Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Michaelis-Menten kinetics are observed in studies of highly purified bovine adrenal glucose-6-phosphate dehydrogenase at pH8.0 in 0.1 M bicine. The Km for NADP+ is 3.8 muM and for glucose-6-phosphate, 61 muM. At pH 6.9 Km for NADP+ increases to 6.5 muM. The enzyme is inhibited by NADPH both at pH 6.8 and at 8.0 with a Kip of 2.36 muM at pH 8.0. Inhibition is competitive with respect to both substrates implying that addition of substrates is random ordered. The data are also interpreted in terms of "reducing charge", the mole fraction of coenzyme in the reduced form. This appears to be the major mechanism for regulation of the pentose shunt. D-glucose, oxidized by the enzyme at a very slow rate, is also a competitive inhibitor for the natural substrate with a Ki of 0.29 M. Phosphate is a competitive inhibitor for glucose-6-phosphate oxidation but both phosphate and sulfate accelerate glucose oxidation suggesting a common binding site for the two anions and the phosphate of the natural substrate. While binding of ACTH to our enzyme preparations has been observed, we have not been able, in spite of repeated attempts, to demonstrate augmentation of the activity of the enzyme by the addition of ACTH.
 ...
PMID:Kinetics and control of bovine adrenal glucose-6-phosphate dehydrogenase. 0 67

1. Pyridoxal 5'-phosphate inhibits glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides reversibly which Ki equals 0.04-0.06 mM. 2. This inhibition is competitive with respect to glucose 6-phosphate and non-competitive with respect to NADP+ or NAD+. Interaction between enzyme and excess pyridoxal 5'-phosphate follows pseudo-first-order kinetics and indicates that one molecule of inhibitor reacts with each active unit of enzyme. 3. Substrate and coenzyme protect the enzyme from inhibition by pyridoxal 5'-phosphate. Dissociation constants for NADP+ and glucose 6-phosphate were determined from their effects on the kinetics of enzyme--inhibitor interaction. 4. Reaction of the enzyme with pyridoxal 5'-phosphate produces a typical Schiff-base absorbance peak at 430 nm. Subsequent reduction with sodium borohydride leads to spectral changes characteristic for the formation of a secondary amine. 5. The irreversibly inactivated enzyme thus produced contains two moles of inhibitor per mole of enzyme (two subunits per mole). After protein hydrolysis, N-6-pyridoxyllysine can be identified by paper chromatography. 6. The enzyme is inhibited irreversibly by 1-fluoro-2,4-dinitrobenzene, even in the presence of excess 2-mercaptoethanol. At least one dinitrophenyl group is bound per active unit of enzyme; 4 to 5 moles of dinitrophenyl group are bound per mole of enzyme. NADP+ AND GLUCOSE 6-PHOSPHATE PROTECT AGAINST INHIBITION BY 1-FLUORO-2,4-DINITROBENZENE. The absorption spectrum of dinitrophenyl-enzyme corresponds to that for dinitrophenylated amino groups. 7. These studies indicate that there is an essential lysine at the active site of the enzyme. It is suggested that the function of this lysine is to bind glucose 6-phosphate. 8. It is proposed that a group of "active lysine" proteins may exist (in analogy with the "active serine" enzymes), which share a common structural feature at their substrate-binding site and to which pyridoxal 5'-phosphate binds specifically.
 ...
PMID:Evidence for an essential lysine in glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides. 23 86

Acetaminophen, p-aminophenol, and oxyphenbutazone interfere with the glucose oxidase/peroxidase method for glucose. Structurally related compounds that lack a free phenolic hydroxyl group (acetanilide, aniline, and phenylbutazone) do not interfere. During the analytical procedure acetaminophen is consumed. One mole of acetaminophen leads to an apparent loss of four moles of glucose. The hexokinase/glucose-6-phosphate dehydrogenase method (Boehringer Hexokinase method) is not affected by these substances.
 ...
PMID:Interference by acetaminophen in the glucose oxidase-peroxidase method for blood glucose determination. 97 21

A nonradioactive multiwell spectrophotometric assay for the interferon-induced enzyme 2',5'-oligoadenylate synthetase measuring the inorganic pyrophosphate produced during oligoadenylate synthesis has been developed. A coupled enzymatic reaction results in a mole to mole formation of NADPH compared to the inorganic pyrophosphate through the use of the three enzymes UDP-Glc pyrophosphorylase (EC2.7.7.9), phosphoglucomutase (EC5.4.2.2), and glucose-6-phosphate dehydrogenase (EC1.1.1.49). The assay is at least as sensitive for measurements of 2',5'-oligoadenylate synthetase activity as the conventional assays using radioactive nucleotides as substrates. Even higher sensitivity of the assay can be obtained by taking advantage of the strong fluorescence of NADPH.
 ...
PMID:Spectrophotometric pyrophosphate assay of 2',5'-oligoadenylate synthetase. 133 38

Fatty acid-binding protein (FABP) was isolated, purified, and characterized from developing human fetal lung cytosol by gel filtration and ion-exchange chromatography. FABP exists in three immunochemically identical forms, DE-I, DE-II, and DE-III, having Mr 15,200 +/- 200 each and isoelectric pH 7.8, 6.9, and 5.4, respectively. DE-I is almost lipid-free, DE-II binds mainly long-chain unsaturated fatty acids, and DE-III is an arachidonic acid carrier. One mole of DE-II and DE-III each binds 1 mol of fatty acids noncovalently. Concentrations of all these FABPs increase gradually from early gestation to term. Defatted lung FABP reverses the inhibitory effect of palmitoyl coenzyme A (CoA) (PAL-CoA) on lung glucose-6-phosphate dehydrogenase (G6PD), a key enzyme of the hexose monophosphate (HMP) shunt pathway. This protein when added alone activates the enzyme, suggesting that the original submaximal activity is probably due to the presence of endogenous long-chain fatty acyl CoA esters in the cytosols. As FABP is present in relatively high concentration in most mammalian cells, the potent inhibitory effects of long-chain acyl CoA esters on the HMP shunt pathway in vitro are not seen in intact cells.
 ...
PMID:Purification and characterization of fatty acid-binding proteins from human fetal lung. 276 6

Human erythrocyte glucose-6-phosphate dehydrogenase contains a reactive lysyl residue, which can be labelled with pyridoxal 5'-phosphate. The binding of one mole of pyridoxal 5'-phosphate per mole of enzyme subunit produces substantial inactivation. The substrate glucose-6-phosphate prevents the loss of activity, suggesting that the reaction site is close to the substrate-binding site. A tryptic peptide containing the pyridoxal-5'-phosphate-binding lysyl residue has been isolated and characterised. The reactive lysyl residue has been identified in the glucose-6-phosphate dehydrogenase amino acid sequence. Comparison with glucose-6-phosphate dehydrogenase from other sources shows a high homology with a peptide containing a reactive lysyl residue, isolated from the enzyme from Saccharomyces cerevisiae; glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides also contains a region highly homologous with the sequence around the reactive lysyl residue in the human enzyme. The results of this communication provide the first direct evidence for the association of an essential catalytic function with a specific region of the molecule of human erythrocyte glucose-6-phosphate dehydrogenase.
 ...
PMID:Human erythrocyte glucose-6-phosphate dehydrogenase. Identification of a reactive lysyl residue labelled with pyridoxal 5'-phosphate. 312 64

Transient ATP synthesized by preparations enriched with plasmatic membranes of particles from the human placenta in the presence of insulin (4 micrograms/ml) and epidermal growth factor (1 microgram/ml) within 1 min after the addition of hormones at 30 degrees C, was isolated by means of chromatography on Dowex 1 X 8. ATP was synthesized in a medium containing Tris-HCl buffer, pH 7.5, ADP, Mg2+, and Pi during NADH-dependent oxidation in the presence of cytochrome C and oxygen. The amount of ATP was 10(-9) mole/mg protein/min. Quantitative assessment of ATP in lyophilized product was carried out by means of fluorimetry (excitation wavelength--360 nm; emission wavelength--460 nm) of NADH formed during coupled enzymatic reactions involving hexokinase and glucose-6-phosphate dehydrogenase. A possible biological role of peptide growth factor-stimulated formation of transient ATP in plasmatic membranes is discussed.
 ...
PMID:[ATP generation by the plasma membranes of human placental cells as affected by insulin and epidermal growth factor]. 354 74

CDKN2A is regarded as a major melanoma susceptibility gene. A 19 bp deletion has been detected within Dutch families with familial atypical multiple mole-melanoma syndrome. Genetic analysis revealed two individuals with germline deletions in both copies of CDKN2A. One of them did not develop atypical naevi or melanoma, but died of adenocarcinoma at the age of 54 years. This report describes the results of the investigation of the second p16-null individual, who was also found to have glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and who has developed many atypical naevi and seven melanomas. Using electron microscopic techniques, striking alterations in melanosomal structures and deviations in their sulphur, iron and calcium composition indicating a strong preference for phaeomelanogenesis and increased oxidative stress were found in the naevus cells of the patient. Using an in vitro model, we demonstrated that leaking melanin precursors may strongly enhance oxidative DNA damage through iron release from ferritin. We conclude that the homozygous p16 deletion is not sufficient for the development of a dysplastic naevus phenotype and melanoma. However, when an additional modifying factor, such as G-6-PD deficiency, increases the level of oxidative DNA damage in melanin-producing cells, the risk of developing atypical naevi and their malignant transformation may increase significantly.
 ...
PMID:Homozygous germline mutation of CDKN2A/p16 and glucose-6-phosphate dehydrogenase deficiency in a multiple melanoma case. 1269 Mar 1

The influence of low temperature on soybean (Glycine max [L.] Merr. cv. Wells) energy transduction via mitochondrial respiration and dehydrogenases was investigated in this study during imbibition and germination. Mitochondria were isolated from embryonic axes of seeds treated at 10 and 23 C (control) by submergence in H(2)O for 6 hours and maintenance for an additional 42 hours in a moist environment. Arrhenius plots of initial respiration rates revealed that those from cold-treated axes had respiratory control (RC) ratios of near 1.0 above an inflection in the plot at 8 C. Arrhenius plots of control axes mitochondrial respiration showed RC ratios of 2.8 above and 5.0 below an inflection temperature of 12.5 C. Energies of activation for mitochondrial respiration between 20 and 30 C for the cold and control treatments were 7.8 and 15.6 kcal/mole, respectively. These data indicate possible differences in mitochondrial membranes, degree of mitochondrial integrity, and mitochondrial enzyme complement between the two treatments.Glutamate dehydrogenase (GDH), malate dehydrogenase (MDH), alcohol dehydrogenase (ADH), glucose-6-phosphate dehydrogenase (G6P-DH), and NADP-isocitrate dehydrogenase (NADP-ICDH) were assayed from whole seeds and axes (after germination) during the 48 hours of temperature treatments. Activity of these dehydrogenases decreased during the first 6 hours with the exception of MDH. After germination at 23 C (48 hours) all five dehydrogenases increased in activity. Arrhenius plots of cotyledon dehydrogenase activities indicated that one inflection temperature between 6 and 18 C was present for each enzyme assayed. Differences were seen in Arrhenius plots of axes dehydrogenase activities with the two temperature treatments in the cases of GDH and MDH from mitochondrial pellets and with differences in enzyme extraction media. These data suggest that the temperature treatments yield differences in mitochondrial enzyme complement. There were no detectable inflection temperatures for the activities of G6P-DH and ADH extracted from axes. Arrhenius plots of NADP-ICDH activity indicated extreme cold sensitivity. The slopes of the plots for axes NADP-ICDH were very similar to those for mitochondrial respiration (23 C treatment) suggesting that this enzyme may limit mitochondrial respiration at low temperature in soybean tissues grown at moderate temperatures.
 ...
PMID:Low Temperature Effects on Soybean (Glycine max [L.] Merr. cv. Wells) Mitochondrial Respiration and Several Dehydrogenases during Imbibition and Germination. 1666 Jan 71