Particulate and Free Hexokinase in Fetal Rat Liver

Hommes, F. A.; Everts, Regula

doi:10.1159/000241072

Cited by 8 publications

(4 citation statements)

References 16 publications

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“…Particulate hexokinase activity had been reported for most rat tissues (Crane & Sols, 1953;Colowick, 1973), including foetal and neonatal liver Hommes & Everts, 1978), and for the liver from other mammals (Ureta et al, 1981), but not for adult rat liver (Siekevitz & Potter, 1955;Ureta et al, 1975). The small amount of particulate hexokinase existing in the liver and the high concentration of detergent required for its solubilization could explain why it had not been previously detected.…”

Section: Discussionmentioning

confidence: 98%

All hexokinase isoenzymes coexist in rat hepatocytes

Reyes¹,

Cárdenas²

1984

Biochemical Journal

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The cellular distribution of hexokinase isoenzymes, N-acetylglucosamine Kinase and pyruvate kinases in rat liver was studied. Hepatocytes and non-parenchymal cells with high viability and almost no cross-contamination were obtained by perfusion in situ of the liver with collagenase, with the use of an enriched cell-culture medium in all steps of cell isolation. Separation of hexokinase isoenzymes was done by DEAE-cellulose chromatography, and enzyme activities were measured by a specific radioassay. Cytosol from isolated hepatocytes contained high-affinity hexokinases A, B and C, in addition to hexokinase D. The last-mentioned represented about 95% of total glucose-phosphorylating activity. Only hexokinase A was found associated t the particulate fraction. Isolated non-parenchymal cells contained only hexokinases A, B and C. N-Acetylglucosamine kinase was measured with a specific radioassay and was found as a single enzyme form in both hepatocytes and non-parenchymal cells, with higher activities in the former. Pyruvate kinase isoenzyme L was present only in the hepatocytes and isoenzyme K only in the non-parenchymal liver cells, confirming that they are good cellular markers.

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Section: Discussionmentioning

confidence: 98%

All hexokinase isoenzymes coexist in rat hepatocytes

Reyes¹,

Cárdenas²

1984

Biochemical Journal

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“…It has been shown by Ureta et al (1975) and subsequently by Hommes & Everts (1978), that in foetal rat liver more than 50% of the hepatocyte hexokinase activity appears to be bound to mitochondria; this binding of hexokinase by mitochondria decreases to very low levels within 20 days after birth (Ureta et al, 1975). During this time the total hexokinase activity per g of liver also diminishes drastically (Ureta et al, 1975).…”

Section: Low Mitochondrial Adenine Nucleotide Concentration In Vivo and High A Tp Transport Activity In Vitromentioning

confidence: 98%

“…During this time the total hexokinase activity per g of liver also diminishes drastically (Ureta et al, 1975). Both these groups of workers have suggested that the binding of hexokinase to mitochondria is not only a property of the changing hexokinase isoenzymes, but may also depend on some specific property of the mitochondrial membranes, which also change their characteristics during development (Ureta et al, 1975;Hommes & Everts, 1978). This binding of hexokinase to the mitochondria and the greater amount of hexokinase present in foetal rat liver may be one of the factors contributing to the low adenine nucleotide concentration of foetal rat liver mitochondria.…”

Section: Low Mitochondrial Adenine Nucleotide Concentration In Vivo and High A Tp Transport Activity In Vitromentioning

confidence: 99%

The transport and accumulation of adenine nucleotides during mitochondrial biogenesis

Pollak¹,

Sutton²

1980

Biochemical Journal

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The atractyloside-insensitive accumulation of adenine nucleotides by rat liver mitochondria (as opposed to the exchange-diffusion catalysed by the adenine nucleotide translocase) has been measured by using the luciferin/luciferase assay as well as by measuring [14C]ATP uptake. In foetal rat liver mitochondria ATP is accumulated more rapidly than ADP, whereas AMP is not taken up. The uptake of ATP occurs against a concentration gradient, and the rate of ATP uptake is greater in foetal than in adult rat liver mitochondria. The accumulated [14C]ATP is shown to be present within the mitochondrial matrix space and is freely available to the adenine nucleotide translocase for exchange with ATP present in the external medium. The uptake is specific for ATP and ADP and is not inhibited by adenosine 5'-[beta gamma-imido] triphosphate, GTP, CTP, cyclic AMP or Pi, whereas dATP and AMP do inhibit ATP accumulation. The ATP accumulation is also inhibited by carbonyl cyanide m-chlorophenylhydrazone, KCN and mersalyl but is insensitive to atractyloside. The ATP uptake is concentration-dependent and exhibits Michaelis-Menten kinetics. The divalent cations Mg2+ and Ca2+ greatly enhance ATP accumulation, and the presence of hexokinase inhibits the uptake of ATP by foetal rat liver mitochondria. These latter effects provide an explanation for the low adenine nucleotide content of foetal rat liver mitochondria and the rapid increase that occurs in the mitochondrial adenine nucleotide concentration in vivo immediately after birth.

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“…Tumors over-express the high affinity hexokinase 2, which strongly interacts with the mitochondrial ANT-VDAC-PTP complex. In this position, close to the ATP/ADP exchanger (ANT), the hexokinase receives efficiently its ATP substrate [6,7]. As long as hexokinase occupies this mitochondria site, glycolysis is efficient.…”

Section: Abnormal Metabolism Of Tumors a Selective Advantagementioning

confidence: 99%

The metabolic advantage of tumor cells

2011

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1- Oncogenes express proteins of "Tyrosine kinase receptor pathways", a receptor family including insulin or IGF-Growth Hormone receptors. Other oncogenes alter the PP2A phosphatase brake over these kinases.2- Experiments on pancreatectomized animals; treated with pure insulin or total pancreatic extracts, showed that choline in the extract, preserved them from hepatomas.Since choline is a methyle donor, and since methylation regulates PP2A, the choline protection may result from PP2A methylation, which then attenuates kinases.3- Moreover, kinases activated by the boosted signaling pathway inactivate pyruvate kinase and pyruvate dehydrogenase. In addition, demethylated PP2A would no longer dephosphorylate these enzymes. A "bottleneck" between glycolysis and the oxidative-citrate cycle interrupts the glycolytic pyruvate supply now provided via proteolysis and alanine transamination. This pyruvate forms lactate (Warburg effect) and NAD+ for glycolysis. Lipolysis and fatty acids provide acetyl CoA; the citrate condensation increases, unusual oxaloacetate sources are available. ATP citrate lyase follows, supporting aberrant transaminations with glutaminolysis and tumor lipogenesis. Truncated urea cycles, increased polyamine synthesis, consume the methyl donor SAM favoring carcinogenesis.4- The decrease of butyrate, a histone deacetylase inhibitor, elicits epigenic changes (PETEN, P53, IGFBP decrease; hexokinase, fetal-genes-M2, increase)5- IGFBP stops binding the IGF - IGFR complex, it is perhaps no longer inherited by a single mitotic daughter cell; leading to two daughter cells with a mitotic capability.6- An excess of IGF induces a decrease of the major histocompatibility complex MHC1, Natural killer lymphocytes should eliminate such cells that start the tumor, unless the fever prostaglandin PGE2 or inflammation, inhibit them...

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Particulate and Free Hexokinase in Fetal Rat Liver

Cited by 8 publications

References 16 publications

All hexokinase isoenzymes coexist in rat hepatocytes

All hexokinase isoenzymes coexist in rat hepatocytes

The transport and accumulation of adenine nucleotides during mitochondrial biogenesis

The metabolic advantage of tumor cells

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