Search PubMed⌕ Search

Biomedical subjects

E Eigenbrodt

Publications and source records attributed to E Eigenbrodt.

At least 19 recordsLinked to original sources
PubMed1997

Effect of extracellular AMP on cell proliferation and metabolism of breast cancer cell lines with high and low glycolytic rates.

In differentiated tissues, such as muscle and brain, increased adenosine monophosphate (AMP) levels stimulate glycolytic flux rates. In the breast cancer cell line MCF-7, which characteristically has a constantly high glycolytic flux rate, AMP induces a strong inhibition of glycolysis. The human breast cancer cell line MDA-MB-453, on the other hand, is characterized by a more differentiated metabolic phenotype. MDA-MB-453 cells have a lower glycolytic flux rate and higher pyruvate consumption than MCF-7 cells. In addition, they have an active glycerol 3-phosphate shuttle. AMP inhibits cell proliferation as well as NAD and NADH synthesis in both MCF-7 and MDA-MB-453 cells. However, in MDA-MB-453 cells glycolysis is slightly activated by AMP. This disparate response of glycolytic flux rate to AMP treatment is presumably caused by the fact that the reduced NAD and NADH levels in AMP-treated MDA-MB-453 cells reduce lactate dehydrogenase but not cytosolic glycerol-3-phosphate dehydrogenase reaction. Due to the different enzymatic complement in MCF-7 cells, proliferation is inhibited under glucose starvation, whereas MDA-MB-453 cells grow under these conditions. The inhibition of cell proliferation correlates with a reduction in glycolytic carbon flow to synthetic processes and a decrease in phosphotyrosine content of several proteins in both cell lines.

Adenosine Monophosphate↗
PubMed1996

Studies on associations of glycolytic and glutaminolytic enzymes in MCF-7 cells: role of P36.

Isoelectric focusing of MCF-7 cell extracts revealed an association of the glycolytic enzymes glyceraldehyde 3-phosphate-dehydrogenase, phosphoglycerate kinase, enolase, and pyruvate kinase. This complex between the glycolytic enzymes is sensitive to RNase. p36 could not be detected within this association of glycolytic enzymes; however an association of p36 with a specific form of malate dehydrogenase was found. In MCF-7 cells three forms of malate dehydrogenase can be detected by isoelectric focusing: the mitochondrial form with an isoelectric point between 8.9 and 9.5, the cytosolic form with pl 5.0, and a p36-associated form with pl 7.8. The mitochondrial form comprises the mature mitochondrial isoenzyme (pl 9.5) and its precursor form (pl 8.9). Refocusing of the pl 7.8 form of malate dehydrogenase also gave rise to the mitochondrial isoenzyme. Thus, the pl 7.8 form of malate dehydrogenase is actually the mitochondrial isoenzyme retained in the cytosol by the association with p36. Addition of fructose 1,6-bisphosphate to the initial focusing column induced a quantitative shift of the pl 7.8 form of malate dehydrogenase to the mitochondrial forms (pl 8.9 and 9.5). In MCF-7 cells p36 is not phosphorylated in tyrosine. Kinetic measurements revealed that the pl 7.8 form of malate dehydrogenase has the lowest affinity for NADH. Compared to both mitochondrial forms the cytosolic isoenzyme has a high capacity when measured in the NAD --> NADH direction (malate --> oxaloacetate direction). The association of p36 with the mitochondrial isoenzyme may favor the flow of hydrogen from the cytosol into the mitochondria. Inhibition of cell proliferation by AMP which leads to an inhibition of glycolysis has no effect on complex formation by glycolytic and glutaminolytic enzymes in MCF-7 cells. AMP treatment leads to an activation of malate dehydrogenase, which correlates with the increase of pyruvate and the decrease of lactate levels, but has no effect on the distribution of the various malate dehydrogenase forms.

Adenosine Monophosphate↗
PubMed1994

L- and M2-pyruvate kinase expression in renal cell carcinomas and their metastases.

Using immunohistochemical and enzyme biochemical methods we investigated the expression of L- and M2-pyruvate kinase (PK) in normal renal tissue, renal cell carcinomas (RCCs; of clear cell, chromophilic cell and mixed cell type) and RCC metastases. L-PK was expressed in the proximal tubules of normal renal tissue and, to a variable extent, in 23/25 primary RCCs, in 1 RCC recurrence and in 10 RCC metastases. Staining intensity and percentage of stained tissue did not correlate with tumour grade. One renal oncocytoma and all extrarenal malignancies examined lacked L-PK immunoreactivity. M2-PK was mainly expressed in the distal tubules of the normal kidney and was found in all renal tumours as well as extrarenal malignancies. Quantitative biochemical investigations yielded a two- to seventeen-fold increase in PK activity in RCCs compared to the normal renal cortex taken from the same patient, whereas fructose-1,6-bisphosphatase and cytosolic glycerol-3-phosphate dehydrogenase activity was dramatically lower in RCCs. Otherwise, the activity of all other enzymes investigated (glucose-6-phosphate dehydrogenase, enolase and lactate dehydrogenase) was not significantly changed in the RCCs. The immunocytochemical results suggest that L-PK is a useful marker for RCC and its metastases, if acetone-fixed tissue is available. The quantitative changes of the concentration of PK and other enzymes in RCCs when compared with normal renal tissue probably reflect metabolic alterations related to tumour growth.

Carcinoma, Renal Cell↗
PubMed1994

Expression of L- and M2-pyruvate kinases in proliferating oval cells and cholangiocellular lesions developing in the livers of rats fed a methyl-deficient diet.

Male outbred Sprague-Dawley rats were fed a choline-deficient diet containing 0.1% w/w DL-ethionine (CDE) for up to 22 weeks. The expression of the pyruvate kinase isoenzymes L (L-PK) and M2 (M2-PK) was immunohistochemically analyzed in liver slices from rats killed 4, 10, 14 and 22 weeks after starting the treatment. M2-PK was detected in bile duct epithelial cells of untreated rats and in proliferating oval cells, cholangiofibroses and cholangiofibromas of CDE-fed animals. Thus, M2-PK can be viewed as a positive marker of the bile duct epithelial/oval cell compartment. L-PK, a parenchymal cell-specific protein in untreated rat liver, was not present in proliferating oval cells, but was consistently observed in cells that were part of the ductal structures in the cholangiofibroses and cholangiofibromas. Based on their morphology, the L-PK-positive duct cells were undoubtedly part of the bile duct epithelial cell lineage and no L-PK-positive hepatocyte-like cells were observed in the ducts. Hence, this study clearly shows that the mere presence of a liver parenchymal cell marker in cells of the bile duct epithelial/oval cell compartment does not necessarily preclude that these cells are undergoing a differentiation into preneoplastic parenchymal cells, as has previously been suggested.

Animals↗
PubMed1993

The influence of storage time on the nucleotide concentration of canine platelets.

Nucleotide concentrations of canine platelets during storage for 50 days were determined to find out the variation in the concentration of various nucleotides in canine platelets during storage at +4 degrees C for 50 days. Platelets of 3 dogs were stored in whole blood in PVC bags containing CPDA-1 stabilizer. The bags were kept at 4 degrees C for 50 days. Changes in the energy metabolism of the platelets during storage were determined by successive measurements of the following nucleotides: adenosine-diphosphate (ADP), adenosine-tri-phosphate (ATP) and guanosine-tri-phosphate (GTP). In preparation for the measurement of their nucleotide content, the platelets were isolated from the blood at regular intervals and their membranes destroyed by deep freezing, thawing, double sonification in ice and protein precipitation with perchloric acid. The concentration of nucleotides within the platelets was determined by "High Pressure Liquid Chromatography" (HPLC). ADP, ATP and GTP were identified in the peak areas of the HPLC using 3 different techniques: comparison of retention time of standard nucleotide solutions as control samples, enzyme tests and thin layer chromatography. Adenosine-mono-phosphate (AMP), adenosine, hypoxanthine and inosine mono 5'-phosphate (IMP) were not found in dog platelets. Platelet ATP concentration decreased significantly during 50 days of storage (p < 0.001), and was reduced to 24% of the concentration measured after 1 hour of storage on day 50. ADP concentration also dropped significantly during 50 days of storage (p < 0.001). On day 50 the average ADP concentration was reduced to about 34% of the concentration measured after 1 hour of storage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Cell cycle-associated expression of M2-type isozyme of pyruvate kinase in proliferating rat thymocytes.

During a complete cell cycle of rat thymocytes stimulated by concanavalin A and interleukin 2, the activity and mRNA level of pyruvate kinase reached a maximum (8-12-fold increase) 48 h after stimulation coinciding with the S-phase of the cell cycle. Increases of cellular enzyme activity, pyruvate kinase protein, and mRNA levels are correlated up to 48 h of culture. Afterwards pyruvate kinase activity and mRNA levels decrease, whereas the pyruvate kinase protein continues to increase throughout mitosis. This change of specific pyruvate kinase activity points to a posttranslational modification of the enzyme besides its transcriptional regulation. The presence of the M2-type isozyme was determined by the following methods: (a) native cellulose acetate electrophoresis and activity staining, (b) Northern blot hybridization with M1- and M2-specific cDNA probes, and (c) determination of kinetic parameters. The isozyme pattern did not change during the cell cycle progression. The induction of pyruvate kinase is completely abolished by 2-difluoromethylornithine-mediated polyamine depletion. However, the proportion of hybridizable pyruvate kinase mRNA was not affected. These data suggest the requirement of polyamines for efficient translation rather than transcription during cell growth.

Animals↗
PubMed1992

In vitro effect of extracellular AMP on MCF-7 breast cancer cells: inhibition of glycolysis and cell proliferation.

MCF-7 human breast cancer cells propagated in vitro were treated with adenosine derivatives added to the culture medium. The effects on cell proliferation, glycolysis, and glutaminolysis were investigated. Of all adenosine derivatives tested, AMP was the most efficient inhibitor of cell proliferation. In AMP-treated cells, DNA synthesis decreased, whereas RNA and protein syntheses rose normally with time. In terms of carbohydrate metabolism, lactate production from glucose was drastically reduced; therefore, most of lactate produced must have been derived from glutamine. Increases in the enzyme activities involved in glutamate degradation and in the malate-aspartate shuttle were observed. In contrast, actual glycolytic flux rates declined, whereas key glycolytic enzyme activities increased. Metabolites such as fructose 1,6-bisphosphate and pyruvate accumulated in AMP-arrested cells. Based on the lowered NAD level in the AMP-treated cells, lactate dehydrogenase, but not malate dehydrogenase, was impaired; thereby the whole of glycolysis was inhibited. In compensation, glutamine catabolism was increased. NAD concentrations fell drastically because of the known inhibition of P-ribose-PP synthesis through heightened intracellular AMP levels. A hypothetical metabolic scheme to explain these results and to show how extracellular AMP may influence carbohydrate metabolism and cell proliferation is presented.

Adenosine Monophosphate↗
PubMed1992

Immunohistological demonstration of pyruvate kinase isoenzyme type L in rat with monoclonal antibodies.

Four monoclonal antibodies (MAb) specific for the L-type isoenzyme of rat pyruvate kinase (L-PK) were produced and characterized. They detect at least two different epitopes of the isoenzyme, as shown in interference binding assay and Western blot analysis after peptide mapping. The MAb were used in immunohistology to demonstrate the L-PK isoenzyme in paraffin-embedded normal rat tissues. L-PK was found only in hepatocytes, kidney proximal tubules, islet cells of pancreas, and epithelial cells of the villi of small intestine. The content of L-PK in hepatocytes was often lower in the periportal areas as compared with the periveneous zone. In kidneys a clearcut difference in L-PK content and distribution existed between male and female rats. Male animals possessed more L-PK in the kidney cortex than females. The L-PK content in the inner cortical zone (straight proximal tubules) was higher than in the outer cortical zone (convoluted proximal tubules) in kidneys of males. In contrast, female rats displayed less L-PK in the inner than in the outer cortical zone of the kidneys. Only some of them exhibited the same amount of the isoenzyme in both parts of the kidney proximal tubules.

Animals↗
PubMed1992

Hormone-sensitive carbohydrate metabolism in rat hepatocyte-hepatoma hybrid cells.

Hepatocyte-hepatoma hybrid cells were obtained by fusion of hepatocytes from adult rats and Fao hepatoma cells in the presence of polyethylene glycol. These hybrids were called hepatocytoma cells. The preservation of liver-specific enzyme activities and metabolic functions was studied in the hybrid clone 1E3. 1) The proliferating hepatocytoma cells formed monolayers presenting morphological similarity to primary cultures of hepatocytes. 2) In contrast to Fao hepatoma cells, activities of all gluconeogenic key enzymes were preserved at normal or reduced levels. 3) Lactate-dependent glucose formation was maintained at a state reduced to 36% of the gluconeogenesis in hepatocytes; no glucose formation was detected in Fao hepatoma cells. 4) The activity of the liver-specific glucokinase was reduced in hepatocytoma cells, but it was still present in contrast to Fao cells. The liver-specific isoenzyme pyruvate kinase type L was replaced by the isoenzyme type M2. 5) Gluconeogenic and glycolytic enzyme activities were regulated in hepatocytoma cells by glucagon (0.1 microM) and by insulin (0.1 microM). 6) The genome of hepatocytoma cells and its expression were stable for at least one year, when spontaneously dedifferentiating cells were removed by recloning in hypoxanthine-aminopterine-thymidine (HAT) medium.

Animals↗
PubMed1992

Double role for pyruvate kinase type M2 in the expansion of phosphometabolite pools found in tumor cells.

As a common characteristic of tumor cells, as well as of normal proliferating cells in the G1-phase of cell cycle, one finds constitutive high levels of all the glycolytic metabolites arising between glucose 6-phosphate and phosphoenolpyruvate. Thus, it is that the phosphometabolites fructose 1,6-bisphosphate, ribose 5-P, P-ribose-PP, NAD, GTP, CTO, UTP, UDP-glucose, glycerol 3-P, glycerol phosphocholine and glycerol phosphoethanolamine are useful in the 31P-nuclear magnetic resonance (NMR) detection of solid tumors in animals and man. This expansion of phosphometabolites is achieved during tumor formation as a result of reductions in levels of enzymes degrading phosphometabolites, owing to the decline in the glycerol 3-P hydrogen shuttle, and as a consequence of alterations in the glycolytic isoenzyme equipment. Tumor cells typically express a particular isoenzyme of pyruvate kinase called type M2 (K) at high levels. This isoenzyme is subject to a complex regulation by amino acids, by fructose 1,6-bisphosphate, and by hormonal- and oncogene-dependent phosphorylation. Pyruvate kinase type M2 is a substrate for the oncogene encoded PP60v-src-tyrosine kinase. A drastic decrease in the affinity for its substrate phosphoenolpyruvate found after transformation by the src-oncogene can be explained as a consequence of the phosphorylation of pyruvate kinase in serine and tyrosine. These phosphorylations induce the breakdown of tetrameric pyruvate kinase to the trimeric and dimeric forms. Unlike the tetrameric form, the dimeric form as a low affinity for phosphoenolpyruvate. Partial inactivation of pyruvate kinase and enolase on the one hand, and a hyperactivation of hexokinase and phosphofructokinase on the other hand, lead to an expansion of all metabolites. Only when these metabolites attain high levels, thereby assuring a sufficient supply of metabolites for RNA, DNA, lipid, and complex carbohydrate synthesis, can cell proliferation proceed. This accumulation of metabolites in the G1-phase cells has been termed a "metabolic budget system" because it senses not only the actual nutrient levels, but also the supply over a period of time. Monoclonal antibodies specific for the dimeric form of pyruvate kinase type M2 can be used for the immunohistological detection of tumor cells. The amount of the dimeric form in tumor cells closely correlates with the degree of malignancy and can be used for a nonspecific detection of tumors based on assays performed with patient's plasma.

Adenosine Triphosphate↗
PubMed1990

Di(2-ethylhexyl)phthalate alters carbohydrate enzyme activities and foci incidence in rat liver.

The effect of di(2-ethylhexyl)phthalate (DEHP) on diethylnitrosamine (DEN)-initiated preneoplastic liver lesions with expression of gamma-glutamyltranspeptidase (GGTase) and loss of adenosine triphosphatase (ATPase) as well as alterations of hepatic carbohydrate metabolism in male and female Sprague-Dawley rats have been investigated. Two treatment schedules have been compared with respect to their sensitivity by the histochemical demonstration of preneoplastic islands and by the biochemical determination of alterations in enzyme activities of liver homogenates and of serum, the last indicating hepatotoxicity. For initiation, a single dose of DEN was given, followed by treatment with various doses of DEHP given three times weekly by gavage for 7 or 11 consecutive weeks. As histochemical enzyme markers, the expression of positive GGTase as well as the deficiency in ATPase were used for identification of liver foci. The weanling female rats (protocol A) were found to be more sensitive to the carcinogenic effect of DEN in view of foci incidence than the mature male rats which underwent partial hepatectomy prior to DEN application. The administration of 200 mg DEHP/kg body wt increased the incidence of ATPase-deficient foci in both male and female rats; however, concentrations of 1000 and 2000 mg DEHP/kg decreased the incidence of liver foci. The number of foci with expression of GGTase was only slightly increased in female rats following a DEHP concentration of 50 mg/kg, and 200 mg/kg body wt. DEHP alone did not induce preneoplastic lesions that could be identified by these two markers. Biochemical investigations indicate that DEHP alters the metabolic pattern in liver. An increase of the NADP-linked enzymes glucose-6-phosphate dehydrogenase (G6PDH), malic enzyme, extra-mitochondrial ICDH as well as an enhancement of NAD-dependent alpha-G3PDH and lactate dehydrogenase were found following DEHP administration. On the other hand the glycolytic enzymes pyruvate kinase (PK) and enolase as well as the gluconeogenetic enzyme fructose-1,6-bisphosphatase (FBPase) were significantly reduced. In protocol B (male rats) the reactions of PK, FBPase and malic enzyme were more altered after DEHP exposure than in protocol A, while the activity of G6PDH was more increased in protocol A. Most enzymes being involved in the carbohydrate metabolism are influenced by DEHP in a dose-dependent manner. There was no increase in serum FBPase activity in both male and female rats after DEHP treatment but a reduction of glutamate-oxalate-transaminase and glutamate-pyruvate-transaminase activities was observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphatases↗
PubMed1990

[Immunohistologic photometric quantification of pyruvate kinase content of rat tumors].

86 benign and malignant tumours were investigated histologically and immunohistologically. Staining intensity was measured by scanning-photometry. The computed optical density was digitalized and evaluated with an image analysis system. The results indicate a significantly higher amount of M2-PK in malignant tumours. In the adenocarcinomas of the mammary gland, the content of the M2-PK increased parallel with malignancy (p less than 0.01; r = 0.743). The M2-PK can serve as an indicator of the grade of malignancy in mammary tumours of the rat.

Animals↗
PubMed1989

Comparison of three rat liver foci bioassays--incidence of preneoplastic foci initiated by diethylnitrosamine.

Three rat liver foci bioassays have been compared with respect to their sensitivity by the histochemical demonstration of preneoplastic foci, and by the biochemical determination of alterations in enzyme activities of serum indicating hepatotoxicity. We studied the initiation/promotion schedules according to Oesterle and Deml (A), and according to Pereira (B, Broad Spectrum Protocol), and the initiation/selection protocol according to Tatematsu et al. (C), with diethylnitrosamine (DEN), given as a single initiating dose of 10 and 30 mg/kg body wt respectively. With all schedules Sprague-Dawley rats, either females, 3 weeks old (A), or males, 6 weeks old (B, C) were used. For promotion polychlorinated biphenyls (A) or phenobarbital (B) were administered. Selection was performed with 2-acetylaminofluorene (C). The rats in schemes (B) and (C) underwent partial hepatectomy one day prior to initiation. The number and total area of foci deficient in adenosine-5'-triphosphatase (ATPase) and positive in gamma-glutamyltranspeptidase (GGTase) was evaluated. In the complete schedule with 30 mg of DEN in system (A) foci incidence exceeded that of the other systems by about 7-fold (ATPase) and 2-fold (GGTase) respectively. The lower dose of DEN and all control experiments resulted in a respective lower foci yield. With scheme (C), but not with schemes (A) and (B), e.g. serum fructose-1.6-bisphosphatase and alkaline phosphatase were increased, suggesting liver cell damage. Thus tested with DEN, scheme (A) is most sensitive and causes a low impairment of animals' welfare.

2-Acetylaminofluorene↗
PubMed1989

[Immunohistochemical demonstration of L- and M2-pyruvate kinase in primary renal cell carcinomas and their metastases].

Seventeen renal cell carcinomas (RCC) were classified histologically and investigated for their expression of L- and M2-pyruvate kinase (PK) immunohistochemically. Using monoclonal antibodies we were able to demonstrate L-PK within 15 RCC and two metastases (in thyroid gland and bone) after fixation with aceton and paraffin embedding. In normal renal tissue the enzyme was localized within proximal tubules selectively. No enzyme reaction of L-PK could be demonstrated in renal oncocytoma, thyroid carcinoma, and in carcinomas of renal pelvis and lung. In contrast to this the M2-PK was detectable in all tumors and metastases investigated in this study. The results presented in this paper are able to show that (1) RCC derive from the proximal renal tubules, but not the renal oncocytoma, (2) the detection of L-PK may be helpful for identification of metastases of RCC even if they are undifferentiated and (3) there is an enzyme shift from L-PK to M2-PK within tumor cells of RCC resulting in alteration of glucose utilization from energy supply to syntheses of substrates essential for tumor cells.

Carcinoma, Renal Cell↗
PubMed1988

Pyruvate kinase type M2 is phosphorylated at tyrosine residues in cells transformed by Rous sarcoma virus.

Chicken embryo cells (CECs) contain pyruvate kinase (PK) type M2 (M2-PK). Transformation of CECs by Rous sarcoma virus (RSV) leads to a reduction in the affinity of PK for the substrate phosphoenolpyruvate. In vitro, M2-PK can be phosphorylated at tyrosine residues by pp60v-src, the transforming protein of RSV. To study tyrosine phosphorylation of M2-PK in intact RSV-transformed cells, the protein was immunoprecipitated from 32P-labeled normal and RSV-SR-A-transformed CECs. Phosphoamino acid analysis of immunoprecipitated M2-PK revealed that M2-PK of both normal and transformed CECs contained phosphoserine and small amounts of phosphothreonine. Only M2-PK of transformed CECs contained phosphotyrosine in addition. For enzyme kinetic studies M2-PK was partially purified by chromatography upon DEAE-Sephacel and hydroxyapatite. A decreased affinity for phosphoenolpyruvate was observed 3 h after the onset of transformation using the temperature-sensitive mutant of RSV, ts-NY 68. The kinetic changes were correlated with tyrosine phosphorylation of M2-PK, but there is no direct evidence that they are caused by post-translational modification of the enzyme.

Animals↗
PubMed1987

Histology and histochemistry of the liver of chickens after DENA induced hepatocarcinogenesis and ingestion of low chlorinated biphenyls.

Studies are presented which demonstrate the pathological effects of diethylnitrosamine (DENA) and polychlorinated biphenyls (PCB) in the liver of chickens. DENA, which has been shown to cause tumors in rats and chickens, was tested on 80 laying hens to determine whether changes in the liver during hepatocarcinogenesis were similar to those observed in rats. In addition, the hepatocarcinogenic and cocarcinogenic properties of Clophen C (CC), a technical mixture of low chlorinated biphenyls was tested on chickens. The livers of test animals were examined histologically for preneoplastic and neoplastic lesions. Histochemical methods were used to determine lipid and glycogen contents as well as changes in activity of alkaline phosphatase and gamma-glutamyl-transpeptidase. Putative preneoplastic lesions in the liver were first observed according to the substance and dosage applied as follows: DENA 1 X weekly (group II), beginning on day 258; DENA 2 X weekly (group III), beginning on day 183; and CC + DENA 2 X weekly (group V), beginning on day 231. Application of CC alone did not induce lesions. The concept that CC has cocarcinogenic capability was substantiated by the fact that animals from group V (CC + DENA 2 X weekly) developed twice as many tumors as did animals from group III (DENA 2 X weekly). Additionally, tumors developed earlier in the former group than in the latter.

Animals↗
PubMed1987

Decrease in glucokinase and glucose-6-phosphatase and increase in hexokinase in putative preneoplastic lesions of rat liver.

Preneoplastic liver lesions were produced in female Wistar rats by oral administration of 2-acetylaminofluorene for 165 days succeeded by a carcinogen-free standard diet up to 420 days. During the treatment numerous altered hepatic foci (AHF) and hyperplastic nodules (HN) were detected histochemically by a focal decrease or lack of adenosine-5-triphosphatase and glucose-6-phosphatase (G-6-Pase) activities. In addition, the immunohistochemically demonstrable amount of L-type pyruvate kinase was clearly reduced. The histochemically demonstrated decrease of G-6-Pase was substantiated by microbiochemical determination of the enzyme activity in microdissected material. Moreover, during the experimental period a continuous decrease in glucokinase and an increase in hexokinase was detected microbiochemically within AHF and HN. These alterations indicate a shift in the carbohydrate metabolism from gluconeogenesis to glucose utilization and pentose-phosphate-pathway for biosynthesis of nucleic acids. Beside other oncofetal markers, HK may be used as indicator of the early stages of liver carcinogenesis.

2-Acetylaminofluorene↗