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)

Activities and isoenzyme patterns of gamma-glutamyl transferase (GGT) were studied in serum samples from fifteen Bantu males suffering from primary hepatoma; the results were compared with those obtained from normal samples. Enzyme activities were significantly higher in hepatoma patients than in controls. Results with Cellogel electrophoresis and the fluorescent substrate gamma-L-glutamine-7-amido-4-methylcoumarin were reproducible; two major bands of activity were observed in normal serum and three bands in hepatoma serum. The additional band seen in hepatoma serum was also detected in serum from patients with certain other disorders. With polyacrylamide gel electrophoresis using either gamma-L-glutamyl-alpha-naphthylamide or gamma-L-glutamyl-p-nitroanilide as substrates, results were inconsistent and difficult to interpret since there was a lack of specificity for GGT.
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PMID:Electrophoretic studies of serum gamma-glutamyl transferase from patients with hepatoma. 286 14

Well coupled mitochondria were isolated from transplantable chicken hepatoma induced by MC-29 virus. The mitochondrial phosphate-dependent and phosphate-independent glutaminase activities were increased compared with those from normal chicken liver. Glutamate dehydrogenase was undetectable in the tumor mitochondria. Oxypolarographic tests showed the following: glutamine oxidation was prominent in the tumor mitochondria and was mediated through an NAD-linked reaction, while mitochondria from the liver showed a feeble glutamine oxidation; glutamine oxidation by tumor mitochondria was inhibited either by aminooxyacetate, inhibitor of transaminases, or prior incubation of mitochondria with DON (6-diazo-5-oxonorleucine), which inhibited mitochondrial glutaminases. Bromofuroate, inhibitor of glutamate dehydrogenase, had little or no effect; and glutamate oxidation was also inhibited by aminooxyacetate, while it was not affected by DON. These findings clearly show a high glutamate oxidation activity in the hepatoma and indicate that the product of glutamine hydrolysis, glutamate, is catabolized via transamination in the mitochondria to supply ATP.
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PMID:Prominent glutamine oxidation activity in mitochondria of avian transplantable hepatoma induced by MC-29 virus. 301 1

Human AP-2 is a sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to stimulate transcription of selected genes. Here, we report the isolation and characterization of a human cDNA clone containing the entire protein-coding region of AP-2. The deduced primary amino acid sequence of AP-2 does not contain a domain resembling any previously identified DNA binding motif. However, an interesting feature of the AP-2 protein is a clustered arrangement of proline and glutamine residues that have been found recently within the activation domains of other transcription factors. Expression of the AP-2 clone in bacteria yields a protein that binds to DNA and activates transcription in vitro in a comparable manner to native human AP-2. Transfection of cDNA clones into Drosophila cells indicates that the AP-2 gene product can also activate gene expression in vivo in a DNA template-dependent manner. Expression of endogenous AP-2 is repressed in a hepatoma cell line and stimulated following retinoic-acid-induced differentiation of a human teratocarcinoma cell line. This indicates that AP-2 may be a transcription factor involved in the control of developmentally regulated gene expression.
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PMID:Cloning and expression of AP-2, a cell-type-specific transcription factor that activates inducible enhancer elements. 306 3

The transport of L-threonine and L-glutamine into murine P388 leukemia cells has been characterized. Threonine appears to be a specific substrate for a Na+-dependent amino acid transport system similar to system ASC of the HTC hepatoma cell. Threonine transport is uninhibited by 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid and alpha-(methylamino)isobutyric acid, shows a pattern of transport similar to that seen in HTC hepatoma cells over the pH range of 5.5-7.5, and is inhibited by L-serine and L-cysteine. Approximately two-thirds of glutamine transport into P388 cells also appears to enter P388 cells via this ASC-analogous system. However, based upon (a) inhibition studies with threonine (where the K1 of threonine inhibition of glutamine transport was 7-fold the Km of threonine transport), (b) inhibition analysis of glutamine transport with various amino acids and amino acid analogues, and (c) different patterns of transport between threonine and glutamine over the pH range of 5.5-7.5, approximately one-third of glutamine transport can be attributed to a second Na+-dependent amino acid transport system. This system appears to be similar to the system N of rat hepatocytes. Glutamine and threonine do not appear to enter P388 cells via systems A or L to any significant degree. P388 cells do not appear to exhibit 'adaptive regulation' of amino acid transport. Differences in 'adaptive regulation' could therefore not be utilized for comparing threonine and glutamine transport.
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PMID:Characterization of L-threonine and L-glutamine transport in murine P388 leukemia cells in vitro. Presence of an N-like amino acid transport system. 308 65

The CO2-ratios method is applied to the analysis of abnormalities of TCA (tricarboxylic acid)-cycle metabolism in AS-30D rat ascites-hepatoma cells. This method utilizes steady-state 14CO2-production rates from pairs of tracers of the same compound to evaluate TCA-cycle flux patterns. Equations are presented that quantitatively convert CO2 ratios into estimates of probability of flux through TCA-cycle-related pathways. Results of this study indicated that the ratio of 14CO2 produced from [1,4-14C]succinate to 14CO2 produced from [2,3-14C]succinate was increased by the addition of glutamine (5 mM) to the medium. An increase in the succinate CO2 ratio is quantitatively related to an increased flux of unlabelled carbon into the TCA-cycle-intermediate pools. Analysis of 14C distribution in [14C]citrate derived from [2,3-14C]succinate indicated that flux from the TCA cycle to the acetyl-CoA-derived carbons of citrate was insignificant. Thus the increased succinate CO2 ratio observed in the presence of glutamine could only result from an increased flux of carbon into the span of the TCA cycle from citrate to oxaloacetate. This result is consistent with increased flux of glutamine to alpha-oxoglutarate in the incubation medium containing exogenous glutamine. Comparison of the pyruvate CO2 ratio, steady-state 14CO2 production from [2-14C]pyruvate versus [3-14C]pyruvate, with the succinate 14CO2 ratio detected flux of pyruvate to C4 TCA-cycle intermediates in the medium containing glutamine. This result was consistent with the observation that [14C]aspartate derived from [2-14C]pyruvate was labelled in C-2 and C-3. 14C analysis also produced evidence for flux of TCA-cycle carbon to alanine. This study demonstrates that the CO2-ratios method is applicable in the analysis of the metabolic properties of AS-30D cells. This methodology has verified that the atypical TCA-cycle metabolism previously described for AS-30D-cell mitochondria occurs in intact AS-30D rat hepatoma cells.
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PMID:Analysis of tricarboxylic acid-cycle metabolism of hepatoma cells by comparison of 14CO2 ratios. 312 Jun 98

Succinylacetone (SA) (4,6-dioxoheptanoic acid) is an abnormal metabolite produced in patients with hereditary tyrosinemia as a consequence of an inherited deficiency of fumaryl acetoacetate hydrolase activity. Patients with this disease are associated with a number of abnormalities, including aminoaciduria, proteinuria, liver failure, commonly hepatoma, and decreased GSH concentration in the liver. In the course of our studies of tyrosinemia, we found that the urine of patients with this disorder contains material(s) that absorbs light at 315 nm. We investigated the nature of the 315 nm material in detail. SA was found to react with amino acids and protein nonenzymatically, to form stable adducts at physiological temperature and pH. All SA adducts with amino acids and/or proteins exhibited an absorption peak at 315 nm. Although all amino acids reacted with SA, the most reactive amino acid was lysine (Lys), followed, in order, by glycine, methionine, phenylalanine, serine, alanine, and glutamine. SA-adducts were unstable at pH below 6, while they were made considerably more stable after reduction with NaBH4, suggesting that SA forms an adduct via Schiff base formation. High-performance liquid chromatography (HPLC) analysis of urines from patients with tyrosinemia revealed the existence of SA-glycine, SA-methionine, SA-tyrosine, and SA-phenylalanine. After digestion of urines with proteinase K, three more HPLC peaks appeared, which all corresponded to SA-Lys adducts. TLC analysis of SA-Lys showed that SA-Lys could form as many as seven different adducts. No SA-adduct peaks were observed in HPLC in urines from normal subjects, patients with other forms of aminoaciduria, or patients with the nephrotic syndrome. In addition to amino acids and proteins, SA reacted with reduced glutathione (GSH) and formed a stable adduct. These findings suggest that SA adduct formation with amino acids, GSH, and proteins is a significant process occurring in tyrosinemia, and may account for certain of the pathologic findings in this hereditary disorder.
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PMID:Hereditary tyrosinemia. Formation of succinylacetone-amino acid adducts. 392 1

Uptake and metabolism of the cysteinyl leukotrienes C4 and E4 (LTC4 and LTE4) were studied in AS-30D hepatoma cell suspensions and compared with rat hepatocytes. The hepatoma cells were deficient in the uptake of [3H]LTC4 and [3H]LTE4 but took up, in control experiments, L-[14C]glutamine and [14C]adenosine in a time-dependent manner. By contrast, isolated hepatocyte suspensions incubated under the same conditions took up [3H]LTC4 and [3H]LTE4 as well as L-[14C]glutamine and [14C]adenosine. The hepatoma cells deficient in the uptake of cysteinyl leukotrienes metabolized extracellular [3H]LTC4 to [3H]LTD4 and to [3H]LTE4. Addition of acivicin, an inhibitor of gamma-glutamyltransferase, largely prevented metabolism of [3H]LTC4 by the hepatoma cells. Sonication of the cells did not enhance the formation of [3H]LTD4 and [3H]LTE4 from [3H]LTC4. We conclude that ectoenzymes of AS-30D hepatoma cells catalyze the conversion of LTC4 to LTE4 via LTD4. As compared to hepatocytes, these neoplastic cells have lost the uptake system for cysteinyl leukotrienes and may serve in studies on leukotriene metabolism by cell-surface enzymes.
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PMID:Leukotriene C4 metabolism by hepatoma cells deficient in the uptake of cysteinyl leukotrienes. 394 67

The antitumor drug acivicin, L-(alpha S,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid, irreversibly inactivated in vivo formylglycinamidine ribonucleotide synthetase (FGAM synthetase, EC 6.3.5.3) in transplantable rat hepatoma 3924A while the activity in host liver remained unchanged. At acivicin doses of 1.0 and 5.0 mg/kg body weight, enzyme activity in the hepatoma decreased to 26 and 5%, respectively, after 2 hr. The activity of the in vivo inactivated hepatoma 3924A enzyme could not be restored by gel filtration or 40 hr of dialysis. In the absence of L-glutamine, acivicin in vitro inactivated both liver and hepatoma FGAM synthetase in a time-dependent fashion, with an inactivation constant Kinact = 66 microM and a minimum inactivation half-time T = 1.0 min. In the presence of L-glutamine, competitive inhibition was observed with a Ki = 5 microM. Protection against in vitro inactivation was observed in the presence of 1 mM L-glutamine, suggesting that L-glutamine concentrations are important in the selective toxicity of acivicin on hepatoma cells in vivo. Irreversible inhibition of FGAM synthetase by acivicin is consistent with the view that this antibiotic is an active site-directed affinity analog of L-glutamine and indicates that this enzyme is a sensitive target of acivicin action.
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PMID:In vivo inactivation of formylglycinamidine ribonucleotide synthetase in rat hepatoma. 396 25

Carbamoyl-phosphate synthetase II (glutamine hydrolyzing, EC 6.3.5.5) (synthetase II), the rate-limiting enzyme of de novo uridine monophosphate biosynthesis, was purified 230-fold to apparent homogeneity from rapidly growing rat hepatoma 3924A. The antiserum (produced in rabbits against purified hepatoma 3924A enzyme) yielded a single precipitin line with crude and partially purified synthetase II of normal liver and three hepatomas. In hepatomas of slow (20), intermediate (7787), and rapid (3924A) growth rates, synthetase II activity was elevated 1.5-, 2.3-, and 7.9-fold, and the amount of antiserum required to inactivate the activity was 1.6-, 2.3-, and 8.2-fold higher than that in normal liver. Thus the increase in synthetase II activity in the tumors was due to an elevation in the amount of the synthetase II enzyme protein.
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PMID:Increased carbamoyl-phosphate synthetase II concentration in rat hepatomas: immunological evidence. 402 25

A 125-kilodalton (kDa) phosphoprotein was isolated from nucleoli of Novikoff hepatoma cells in the presence of various inhibitors of proteases, alkaline phosphatase, and RNase. This protein was the most highly phosphorylated protein found thus far in the nucleolus. The half-life of [32P]phosphate in the 125-kDa phosphoprotein was approximately 60 min. Amino acid analysis of the protein showed it had a high serine content (15.5 mol %), a high glutamine plus glutamic acid content (15.5 mol %), and a high lysine content (10.3 mol %). Phosphoserine was the only phosphorylated amino acid identified. After alkaline hydrolysis of the 32P-labeled protein, ribonucleotides were found which accounted for approximately 8.5% of the [32P]phosphate. After cytidine 3',5'-[32P]diphosphate ([32P]pCp) labeling by RNA ligase, several oligoribonucleotide sequences were purified including GGGCOH and GGGGCOH. The binding of oligonucleotides to peptides was stable under denaturing fractionation conditions including 6 M urea treatment and incubation at 100 degrees C for 10 min in sodium dodecyl sulfate and beta-mercaptoethanol. Furthermore, when nucleotide-peptide complex was treated with ribonuclease T2 followed by snake venom phosphodiesterase, the junctional nucleotide pCp was released. These results suggest that one or more ribonucleotides are covalently bound to the 125-kDa phosphoprotein.
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PMID:Isolation and characterization of a 125-kilodalton rapidly labeled nucleolar phosphoprotein. 408 83


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