Some factors affecting carbohydrate metabolism in hepatic tissues of different growth rates

Lea, Michael A.; Sasovetz, D.; Morris, H. P.

doi:10.1002/ijc.2910040414

Cited by 11 publications

(4 citation statements)

References 12 publications

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“…A short review of reported changes in glucose metabolism in response to hydroxyurea treatment (a potent DNA/RNA synthesis inhibitor also used to treat CML) is given here to address whether decreased glucose uptake, activation, and oxidation are unique to direct targeting of the kinase activity of Bcr-Abl by STI571. Glucokinase activity of regenerating liver showed a dose-dependent increase (24 h) or no change (48 and 96 h) after 250 and 1000 mg/kg hydroxyurea treatment in rats (26). In the same study, hexokinase activity was decreased after 250 mg/kg hydroxyurea treatment but increased after 1000 mg/kg hydroxyurea treatment in hepatoma 7777 and 3924-A cells.…”

Section: Discussionmentioning

confidence: 70%

Gleevec (STI571) Influences Metabolic Enzyme Activities and Glucose Carbon Flow toward Nucleic Acid and Fatty Acid Synthesis in Myeloid Tumor Cells

Boren

Cascante

Marín

et al. 2001

Journal of Biological Chemistry

171

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Chronic myeloid leukemia cells contain a constitutively active Bcr-Abl tyrosine kinase, the target protein of Gleevec (STI571) phenylaminopyrimidine class protein kinase inhibitor. Here we provide evidence for metabolic phenotypic changes in cultured K562 human myeloid blast cells after treatment with increasing doses of STI571 using [1,2-13 C 2 ]glucose as the single tracer and biological mass spectrometry. In response to 0.68 and 6.8 M STI571, proliferation of Bcr-Abl-positive K562 cells showed a 57% and 74% decrease, respectively, whereas glucose label incorporation into RNA decreased by 13.4% and 30.1%, respectively, through direct glucose oxidation, as indicated by the decrease in the m 1 /⌺m n ratio in RNA. Based on the in vitro proliferation data, the IC 50 of STI571 in K562 cultures is 0.56 M. The decrease in 13 C label incorporation into RNA ribose was accompanied by a significant fall in hexokinase and glucose-6-phosphate 1-dehydrogenase activities. The activity of transketolase, the enzyme responsible for nonoxidative ribose synthesis in the pentose cycle, was less affected, and there was a relative increase in glucose carbon incorporation into RNA through nonoxidative synthesis as indicated by the increase in the m 2 /⌺m n ratio in RNA. The restricted use of glucose carbons for de novo nucleic acid and fatty acid synthesis by altering metabolic enzyme activities and pathway carbon flux of the pentose cycle constitutes the underlying mechanism by which STI571 inhibits leukemia cell glucose substrate utilization and growth. The administration of specific hexokinase/glucose-6-phosphate 1-dehydrogenase inhibitor anti-metabolite substrates or competitive enzyme inhibitor compounds, alone or in combination, should be explored for the treatment of STI571-resistant advanced leukemias as well as that of Bcr-Abl-negative human malignancies.

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Section: Discussionmentioning

confidence: 70%

Gleevec (STI571) Influences Metabolic Enzyme Activities and Glucose Carbon Flow toward Nucleic Acid and Fatty Acid Synthesis in Myeloid Tumor Cells

Boren

Cascante

Marín

et al. 2001

Journal of Biological Chemistry

171

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“…Their effects are not restricted to this enzyme; they also inhibit NAD glycohydrolase (Masmoudi and Mandel, 1987). By inhibiting NAD glycohydrolase, they may affect some events of cellular metabolism (Lea et al, 1969). ATP was shown to be more effective in inhibiting NAD glycohydrolase in nonsynaptic mitochondria.…”

Section: Discussionmentioning

confidence: 99%

ADP‐Ribosylation of Highly Purified Rat Brain Mitochondria

Masmoudi¹,

Islam²,

Mandel³

1988

Journal of Neurochemistry

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Highly purified synaptic and nonsynaptic mitochondria were prepared from rat brain, and their ADP-ribosyl transferase and NAD glycohydrolase activities were investigated. Data show that there is no significant difference in ADP-ribosyl transferase activity between these two types of subcellular preparations. However, NAD glycohydrolase activity appeared to be much higher in nonsynaptic mitochondria. The specific activity of both enzymes was investigated in the presence of the inhibitor nicotinamide or its analogue 3-aminobenzamide or other adenine nucleotides, such as ATP or ADP-ribose. The inhibitory effect of nicotinamide or 3-aminobenzamide on ADP-ribosyl transferase appears rather weak compared with their effect on NAD glycohydrolase activity. However, ADP-ribose and ATP appeared more effective in inhibiting ADP-ribosyl transferase. Our results provide evidence for the existence of ADP-ribosyl transferase activity in rat brain mitochondria. When NAD glycohydrolase was inhibited totally by nicotinamide, the transfer of ADP-ribose from NAD to mitochondrial proteins still occurred. The chain length determinations show that the linkage of ADP-ribose to mitochondrial proteins is oligomeric.

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“…Itis more likely that the lowered content of UDPIglucose is caused by a decreased rate of synthesis. It is known tha-t the hexokinase activity increases (Lea et al, 1970) and phosphoglucomutase activity remains constant (Weber & Cantero, 1957) after partial hepatectomy. Moreover, the coenzyme UTP, necessary for the synthesis of UDP-glucose, increases by 50 % within 3 h after partial hepatectomy (Bucher & Swaffield, 1969).…”

Section: Discussionmentioning

confidence: 99%

Galactose metabolism in regenerating rat liver

Bauer¹,

Hassels²,

Reutter³

1976

Biochemical Journal

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1. Rats trained on a controlled lighting and feeding schedule were subjected to partial hepatectomy or sham operation. 2. After a large period of about 6h the activity of UDP-galactose 4-epimerase increased threefold, reaching a maximum 4 days after partial hepatectomy, and returned to normal values within a fortnight. 3. The enzyme pattern of the UDP-galactose-glycoprotein galactosyltransferase was biphasic, one peak appearing at 20 h, the second at 72 h after partial hepatectomy. 4. The rise in enzyme activities could be blocked by the injection of actinomycin D, and the Km values for UDP-glucose and UDP-galactose were nearly identical in regenerating and adult liver. It is therefore concluded that the increase in enzyme activity is due to synthesis de novo of enzyme protein.

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Some factors affecting carbohydrate metabolism in hepatic tissues of different growth rates

Cited by 11 publications

References 12 publications

Gleevec (STI571) Influences Metabolic Enzyme Activities and Glucose Carbon Flow toward Nucleic Acid and Fatty Acid Synthesis in Myeloid Tumor Cells

Gleevec (STI571) Influences Metabolic Enzyme Activities and Glucose Carbon Flow toward Nucleic Acid and Fatty Acid Synthesis in Myeloid Tumor Cells

ADP‐Ribosylation of Highly Purified Rat Brain Mitochondria

Galactose metabolism in regenerating rat liver

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