mass have the same regulatory phenotype as before transplantation. Our results show that long-term growth of hepatoma 7288C in tissue culture has not caused a biotransformation that permits feedback regulation of HMG-CoA reductase when the cells are transplanted back into host animals. In addition, HTC cells reisolated from the tumor mass and established in tissue culture continue to have the ability to regulate HMG-CoA reductase activity. Therefore, malignant transformation is not categorically linked to the loss of the cellular components necessary to regulate sterol synthesis and HMG-CoA reductase activity.
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PMID:Comparison of regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in hepatoma cells grown in vivo and in vitro. 18 7

The pre- and post-natal ontogeny of Sprague-Dawley rat liver aldehyde dehydrogenase [aldehyde-NAD(P)(+) oxidoreductase, EC 1.2.1.5] is described. At no time in its ontogenetic development does normal liver aldehyde dehydrogenase exhibit any of the characteristics of a series of unique aldehyde dehydrogenases that can be isolated from 2-acetamidofluorene-induced rat hepatomas. Enzyme activity is first detectable in 15-day foetal liver and gradually increases throughout pre- and post-natal development until adult activities are attained by day 49 after birth. Electrophoretically, normal aldehyde dehydrogenase, throughout its ontogeny, exists as the same single isoenzyme found in normal adult liver. Isoelectric points for two normal liver isoenzymes demonstrable by isoelectric focusing are pH5.9 and 6.0. The immunochemical properties of aldehyde dehydrogenase during its ontogeny are identical with those of normal adult liver aldehyde dehydrogenase when tested against anti-(hepatoma aldehyde dehydrogenase) serum in Ouchterlony double-diffusion tests. The results indicate that the hepatoma-specific aldehyde dehydrogenases are not the result of the de-repression of genes normally repressed in adult rat liver or in some other adult tissue.
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PMID:Aldehyde dehydrogenase in 2-acetamidofluorene-induced rat hepatomas. Ontogeny and evidence that the new isoenzymes are not due to normal gene de-repression. 19 78

Transplantable rat liver tumors 5123 t.c., 7288 ct.c., 5123 t.c.(H) and the Novikoff hepatoma have active mixed function oxidase systems capable of metabolizing a variety of drug and polycyclic hydrocarbon substrates. The tumor drug metabolism systems are at best 20% as active as rat liver. The tumor drug metabolism activities are induced by pretreatment with phenobarbital or beta-naphthoflavone and can be inhibited with specific inhibitors such as carbon monoxide or 7,8-benzoflavone. Tumor drug metabolism systems appear to consist of cytochrome P-450 and cytochrome P-450 reductase. The properties of the two protein components from tumors are highly similar to the corresponding components of the liver drug metabolism system. Cytochrome P-450 reductase has been at least partially purified from the Novikoff hepatoma and hepatoma 5123 t.c.(H). The kinetic and physical properties of the tumor reductases are similar to those of the liver reductase except that the Km of hepatoma 5123 t.c.(H) reductase, but not of the Novikoff hepatoma reductase for NADPH, is elevated an order of magnitude over the Km of the liver reductase. The mechanism for the interaction of electron donor and electron acceptor with liver or tumor reductases seems to be a sequential reaction mechanism. Experiments on the NADP-inhibition of the interaction of NADPH and cytochrome c with liver reductase indicate that NADP is competitive with NADPH and noncompetitive with cytochrome c. This result is consistent with the postulate of a sequential reaction for NADPH-cytochrome P-450 reductases of liver and tumors. These data support the conclusions that an active drug metabolism system is present in liver tumors and that the tumor systems are constituted like the liver system.
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PMID:The drug metabolism systems of liver and liver tumors: a comparison of activities and characteristics. 74 99

The mouse hepatoma cell line Hepa-1 was shown to express an aldehyde dehydrogenase (ALDH) isozyme which was inducible by TCDD and carcinogenic polycyclic aromatic hydrocarbons. The induced activity could be detected with benzaldehyde as substrate and NADP as cofactor (B/NADP ALDH). As compared with rat liver and hepatoma cell lines, the response was moderate (maximally 5-fold). There was an apparent correlation between this specific form of ALDH and aryl hydrocarbon hydroxylase (AHH) in the Hepa-1 wild-type cell line--in terms of inducibility by several chemicals. However, the magnitude of the response was clearly smaller for ALDH than for AHH. Southern blot analysis showed that a homologous gene (class 3 ALDH) was present in the rat and mouse genome. The gene was also expressed in Hepa-1 and there was a good correlation between the increase of class 3 ALDH-specific mRNA and B/NADP ALDH enzyme activity after exposure of the Hepa-1 cells to TCDD. It is concluded that class 3 ALDH is inducible by certain chemicals in the mouse hepatoma cell line, although the respective enzyme is not inducible in mouse liver in vivo.
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PMID:Induction of class 3 aldehyde dehydrogenase in the mouse hepatoma cell line Hepa-1 by various chemicals. 150 55

Kinetic studies of Morris 7777 hepatoma mitochondrial NAD(P) malic enzyme were consistent with an ordered mechanism where NAD adds to the enzyme before malate and dissociation of NADH from the enzyme is rate-limiting. In addition to its active site, malate apparently also associates with a lower affinity with an activator site. The activator fumarate competes with malate at the activator site and facilitates dissociation of NADH from the enzyme. The ratio of NAD(P) malic enzyme to malate dehydrogenase activity in the hepatoma mitochondrial extract was found to be too low, even in the presence of known inhibitors of malate dehydrogenase, to account for the known ability of NAD(P) malic enzyme to intercept exogenous malate from malate dehydrogenase in intact tumor mitochondria (Moreadith, R.W., and Lehninger, A.L. (1984) J. Biol. Chem. 259, 6215-6221). However, NAD(P) malic enzyme may be able to intercept exogenous malate because according to the present results, it can associate with the pyruvate dehydrogenase complex, which could localize NAD(P) malic enzyme in the vicinity of the inner mitochondrial membrane. The activity levels of some key metabolic enzymes were found to be different in Morris 7777 mitochondria than in liver or mitochondria of other rapidly dividing tumors. These results are discussed in terms of differences among tumors in their ability to utilize malate, glutamate, and citrate as respiratory fuels.
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PMID:Kinetics and regulation of hepatoma mitochondrial NAD(P) malic enzyme. 158 26

The NAD- and NADP-dependent aldehyde dehydrogenase (ALDH) activities were evaluated in two rat hepatoma cell lines, namely the well-differentiated MH1C1 line and the less differentiated HTC line. Each activity was determined in parallel in isolated rat hepatocytes, for comparison. The aliphatic aldehyde acetaldehyde (ACA) and the aromatic aldehyde benzaldehyde (BA) were used as substrates. With the first substrate the ALDH activities found in the crude cytoplasmic extracts were lower in hepatoma cells than in normal hepatocytes, especially when measured with NADP as coenzyme (ACA/NADP). Otherwise, with benzaldehyde as substrate the NAD-dependent enzyme activity (BA/NAD) was increased about 9-fold in HTC cells over hepatocytes and decreased in MH1C1 cells, while the NADP-dependent (BA/NADP) activity was increased 38- and 2.5-fold in HTC and MH1C1 cell lines, respectively. Studies on the subcellular distribution of these enzyme activities showed that the activity measured with acetaldehyde and NAD (ACA/NAD) was almost equally distributed between the cytosol and the subcellular particles in the three cell populations, but the ACA/NADP activity was shifted towards the cytosolic compartment in hepatomas, especially in HTC cells. The BA/NAD and BA/NADP ALDH activities found in the organelles of hepatoma cells were markedly reduced in comparison with hepatocytes, in favour of the cytosol. The most striking difference between the normal and the transformed cells was the 94-fold increase over hepatocytes of the BA/NADP activity, found in the cytosolic fractions of HTC cells. MH1C1 cells showed a less pronounced (7.5-fold) enhancement of this tumour-associated specific activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative subcellular distribution of benzaldehyde and acetaldehyde dehydrogenase activities in two hepatoma cell lines and in normal hepatocytes. 166 Dec 6

We have isolated and characterized cDNA clones encoding rat liver cytosol 10-formyltetrahydrofolate dehydrogenase (EC 1.5.1.6). An open reading frame of 2706 base pairs encodes for 902 amino acids of Mr 99,015. The deduced amino acid sequence contains exact matches to the NH2-terminal sequence (28 residues) and the sequences of five peptides derived from cyanogen bromide cleavage of the purified protein. The amino acid sequence of 10-formyltetrahydrofolate dehydrogenase has three putative domains. The NH2-terminal sequence (residues 1-203) is 24-30% identical to phosphoribosylglycinamide formyltransferase (EC 2.1.2.2) from Bacillus subtilis (30%), Escherichia coli (24%), Drosophila melanogaster (24%), and human hepatoma HepG2 (27%). Residues 204-416 show no extensive homology to any known protein sequence. Sequence 417-900 is 46% (mean) identical to the sequences of a series of aldehyde dehydrogenase (NADP+) (EC 1.2.1.3). Intact 10-formyltetrahydrofolate dehydrogenase exhibits NADP-dependent aldehyde dehydrogenase activity. The sequence identity to phosphoribosylglycinamide formyltransferase is discussed, and a binding region for 10-formyltetrahydrofolate is proposed.
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PMID:Isolation and characterization of cDNA clones for rat liver 10-formyltetrahydrofolate dehydrogenase. 184 31

Parallel investigations of the transamination pathways of glutamine oxidation in Ehrlich ascites carcinoma (EAC) and AS 30D hepatoma revealed that hepatoma cells, unlike EAC, produce very little aspartate. This cannot be explained by differences in the activity of glutamine-metabolizing enzymes. Also, the mitochondria from the hepatoma respired at a similar rate to EAC mitochondria with glutamine as sole substrate producing substantial amounts of aspartate. Unlike their isolated mitochondria, intact hepatoma cells showed a very low rate of glutamine oxidation. Compared with EAC, the rate of L-[U-14C]glutamine consumption by AS 30D hepatoma cells was much lower, with insignificant production of 14C-labelled aspartate and CO2. This suggested that the glutamine-transporting system in the hepatoma cell plasma membrane had a very low activity. Isolated hepatoma mitochondria produced 3 times more pyruvate from malate than did EAC mitochondria, indicating a higher activity of NAD(P)-dependent malic enzyme. We postulate that an active malic enzyme may suppress the synthesis of aspartate in hepatoma cells, but further evidence is needed to confirm this assumption.
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PMID:Control and function of the transamination pathways of glutamine oxidation in tumour cells. 199 Oct 25

The properties of glucose-6-phosphate dehydrogenase (G6PDH; glucose-6-phosphate-NADP-oxidoreductase, EC 1.1.1.49) in the liver tissue of intact rats and those with ascites Zaidel hepatoma were compared. The specific activity of the enzyme from hepatoma was 7 times as high as that of the enzyme from the normal liver. The G6PDH preparations with the specific activity of 1.5 U/mg of protein were obtained by the three-stage purification. No differences in kinetic properties, coenzyme specificity and electrophoretic mobility of the enzymes from hepatoma and normal liver were observed.
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PMID:[Properties of glucose-6-phosphate dehydrogenase of the liver tissue of intact rats and rats with Zaidel ascitic hepatoma]. 234 30


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