Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The acute and chronic effects of tumour necrosis factor-alpha (TNF-alpha) on leptin production by human preadipocytes, differentiated preadipocytes, and mature adipocytes have been examined by competitive RT-PCR of leptin mRNA and by western blotting. In preadipocytes, secreted leptin was detectable after 5-day incubation in differentiation medium and this increased 4-fold by day 20. TNF-alpha blocked leptin synthesis during differentiation. In differentiated preadipocytes and mature adipocytes, TNF-alpha treatment resulted in time-dependent decreases in mRNA for leptin and glycerol-3-phosphate dehydrogenase (G3PD). In contrast, TNF-alpha (4-8-h treatment) resulted in a 4-fold increase in leptin release. This effect was lost at 24 h and leptin accumulation in culture medium was decreased 24-48 h after TNF-alpha addition. We conclude that TNF-alpha stimulates the release of preformed leptin from human mature adipocytes and existing differentiated preadipocytes, which may contribute to obesity/infection-linked hyperleptinemia, and that TNF-alpha inhibits leptin synthesis via inhibition of preadipocyte differentiation and induction of adipocyte dedifferentiation.
Mol Cell Endocrinol 2000 Jan 25
PMID:Tumour necrosis factor-alpha exerts dual effects on human adipose leptin synthesis and release. 1068 54

Glycolysis is the only ATP-generating process in bloodstream form trypanosomes and is therefore a promising drug target. Inhibitors which decrease significantly the glycolytic flux will kill the parasites. Both computer simulation and experimental studies of glycolysis in bloodstream form Trypanosoma brucei indicated that the control of the glycolytic flux is shared by several steps in the pathway. The results of these analyses provide quantitative information about the prospects of decreasing the flux by inhibition of any individual enzyme. The plasma membrane glucose transporter appears the most promising target from this perspective, followed by aldolase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase and glycerol-3-phosphate dehydrogenase. Non-competitive or irreversible inhibitors would be most effective, but it is argued that potent competitive inhibitors can be suitable, provided that the concentration of the competing substrate cannot increase unrestrictedly. Such is the case for inhibitors that compete with coenzymes or with blood glucose.
Mol Biochem Parasitol 2000 Feb 25
PMID:Metabolic control analysis of glycolysis in trypanosomes as an approach to improve selectivity and effectiveness of drugs. 1074 6

The NAD-dependent glycerol-3-phosphate dehydrogenases (G3PDH, EC 1.1.1.8) of Trypanosoma brucei and Leishmania mexicana are thought to have different roles in carbohydrate metabolism. Here the physicochemical and kinetic properties of natural G3PDH from T. brucei with the recombinant homologue of L. mexicana which share 63% positional identity are compared. Despite their supposed different functions in energy metabolism of the parasites the two G3PDHs have remarkably similar properties, including pH optima and K(m) value for dihydroxyacetone phosphate (DHAP) and NADH in the formation of glycerol 3-phosphate (G3P) and for NAD+ and G3P in the reverse reaction. Both enzymes are subject inhibition by dihydroxyacetone phosphate at concentrations above 0.2 mM and are inhibited by the trypanocidal drugs suramin and melarsen oxide at sub-micromolar concentrations.
Mol Biochem Parasitol 2000 Feb 25
PMID:Comparative study of Leishmania mexicana and Trypanosoma brucei NAD-dependent glycerol-3-phosphate dehydrogenase. 1074 13

Different doses of vitamin B12 (0.25, 0.5, 1, 2 and 4 micrograms/g, injected intraperitoneally for three consecutive days) altered the activities of mitochondrial-alpha-glycerophosphate dehydrogenase (alpha-GPD) and NADP-dependent cytosolic malic enzyme (ME) in the brain of singi fish. The alpha-GPD activity increased at doses of 0.5, 1, 2 and 4 micrograms/g vitamin B12. A dose of 0.5 microgram/g vitamin B12 induced less activity than higher doses. ME activity increased with 1, 2 and 4 micrograms/g of vitamin B12/g. The mitochondrial and cytosolic protein content remained unchanged after vitamin B12 administration. Cycloheximide treatment inhibited the vitamin B12-induced increase in alpha-GPD and ME activity. Thus, vitamin B12 is involved in the induction of some enzymes in fish brain.
Comp Biochem Physiol B Biochem Mol Biol 2000 Apr
PMID:Vitamin B12-induced alterations in activities of alpha-glycerophosphate dehydrogenase and malic enzyme in brain of singi fish, Heteropneustes fossilis (Bloch). 1090 58

Membrane potential-dependent ATP production was measured in mitochondrial fractions of procyclic Trypanosoma brucei using a luciferase based assay. Mitochondria isolated under hypotonic conditions were able to produce ATP using succinate as substrate. The same was observed with mitochondria isolated under isotonic conditions, however, in this case a 6-7-fold higher amount of ATP was produced with glycerol-3-phosphate as substrate. Disruption of the outer membrane of isotonically prepared mitochondria lead to a selective loss of the glycerol-3 phosphate induced ATP production, indicating that glycerol-3-phosphate dehydrogenase is a soluble enzyme of the intermembrane space. Isolation of mitochondria under hypotonic conditions, therefore, results in disruption of the outer membrane, whereas in the organelles isolated under isotonic conditions both the membranes remain intact.
Mol Biochem Parasitol 2000 Nov
PMID:ATP production in isolated mitochondria of procyclic Trypanosoma brucei. 1108 19

Rainbow smelt (Osmerus mordax) can accumulate extreme levels of glycerol in their blood during winter. Low temperatures are required for glycerol accumulation in smelt blood and the enzyme glycerol-3-phosphate dehydrogenase (GPDH) has been suggested to play a role in glycerol production/concentration in this species. In the present study, cDNA sequences encoding glycerol-3-phosphate dehydrogenase (GPDH) from rainbow smelt and Atlantic salmon (Salmo salar) were cloned. The encoded GPDH protein sequences were very similar to one another (88% identity). Using RT-PCR, GPDH mRNA was detected in skin, gill, heart, head kidney, brain and liver from both salmon and smelt obtained in December. However, GPDH was not detected in salmon intestine and spleen or in smelt intestine. Examination of GPDH expression in smelt liver during February by Northern blotting revealed temperature regulation. Elevation of the temperature resulted in a significant decrease in liver GPDH transcript level. Serum glycerol levels decreased concomitantly. These findings suggest a role for GPDH in the accumulation of glycerol in smelt at low temperatures.
Comp Biochem Physiol B Biochem Mol Biol 2001 Mar
PMID:Cloning of glycerol-3-phosphate dehydrogenase cDNAs from two fish species and effect of temperature on enzyme expression in rainbow smelt (Osmerus mordax). 1125 May 35

Phylogenetic utility of the mitochondrial COI (cytochrome oxidase subunit I) and nuclear Gpdh (glycerol-3-phosphate dehydrogenase) genes was studied in the Drosophila melanogaster species group. The rate of substitution was higher in the COI gene than in the Gpdh gene. In addition, multiple substitutions, not only for transitional but also for transversional substitutions, occurred faster in the COI gene. None of the trees obtained using the COI gene supported the well-established monophyly of the ananassae subgroup. In addition, the incongruence length difference test, Templeton test, and partitioned Bremer support revealed that the trees based on the COI data are considerably different from those based on the Gpdh and the combined data set. Thus, the COI gene did not show good phylogenetic performance in the melanogaster group. The present analyses based on the Gpdh gene and the combined data set revealed that the ananassae subgroup branched off first in the melanogaster group followed by the montium subgroup and further by the melanogaster subgroup in contrast to the most recent phylogenetic hypothesis based on Amy multigenes.
Mol Phylogenet Evol 2001 Mar
PMID:Phylogenetic utility of mitochondrial COI and nuclear Gpdh genes in Drosophila. 1127 33

In a new experimental type 2 diabetic syndrome, a 40% reduction of pancreatic beta cells was observed by morphometric analysis. In diabetic islets, as compared to control islets, insulin release was decreased in response to high glucose but not to other stimuli, and total glucose oxidation and utilization were unchanged or slightly reduced. The extent of metabolic and functional impairment appeared proportional to the beta-cell loss. However, a substantial decrease was found in protein level and activity (by 77 and 60%, respectively, versus controls) of mitochondrial FAD-glycerophosphate dehydrogenase (mGDH), the key enzyme of the glycerophosphate shuttle. Interestingly, in diabetic islets, as recently reported for mGDH-deficient transgenic mice, definite functional alterations (mainly in response to D-glyceraldehyde) were only obtained upon pharmacological blockade of the second shuttle (i.e. malate-aspartate) responsible for mitochondrial transfer of reducing equivalents. In conclusion, in this diabetes model with reduction of beta-cell mass, the islets, despite decreased mGDH amount and activity, appear metabolically and functionally active in vitro, likely through the intervention of adaptive mechanisms, yet prone to failure in challenging situations.
Mol Cell Endocrinol 2001 Apr 25
PMID:Metabolic and functional studies on isolated islets in a new rat model of type 2 diabetes. 1132 16

We studied a mouse doubly homozygous for mutations in the genes encoding malic enzyme (EC 1.1.1.40) and cytosolic glycerol phosphate dehydrogenase (EC 1.1.1.8) (cGPD). This mouse, which we call the mmgg mouse and which is the product of intercrosses between the Mod-1 mouse and the BALB/cHeA mouse, lacks activity of both enzymes. Like both parental strains the mmgg mouse is completely normal in appearance. cGPD is one of the two enzymes that catalyze the reactions of the glycerol phosphate shuttle. The activity of the other enzyme of the glycerol phosphate shuttle, mitochondrial glycerol phosphate dehydrogenase (EC 1.1.99.5) (mGPD), is abundant in tissues, such as brain, skeletal muscle and the pancreatic islet, suggesting that the glycerol phosphate shuttle is important in these tissues which rapidly metabolize glucose. Cytosolic malic enzyme activity is important for shuttles which transport NADPH equivalents from mitochondria to the cytosol. The major finding of the study was a highly abnormal metabolite pattern in tissues of the mmgg mouse suggesting a block in the glycerol phosphate shuttle due to cGPD deficiency. The metabolite pattern did not suggest that malic enzyme deficiency caused an abnormality. Tissue levels of glycerol phosphate (low) and dihydroxyacetone phosphate (high) were only abnormal in skeletal muscle. Glycolytic intermediates, situated at or before the triose phosphates in the pathway, such as fructose bisphosphate and glyceraldehyde phosphate were increased depending on the tissue. Taken together with previous extensive data on the mouse deficient only in cGPD, this suggests a block in glycolysis at the step catalyzed by glyceraldehyde phosphate dehydrogenase caused by an abnormally low NAD/NADH ratio resulting from a nonfunctional glycerol phosphate shuttle. Consistent with this idea the lactate/pyruvate ratio was high in skeletal muscle signifying a low cytosolic NAD/NADH ratio. The mmgg mouse was normal in all other factors studied including blood glucose and serum insulin levels, pancreatic islet mass, insulin release from isolated pancreatic islets, as well as the activities of five metabolic enzymes, including mGPD, in liver, kidney, skeletal muscle and pancreatic islets. cGPD enzyme activity was undetectable in pancreatic islets, 0.5% of normal in liver, and 2.1% of normal in kidney and skeletal muscle. Malic enzyme activity was undetectable in these same tissues.
Mol Cell Biochem 2001 Apr
PMID:Survey of normal appearing mouse strain which lacks malic enzyme and Nad+-linked glycerol phosphate dehydrogenase: normal pancreatic beta cell function, but abnormal metabolite pattern in skeletal muscle. 1145 71

The Sn-Glycerol-3-phosphate dehydrogenase (GPDH: NAD+ 2-oxidoreductase, EC 1.1.1.8) gene of C. chinensis was cloned and its nucleotide sequence was analyzed. The gene was obtained by screening a genomic library with Drosophila melanogaster Gpdh and PCR amplification. The 5,126 bp gene obtained is comprised of one 5' untranslated region, eight exons, seven introns, and three 3' untranslated regions. Comparison of Gpdh of D. melanogaster with that of C. chinensis showed a 89.9% identity in the coding region, 70% in the intron, 79% in the entire nucleotide sequence, and 83.2% in the deduced amino acid sequence. The transcription initiation site is located 33 nucleotides upstream of the initiation codon, and the sequence analysis of the promoter region showed TATA and CAAT boxes at the 5' end. The stop codon (TAA) and polyadenylation signal (AATAAA) are located at the 3' end of each of the exons 6 to 8. These findings show that GPDH isozymes in C. chinensis are produced by the alternative processing of 3' exons. The occurrence of the three transcripts was proven by RT-PCR using synthetic oligonucleotides complementary to the predicted unique 3' regions. Compared to the D. melanogaster GPDH isozymes, GPDH-1, -2, and -3, C. chinensis GPDH showed 83.6%, 83%, and 84% identities, respectively.
Mol Cells 2001 Jun 30
PMID:Cloning and sequence analysis of Gpdh in Callosobruchus chinensis (Coleoptera: Bruchidae). 1145 33


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