Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Glycerol”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources
PubMed1982

The mechanism of in sutu reactivation of glycerol-inactivated coenzyme B12-dependent enzymes, glycerol dehydratase and diol dehydratase.

In the previous paper (S. Honda, T. Toraya, and S. Fukui, J. Bacteriol., 143, 1458-1465 (1980)), we reported that the glycerol-inactivated holoenzymes of adenosylcobalamin-dependent glycerol dehydratase and diol dehydratase are rapidly and continually reactivated in toluene-treated cells (in situ) by adenosine 5'-triphosphate (ATP) and divalent metal ions in the presence of free adenosylcobalamin. To elucidate the mechanism of this in situ reactivation, the nature of the binding of various irreversible cobalamin inhibitors to the dehydratases in situ was investigated. In the presence of ATP and Mn2+, enzyme-bound hydroxocobalamin, cyanocobalamin and methylcobalamin were rapidly displaced by added adenosylcobalamin. Without ATP and Mn2+, such displacement did not take place. In contrast, enzyme-bound adeninylbutylcobalamin and adenosylethylcobalamin were essentially not displaceable by the free coenzyme even in the presence of ATP and Mn2+. Inosylcobalamin was a very weak inhibitor irrespective of the presence of ATP and Mn2+. These results indicate that the relative affinity of the enzymes in situ for the cobalamins with simple Co beta ligands was markedly lowered in the presence of ATP and Mn2+, whereas that for the cobalamins with adenine-containing ligands was not. When the glycerol-inactivated holoenzymes in situ were dialyzed against a buffer containing ATP and Mg2+, the inactivated coenzyme moiety dissociated from the enzymes leaving apoproteins. Kinetic evidence was also obtained with the dehydratases in situ that continual displacement of the inactivated coenzyme moiety by adenosylcobalamin takes place during the glycerol dehydration reaction in the presence of ATP and Mn2+. Since the adenosyl group of the bound coenzyme is irreversibly removed from the cobalamin moiety during inactivation by glycerol, all of these data constitute clear evidence that the inactivated holo-dehydratases are reactivated in situ in the presence of ATP and Mn2+ by displacement of the modified coenzyme moiety by free intact adenosylcobalamin (i.e. selective B12-exchange mechanism).

Adenosine Triphosphate↗
PubMed1998

An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity.

2-Arachidonoyl-glycerol (2-Ara-GI) has been isolated from various tissues and identified as an endogenous ligand for both cannabinoid receptors, CB1 and CB2. Here we report that in spleen, as in brain and gut, 2-Ara-GI is accompanied by several 2-acyl-glycerol esters, two major ones being 2-linoleoyl-glycerol (2-Lino-Gl) and 2-palmitoyl-glycerol (2-Palm-Gl). These two esters do not bind to the cannabinoid receptors, nor do they inhibit adenylyl cyclase via either CB1 or CB2; however, they significantly potentiate the apparent binding of 2-Ara-Gl and its apparent capacity to inhibit adenylyl cyclase. Together these esters also significantly potentiate 2-Ara-Gl inhibition of motor behavior, immobility on a ring, analgesia on a hot plate and hypothermia caused by 2-Ara-Gl in mice. 2-Lino-Gl, but not 2-Palm-GI, significantly inhibits the inactivation of 2-Ara-Gl by neuronal and basophilic cells. These data indicate that the biological activity of 2-Ara-Gl can be increased by related, endogenous 2-acyl-glycerols, which alone show no significant activity in any of the tests employed. This effect ('entourage effect') may represent a novel route for molecular regulation of endogenous cannabinoid activity.

Adenylyl Cyclase Inhibitors↗
PubMed1999

sn-glycerol-1-phosphate-forming activities in Archaea: separation of archaeal phospholipid biosynthesis and glycerol catabolism by glycerophosphate enantiomers.

In Methanobacterium thermoautotrophicum, sn-glycerol-1-phosphate (G-1-P) dehydrogenase is responsible for the formation of the Archaea-specific backbone of phospholipids, G-1-P, from dihydroxyacetonephosphate (DHAP). The possible G-1-P-forming activities were surveyed in cell-free extracts of six species of Archaea. All the archaeal cell-free homogenates tested revealed the ability to form G-1-P from DHAP. In addition, activities of G-3-P-forming glycerol kinase and G-3-P dehydrogenase were also detected in four heterotrophic archaea, while glycerol kinase activity was not detected in two autotrophic methanogens. These results show that G-1-P is produced from DHAP by G-1-P dehydrogenase in a wide variety of archaea while exogenous glycerol is catabolized via G-3-P.

Dihydroxyacetone Phosphate↗
PubMed2000

Cloning and characterization of a putative human glycerol 3-phosphate permease gene (SLC37A1 or G3PP) on 21q22.3: mutation analysis in two candidate phenotypes, DFNB10 and a glycerol kinase deficiency.

Using multiple exons trapped from human chromosome 21 (HC21)-specific cosmids with homology to a putative Arabidopsis thaliana glycerol 3-phosphate permease, we have determined the full-length cDNA sequence of a novel HC21 gene encoding a putative sugar-phosphate transporter (HGMW-approved symbol SLC37A1, aka G3PP). The predicted protein has 12 putative transmembrane domains and is also highly homologous to bacterial glpT proteins. The transcript was precisely mapped to 21q22.3 between D21S49 and D21S113. Comparison of the SLC37A1 cDNA to genomic sequence revealed that the gene encompasses 82 kb, and it is split into 19 coding exons and 7 untranslated exons, which are alternatively spliced in a complex and tissue-specific manner. Glycerol 3-phosphate (G3P) is produced by glycerol kinase (GK) and is found in several biochemical pathways in different cellular compartments, such as the glycerol phosphate shuttle and glycerophospholipid synthesis. Thus SLC37A1 mutations may cause a phenotype similar to GK deficiency. Mutational analyses of SLC37A1 in seven patients with no mutations in the GK gene and low GK activity revealed only nonpathogenetic sequence variants, excluding SLC37A1 as the gene for the phenotype in these patients. SLC37A1 maps in the refined critical region of the autosomal recessive deafness locus, DFNB10, on 21q22.3. Mutation analyses also excluded SLC37A1 as the gene for DFNB10.

Amino Acid Sequence↗
PubMed1992

Effect of the chirality of the glycerol backbone on the bilayer and nonbilayer phase transitions in the diastereomers of di-dodecyl-beta-D-glucopyranosyl glycerol.

We have studied the physical properties of aqueous dispersions of 1,2-sn- and 2,3-sn-didodecyl-beta-D-glucopyranosyl glycerols, as well as their diastereomeric mixture, using differential scanning calorimetry and low angle x-ray diffraction. Upon heating, both the chiral lipids and the diastereomeric mixture exhibit characteristically energetic L beta/L alpha phase transitions at 31.7-32.8 degrees C and two or three weakly energetic thermal events between 49 degrees C and 89 degrees C. In the diastereomeric mixture and the 1,2-sn glycerol derivative, these higher temperature endotherms correspond to the formation of, and interconversions between, several nonlamellar structures and have been assigned to L alpha/QIIa, QIIa/QIIb, and QIIb/HII phase transitions, respectively. The cubic phases QIIa and QIIb, whose cell lattice parameters are strongly temperature dependent, can be identified as belonging to space groups Ia3d and Pn3m/Pn3, respectively. In the equivalent 2,3-sn glucolipid, the QIIa phase is not observed and only two transitions are seen at 49 degrees C and 77 degrees C, which are identified as L alpha/QIIb and QIIb/HII phase transitions, respectively. These phase transitions temperatures are some 10 degrees C lower than those of the corresponding phase transitions observed in the diastereomeric mixture and the 1,2-sn glycerol derivative. On cooling, all three lipids exhibit a minor higher temperature exothermic event, which can be assigned to a HII/QIIb phase transition. An exothermic L alpha/L beta phase transition is observed at 30-31 degrees C. A shoulder is sometimes discernible on the high temperature side of the L alpha/L beta event, which may originate from a QIIb/L alpha phase transition prior to the freezing of the hydrocarbon chains. None of the lipids show evidence of a QIIa phase on cooling. No additional exothermic transitions are observed on further cooling to -3 degrees C. However, after nucleation at 0 degrees C followed by a short period of annealing at 22 degrees C, the 1,2-sn glucolipid forms an Lc phase that converts to an L alpha phase at 39.5 degrees C on heating. Neither the diastereomeric mixture nor the 2,3-sn glycerol derivative shows such behavior even after extended periods of annealing. Our results suggest that the differences in the phase behavior of these glycolipid isomers may not be attributable to headgroup size per se, but rather to differences in the stereochemistry of the lipid polar/apolar interfacial region, which consequently effects hydrogen-bonding, hydration, and the hydrophilic/hydrophobic balance.

Biophysical Phenomena↗
PubMed1981

Mechanism of protein stabilization by glycerol: preferential hydration in glycerol-water mixtures.

A densimetric investigation of the interactions between solvent components in glycerol-water mixtures (between 10 and 40 vol % glycerol) and seven proteins have been carried out in the acid pH region. All the proteins were found to be preferentially hydrated at all conditions used, i.e., addition of the proteins to the mixed solvent results in an increase in the chemical potential of glycerol. It is considered that this thermodynamically unfavorable interaction should tend to minimize the surface of contact between proteins and glycerol and in this way stabilize the native structure of globular proteins.

Densitometry↗
PubMed1972

Activity of fluoro and deoxy analogues of glycerol as substrates and inhibitors of glycerol kinase.

Analogues of glycerol in which each of the three hydroxy groups is successively replaced by fluorine or hydrogen have been examined as substrates or inhibitors of glycerol kinase (Candida mycoderma) to assess the ability of fluorine to mimic a substrate hydroxy group in enzyme-analogue interactions. The four diols resulting from replacement of the hydroxy groups at C-1 or C-2 of sn-glycerol by fluorine or hydrogen are weak substrates. Similar substitution of the C-3 hydroxy group gives compounds which act as competitive inhibitors of glycerol or dihydroxyacetone phosphorylation but show no activity as substrates. Comparison of the steady-state kinetic parameters of the corresponding analogues shows that replacement of a hydroxy group by either fluorine or hydrogen leads to compounds with similar activity in this system. A convenient synthesis of (+)-propane-1,2-diol is described.

Candida↗
PubMed2004

High osmolarity glycerol (HOG) pathway-induced phosphorylation and activation of 6-phosphofructo-2-kinase are essential for glycerol accumulation and yeast cell proliferation under hyperosmotic stress.

In response to changes in the environment, yeast cells coordinate intracellular activities to optimize survival and proliferation. The transductions of diverse extracellular stimuli are exerted through multiple mitogen-activated protein kinase (MAPK) cascades. The high osmolarity glycerol (HOG) MAPK pathway is activated by increased environmental osmolarity and results in a rise of the cellular glycerol concentration to adapt the intracellular osmotic pressure. We studied the importance of the short time regulation of glycolysis under hyperosmotic stress for the survival and proliferation of yeast cells. A stimulation of the HOG-MAPK pathway by increasing the medium osmolarity through addition of salt or glucose to cultivated yeast leads to an activation of 6-phosphofructo-2-kinase (PFK2), which is accompanied by a complex phosphorylation pattern of the enzyme. An increase in medium osmolarity with 5% NaCl activates PFK2 3-fold over the initial value. This change in the activity is the result of a 4-fold phosphorylation of the enzyme mediated by protein kinases from the HOG-MAPK pathway. In the case of hyperosmolar glucose a 5-fold PFK2 activation was achieved by a single phosphorylation with protein kinase A near the carboxyl terminus of the protein on Ser(644) and an additional 5-fold phosphorylation within the same amino-terminal fragment as in the presence of salt. The effect of hyperosmolar glucose is the result of an activation of the Ras-cAMP pathway together with the HOG-MAPK pathway. The activation of PFK2 leads to an activation of the upper part of glycolysis, which is a precondition for glycerol accumulation. Yeast cells containing PFK2 accumulate three times more glycerol than cells lacking PFK2, which are not able to grow under hypertonic stress.

Blotting, Western↗
PubMed1983

Comparison of post-thaw sperm motility after freezing in liquid nitrogen with protective media of either glycerol or glycerol-egg-yolk-citrate.

Thirty semen samples with a mean prefreezing motility of 70.4% were frozen for 1 month in liquid nitrogen by means of a modified Barkay's method and with either glycerol or glycerol-egg-yolk-citrate (GEYC) as protective media. The post-thaw motility was found to be 37.9% and 30.7% and cryosurvival rate (CSR) was 54.6% and 44.4%, respectively--the difference being significant (P less than 0.05). When samples achieving at least 40% of post-thaw-motility (PTM) in either medium were selected, the mean prefreezing motility increased to a 71.6%, and the PTM and the average CSR were 44.1% and 62.2% and 35.5% and 50%, respectively, when either glycerol or GEYC was used. It appears that glycerol alone is superior to a mixture of GEYC for cryo-preservation of sperm if the technique mentioned above is used and PTM is a criterion for sperm quality.

Citrates↗
PubMed1977

Regulation of selectivity of CDPcholine: 1,2-diacyl-sn-glycerol cholinephosphotransferase in rat liver microsomes towards different molecular species of 1,2-diacyl-sn-glycerols.

The suitability of monoenoic, dienoic, tetraenoic, and hexaenoic molecular species of 1,2-diacyl-sn-glycerols as substrates for the CDPcholine: 1,2-diacyl-sn-glycerol cholinephosphotransferase (EC 2.7.8.2) was studied in rat liver microsomes. No statistically significant difference in the rates of phosphatidylcholine synthesis with the various diacylglycerols was found at 0.40 mM, although a moderate discrimination against hexaenoic species relative to monoenoic and dienoic species was observed at 0.25 mM. The addition of palmitoyl-CoA (7.5 micron) significantly enhanced cholinephosphotransferase activity when tetraenoic diacylglycerols were added at 0.25 or 0.40 mM. CDPethanolamine at 24.4 micron was found to inhibit the rates of phophatidylcholine biosynthesis by 54 and 39% with hexaenoic and monoenoic 1,2-diacyl-sn-glycerols, respectively, whereas no significant effects were observed in the case of dienoic and tetraenoic species. These latter findings may partially explain why 1-saturated 2-docosahexaenoyl diacylglycerols are used to a greater extent for phosphatidylethanolamine than for phosphatidylcholine synthesis in rat liver in vivo. The present results also suggest that the selectivity of the cholinephosphotransferase for certain molecular species of 1,2-diacyl-sn-glycerols is a function of diacylglycerol concentration and may be mediated under physiological conditions by substrates for enzymes which compete for common diacylglycerol precursors.

Animals↗
PubMed1987

Glycerol metabolism in higher plants: glycerol kinase.

Glycerol kinase activity was identified in extracts of higher plant seeds and seedlings, and was partially purified and characterized from cucumber radicle tissue. The enzyme was localized in the post-mitochondrial supernatant of the cell, and catalyzed the formation of glycerol-3-phosphate. The pH optiumum was 9.0. ATP, CTP, GTP or UTP could be used as the phosphoryl group donor. The Km for glycerol was 55 microM and Km values for the nucleoside triphosphates were 145-620 microM. The Vmax for the reaction was 40-78 pmol product per min. Kinetic data indicate that the enzyme has a sequential mechanism.

Glycerol↗
PubMed1998

Clinical heterogeneity and novel mutations in the glycerol kinase gene in three families with isolated glycerol kinase deficiency.

Isolated glycerol kinase deficiency (GKD) is an X linked recessive disorder. The clinical and biochemical picture may vary from a childhood metabolic crisis to asymptomatic adult "pseudohypertriglyceridaemia", the result of hyperglycerolaemia. We performed glycerol kinase (GK) gene analysis to study the molecular heterogeneity and genotype-phenotype correlation in eight males from three families with isolated GKD. All patients had hyperglycerolaemia and glyceroluria. Four patients from two families were essentially free of symptoms. Three patients had gastrointestinal symptoms with ketoacidosis or hypoglycaemia or both. One patient had recurrent convulsions as the only acute sign, without evidence that it was correlated with a catabolic state. Fasting tests in two symptomatic patients of family 1 showed hyperketotic states, together with a tendency to hypoglycaemia. The diagnosis was confirmed by a defective 14C-glycerol incorporation into trichloroacetic acid precipitable macromolecules in intact skin fibroblasts. Mutation screening of the GK gene was performed by amplification and direct sequencing of exons using PCR. Three novel mutations were identified: (1) a deletion starting downstream of exon 9, extending to the 3' end of the gene; (2) a nonsense mutation R413X caused by a C1351T transition; and (3) a missense mutation W503R caused by a T1651C transition. In addition, we found differences from the reported sequence: (1) exon 9 actually consists of two exons, which consequently will change the number of GK gene exons from 19 to 20 exons, and (2) nucleotide differences in exon 19. So far, no genotype-phenotype correlation can be established in these GKD families.

Amino Acid Sequence↗
PubMed1977

Study on the mechanism of action of adenosylcobalamin-dependent glycerol dehydratase from Aerobacter aerogenes. I. Role of structural components of adenosylcobalamin the formation of the active site of glycerol dehydratase.

A new method of partial chemical synthesis of adenosylcobalamin (Co alpha-[alpha-5,6-diemethylbenzimidazolyl)]-Co beta-adenosylcobamide, AdoCbl) analogs has been developed. A series of derivatives of AdoCbl modified in the nucleoside and nucleotide ligands and corrin macrocycle have been obtained. The interaction of AdoCl analogs with glycerol dehydratase (EC 4.2.1.30) from Aerobacter aerogenes has been investigated. It has been shown that the nucleoside ligand of AdoCbl provides no essential contribution to the binding of apoenzyme but the preservation of the exact structure of the 1-N and 2-C positions of adenine appears essential for the catalysis. The coordination bond between the Co and nucleotide ligand of AdoCl does not play a decisive role in glycerol dehydratase activity. To form the active site of the glycerol dehydrates, the nucleotide in the AdoCbl structure is essential since nucleotide elimination results in a 100-fold increase of Ki for the corresponding analog. In the binding of AdoCbl with apoenzyme, the main role belongs to the corrin macrocycle, in which the e-propionamide group is significant for binding with apoenzyme, but presumably not essential for catalysis.

Adenine Nucleotides↗
PubMed1992

Inhibition of glycerol-3-phosphate acyltransferase by analogs of glycerol-3-phosphate.

Analogs of glycerol-3-phosphate were tested as substrates or inhibitors of the glycerol-3-phosphate acyltransferases of mitochondria and microsomes. (rac)-3,4-Dihydroxybutyl-1-phosphonate, (rac)-glyceraldehyde 3-phosphate, (rac)-3-hydroxy-4-oxobutyl-1-phosphonate, (1S,3S)-1,3,4-trihydroxybutyl-1-phosphonate, and (1R,3S)-1,3,4 trihydroxybutyl-1-phosphonate were competitive inhibitors of both mitochondrial and microsomal sn-glycerol-3-phosphate acyltransferase activity. An isosteric analog of dihydroxyacetone phosphate, 4-hydroxy-3-oxobutyl-1-phosphonate, was a much stronger competitive inhibitor of the microsomal than the mitochondrial enzyme. Phenethyl alcohol was a noncompetitive inhibitor of both the microsomal and the mitochondrial acyltransferases. The product of the mitochondrial acyltransferase reaction with (rac)-3,4-dihydroxybutyl-1- phosphonate was almost exclusively (rac)-4-palmitoyloxy-3-hydroxybutyl-1-phosphonate. The microsomal acylation reaction generated both the monoacyl product and (S)-3,4-dipalmitoyloxybutyl-1-phosphonate. The apparent Km for (S)-3,4-dihydroxybutyl-1-phosphonate was 2.50 and 1.38 mM for the mitochondrial and microsomal enzymes, respectively.

Acylation↗
PubMed1980

The use of an immobilized glycerol dehydrogenase nylon-tube reactor in the determination of glycerol.

A continuous-flow system is described that utilizes an immobilized glycerol dehydrogenase nylon-tube reactor integrated into the flow system of a Technicon AutoAnalyzer II for the routine estimation of glycerol in serum and various beverages. Results are compared with determinations made by the solution method that uses the three enzymes glycerokinase, pyruvate kinase and lactate dehydrogenase. These routine trials give reliable and reproducible results with high precision and economy. The glycerol dehydrogenase reactor is stable during intermittent or continuous use for a least 3500 tests. Stored at 4 degrees C when not in use, the reactor is quite stable for several months.

Autoanalysis↗
PubMed1981

Regulation of hepatic fatty acid metabolism. The activities of mitochondrial and microsomal acyl-CoA:sn-glycerol 3-phosphate O-acyltransferase and the concentrations of malonyl-CoA, non-esterified and esterified carnitine, glycerol 3-phosphate, ketone bodies and long-chain acyl-CoA esters in livers of fed or starved pregnant, lactating and weaned rats.

1. The concentrations of malonyl-CoA, glycerol 3-phosphate, non-esterified carnitine, acid-soluble and acid-insoluble acylcarnitines, acetoacetate, 3-hydroxybutyrate and acid-insoluble acyl-CoA were measured in rapidly-frozen liver samples from fed or starved (24h) virgin, pregnant (19-20 days), lactating (2, 10-12 and 18-20 days) and weaned (for 24h, on 10th day of lactation) rats. The activities of total and N-ethylmaleimide-sensitive and -insensitive glycerophosphate acyltransferase (acyl-CoA:sn-glycerol 3-phosphate O-acyltransferase; EC 2.3.1.15) were also measured. 2. The concentration of malonyl-CoA was significantly higher in liver of fed pregnant, mid- and late-lactating rats than in liver of fed virgin rats. After starvation for 24h hepatic malonyl-CoA concentrations were higher in mid-lactating rats and lower in pregnant and weaned rats than in virgin animals. 3. After starvation for 24h the hepatic concentrations of glycerol 3-phosphate, ketone bodies, acid-soluble acylcarnitines and the value for the [3-hydroxybutyrate]/[acetoacetate] ratio were all highest in pregnant rats, intermediate in virgin, 2-day lactating and weaned animals and lowest in mid- and late-lactating rats. The concentrations of acid-insoluble acylcarnitines also increased most in pregnant rats, after starvation. The concentration of acid-insoluble acyl-CoA increased equally after starvation in virgin and pregnant animals but did not increase significantly in all other animals studied. 4. The total concentration of carnitine was similar in livers of fed virgin, pregnant and 2-day lactating animals but fell markedly by the 10th day of lactation and remained low in late-lactating animals. The concentration of non-esterified carnitine followed the same pattern. After starvation for 24h the hepatic concentration of non-esterified carnitine decreased significantly in virgin, pregnant and 2-day lactating animals, but remained unchanged in mid- and late-lactating or weaned animals. 5. The activities of N-ethylmaleimide-sensitive and -insensitive glycerophosphate acyltransferase both increased significantly in livers of mid-lactating animals. After starvation for 24h the activity of the N-ethylmaleimide-insensitive O-acyltransferase decreased in livers of virgin, pregnant and mid-lactating animals, whereas the activity of the N-ethylmaleimide-sensitive O-acyltransferase was unchanged in virgin animals but decreased markedly in livers of pregnant and lactating rats. 6. The results are discussed in relation to the importance of different metabolic parameters in the regulation of long-chain acyl-CoA metabolism in the liver.

Acyl Coenzyme A↗
PubMedDate not supplied

Removal of HBSAg from blood in vitro. I. Effects of washing alone, glycerol addition and removal, and glycerolization, freezing, and washing.

Red blood cells from HBSAg-positive blood were washed in the Fenwal Elutramatic, Haemonetics Processor 15, or the IBM Blood Processor with sodium chloride solutions, or in the Huggins Cytoglomerator with sugar solutions. The Fenwal Elutramatic and IBM Blood Processor were the most efficient washing systems, the Haemonetics Processor 15 was less efficient, and the Huggins Cytoglomerator was the least efficient in removing the HBSAg. Washing to remove the HBSAg from red blood cells containing 40 per cent W/V glycerol in an ionic medium was more efficient than washing HBSAg from liquid-stored red blood cells or red blood cells containing 20 per cent W/V glycerol. The original and modified dilution/agglomeration wash cycles used in the Huggins Cytoglomerator were not able to remove the HBSAg from units of blood that were radioimmune assay (RIA) positive and counterelectrophoresis (CEP) negative. Freezing had no effect on the removal of the HBSAg in vitro, whereas the concentration of 40 per cent W/V glycerol in the red blood cells that were washed did. HBSAg was not found in the amorphous debris remaining in the polycarbonate disposable bowl used in the Haemonetics Processor 15 or in the microaggregates remaining in washed red blood cells.

Blood Preservation↗
PubMed2005

Targeted disruption of glycerol kinase gene in mice: expression analysis in liver shows alterations in network partners related to glycerol kinase activity.

Glycerol kinase deficiency (GKD) is an X-linked inborn error of metabolism with metabolic and neurological crises. Liver shows the highest level of glycerol kinase (GK) activity in humans and mice. Absence of genotype-phenotype correlations in patients with GKD indicates the involvement of modifier genes, including other network partners. To understand the molecular pathogenesis of GKD, we performed microarray analysis on liver mRNA from neonatal glycerol kinase (Gyk) knockout (KO) and wild-type (WT) mice. Unsupervised learning revealed that the overall gene expression profile of the KO mice was different from that of WT. Real-time PCR confirmed the differences for selected genes. Functional gene enrichment analysis was used to find 56 increased and 37 decreased gene functional categories. PathwayAssist analysis identified changes in gene expression levels of genes involved in organic acid metabolism indicating that GK was part of the same metabolic network which correlates well with the patients with GKD having metabolic acidemia during their episodic crises. Network component analysis (NCA) showed that transcription factors sterol regulatory element-binding protein (SREBP)-1c, carbohydrate response element-binding protein (ChREBP), hepatocyte nuclear factor-4 alpha (HNF-4alpha) and peroxisome proliferative-activated receptor-alpha (PPARalpha) had increased activity in the Gyk KO mice compared with WT mice, whereas SREBP-2 was less active in the Gyk KO mice. These studies show that Gyk deletion causes alterations in expression of genes in several regulatory networks and is the first time NCA has been used to expand on microarray data from a mouse KO model of a human disease.

Animals↗