Disease relevance of Dihydroxyacetone

• Here we report the 2.5-A crystal structure of the homodimeric Citrobacter freundii dihydroxyacetone kinase complex with an ATP analogue and dihydroxyacetone [1].
• DhaQ and DhaS form a stable complex that in the presence of Dha activates transcription of the Lactococcus lactis dha operon [2].
• Ultrasound identified an additional 3 cases of soleal vein thrombosis, but venography did not visualize these veins [3].
• Glycolaldehyde, glyceraldehyde, and dihydroxyacetone greatly enhanced the mutation rates in SOD-deficient E. coli [4].
• These results are consistent with a requirement for water at low relative humidity, which facilitates formation of free amine groups needed for the initial reaction with dihydroxyacetone, and with inhibition of the dehydration reactions by water through the law of mass action at high relative humidity [5].

High impact information on Dihydroxyacetone

• In cells of both pex14-1 and a PEX14 disruption mutant, peroxisomal membrane remnants were evident; these contained the H.polymorpha peroxisomal membrane protein Pex3p together with a small amount of the major peroxisomal matrix proteins alcohol oxidase, catalase and dihydroxyacetone synthase, the bulk of which resided in the cytosol [6].
• Phylogenetic analysis suggests that the PTS-dependent dihydroxyacetone kinases evolved from an ATP-dependent ancestor [7].
• Thus, TbAQPs represent mainly water/glycerol/dihydroxyacetone channels involved in osmoregulation and glycerol metabolism in T. brucei [8].
• We furthermore show that their substrate, dihydroxyacetone (DHA), is toxic to yeast cells and that the detoxification is dependent on functional DAK [9].
• We show here that dihydroxyacetone, a secretagogue that feeds into glycolysis below the putative oscillator phosphofructokinase, could cause a single initial peak in cytoplasmic free Ca2+ ([Ca2+]i) but did not by itself cause repeated oscillations in [Ca2+]i in mouse pancreatic beta-cells [10].

Chemical compound and disease context of Dihydroxyacetone

• Glycerol dehydrogenase (EC 1.1.1.6) and dihydroxyacetone kinase (EC 2.7.1.29) were purified from Citrobacter freundii [11].
• Acinetobacter sp. strain JC1 DSM 3803, a carboxydobacterium, grown on methanol was found to show dihydroxyacetone synthase, dihydroxyacetone kinase, and ribulose 1,5-bisphosphate carboxylase, but no hydroxypyruvate reductase and very low hexulose 6-phosphate synthase, activities [12].
• Earlier studies showed that the fatty liver, caused by feeding rats the Lieber-DeCarli alcohol diet for four weeks, was prevented if the diet was supplemented with dihydroxyacetone (22 g/l), pyruvate (22 g/l) and riboflavin (2.2 g/l) [13].
• Strain RG1(T) differed from Acetobacter aceti, the nearest member with a 16S rRNA gene sequence similarity of 98.2 %, and type strains of other Acetobacter species with regard to several characteristics of growth features in culture media, growth in nitrogen-free medium, production of gamma-pyrone from glucose and dihydroxyacetone from glycerol [14].
• Hence, the prevention of alcoholic fatty liver by the dietary supplementation with dihydroxyacetone and pyruvate may not be related to their capacity to serve as hydrogen acceptors and to oxidize NADH produced during ethanol metabolism [13].

Biological context of Dihydroxyacetone

• Inhibitors of gluconeogenesis from pyruvate had no effect on the ability of the hormone to stimulate the synthesis of [14C]glucose from dihydroxyacetone [15].
• Their nucleotide binding subunit, an eight-helix barrel of regular up-down topology, retains ADP as phosphorylation site for the double displacement of phosphate from a phospho-histidine of the PTS protein to dihydroxyacetone [7].
• The enzyme is specific for NADPH, but the sugar binding site will also accept 5-keto-D-fructose and dihydroxyacetone as substrates [16].
• In cells deleted for the function of Mpp1p the levels of various proteins involved in peroxisome biogenesis (peroxins) and function (enzymes) are reduced compared with wild type or, in the case of the matrix protein dihydroxyacetone synthase, fully absent [17].
• Cycloheximide did not stimulate gluconeogenesis from dihydroxyacetone, or phosphorylase in hepatocytes from starved rats, or glycogenolysis in hepatocytes from fed rats [18].

Anatomical context of Dihydroxyacetone

• In the present work we studied the effects of exogenous Mg-ATP in rat liver cells perifused with dihydroxyacetone to investigate simultaneously gluconeogenetic and glycolytic pathways [19].
• Mice were injected with peroxisomal membrane, and hybridoma lines were isolated that produced antibody against PMP 20, PMP 47, and dihydroxyacetone synthase [20].
• To investigate this, the effect of D-glyceraldehyde, dihydroxyacetone, D-mannoheptulose and glucose variations during arginine stimulation on the release of somatostatin and glucagon from the isolated pancreas of normal and streptozotocin diabetic dogs was studied [21].
• The differential effects of several specific inhibitors of intermediary metabolism, mannoheptulose, 2-deoxylucose, and iodoacetate, were studied with isolated perifused pancreatic islets stimulated with glucose, mannose, glyceraldehyde, dihydroxyacetone, or alpha-ketoisocaproate [22].
• Glycerol and dihydroxyacetone are metabolized by rabbit kidney-cortex tubules, isolated by collagenase treatment [23].

Associations of Dihydroxyacetone with other chemical compounds

• In cells from gasted rats, where lactate production is greatly reduced and the rate of glucose synthesis is elevated, glucagon did not stimulate gluconeogenesis from dihydroxyacetone [15].
• Atractyloside inhibited gluconeogenesis from dihydroxyacetone in hepatocytes from fasted rats and increased lactate synthesis [24].
• The regulation of pyruvate kinase in isolated hepatocytes from fasted rats was studied where the intracellular level of fructose 1,6-bisphosphate was elevated 5-fold by the addition of 5 mM dihydroxyacetone [25].
• A series of PLC experiments with phosphatidyl dihydroxyacetone and phosphatidyl 1,3-propanediol as model substrates supported this assignment [26].
• Several pathways were identified for catalysis of the isomerization of glyceraldehyde to give dihydroxyacetone [27].

Gene context of Dihydroxyacetone

• After cloning of the gene onto high-copy-number vectors, transaldolase B (D-sedoheptulose-7-phosphate:D-glyceraldehyde-3-phosphate dihydroxyacetone transferase; EC 2.2.1.2) was overexpressed up to 12.7 U mg of protein-1 compared with less than 0.1 U mg of protein-1 in wild-type homogenates [28].
• The level of Pex5p, the receptor involved in import of alcohol oxidase and dihydroxyacetone synthase into peroxisomes, was also reduced in both disruption strains compared to that in wild-type cells [29].
• A nitrogen-metabolic PTS phosphoryl transfer chain encoded within the rpoN and ptsP operons and a tri-domain regulatory PTS protein encoded within the dha (dihydroxyacetone catabolic) operon, probably serve regulatory roles exclusively [30].
• KATP channel inhibition mediated by dihydroxyacetone, which gives reducing equivalents directly to complex II of the electron transport system, was similar in Ad-Null-, Ad-UCP2- and Ad-UCP2+Ad-SHP-infected cells [31].
• [Katz, J., Golden, S. & Wals, P.A. (1976) Proc. Natl Acad. Sci. USA 73, 3433-3437] were the first to report that in hepatocytes isolated from fasted rats and incubated with either dihydroxyacetone, glucose or other sugars, glycogen synthesis was greatly accelerated by addition of amino acids [32].

Analytical, diagnostic and therapeutic context of Dihydroxyacetone

• A second covalent complex, approximately 20-24% of bound dihydroxyacetone [32P]phosphate, remains with the protein during acid denaturation and centrifugation [33].
• Medial tibial release included soleal and transverse fasciectomy, with periosteal cautery of the tibial insertions [34].
• Double immunodiffusion revealed that the antigenic sites of CO-DHs, RuBisCOs, and dihydroxyacetone synthases in all mycobacteria tested are identical with those of the Mycobacterium sp. strain JC1 enzymes [35].
• Orally fed pyruvate (pyr) and dihydroxyacetone (DHA) have been shown to decrease liver lipid accumulation in animal models [36].
• Alanine (10 mM), dihydroxyacetone (20 mM), or glutamine (10 mM) was then added to the reservoir, and perfusions continued for 60 min [37].

References