Aminolevulinic acid (ALA) is biosynthesized by the enzyme ALA synthase (ALAS). The ALA production has been studied using the overproducing ALAS from several bacteria in Escherchia coil, respectively. However, ALAS from eucaryote expressed in E. coli for producing ALA in the culture is not known. The extracellular ALA production and cell growth were investageted respectively using the recombinant E. coli overproducing Saccharomyces cerevisiae ALAS in shake-flask fermentations. The ALAS activity from the cell extract was assayed. The extracellular ALA was purified by the national-made large-dimension resins and confirmed by the capillary electrophoresis measurements. At 12h after induction at 37 degrees C, the extracellular ALA production was up to 162mg per liter LB culture at initial pH 6.5 with exogenous levulinate, succinate and and glycine at the concentration of 20 mmol/L respectively. The purity of ALA after purification is up to 90%.
5-Aminolevulinate Synthetase ; genetics ; metabolism ; Aminolevulinic Acid ; isolation & purification ; metabolism ; Cell Division ; drug effects ; Dose-Response Relationship, Drug ; Electrophoresis, Capillary ; Escherichia coli ; genetics ; growth & development ; metabolism ; Extracellular Space ; drug effects ; metabolism ; Glycine ; pharmacology ; Hydrogen-Ion Concentration ; Levulinic Acids ; pharmacology ; Recombinant Proteins ; metabolism ; Saccharomyces cerevisiae ; enzymology ; genetics ; Saccharomyces cerevisiae Proteins ; genetics ; metabolism ; Succinic Acid ; pharmacology

OBJECTIVEA series of 4-aryl substituted semicarbazones of levulinic acid (4-oxo pentanoic acid) was designed and synthesized to meet the structural requirements essential for anticonvulsant activity.

METHODSAll the compounds were evaluated for anticonvulsant activity. Anticonvulsant activity was determined after intraperitoneal (i.p.) administration to mice by maximal electroshock (MES) and subcutaneous metrazol (ScMet) induced seizure methods and minimal motor impairment was determined by rotorod test.

RESULTSA majority of the compounds exhibited significant anticonvulsant activity after intraperitoneal administration. In the present study 4-(4'-fluoro phenyl) levulinic acid semicarbazone emerged as the most active molecule, showing broad spectrum of activity with low neurotoxicity. Unsubstituted levulinic acid semicarbazone was found to be inactive in all the screens.

CONCLUSIONThe results obtained validate the hypothesis that presence of an aryl group near the semicarbazone moiety is essential for anticonvulsant activity. The results also indicate that the hydrophilic-hydrophobic site can accommodate hydrophilic groups.

Animals ; Anticonvulsants ; administration & dosage ; adverse effects ; analysis ; chemistry ; Drug Evaluation, Preclinical ; Injections, Intraperitoneal ; Levulinic Acids ; administration & dosage ; adverse effects ; analysis ; chemistry ; Mice ; Seizures ; drug therapy ; Semicarbazones ; administration & dosage ; adverse effects ; analysis ; chemistry ; Treatment Outcome

No abstract available.
Aminolevulinic Acid*

No abstract available.
Aminolevulinic Acid* ; Pemphigus, Benign Familial* ; Photochemotherapy*

In the present study, the effects of alpha lipoic acid (ALA) supplementation on glycemic control and lipid profile in streptozotocin (STZ)-induced diabetic rats have been evaluated. Sprague Dawley rats were divided into nondiabetic (NDM), diabetic without supplementation (No Suppl) and diabetic with ALA groups. ALA was orally administered once a day for 8 weeks with a dose of 100 mg/kg BW. Supplementation of ALA to STZ-induced rats prevented the severe damage to the islet cells of the pancreas and lowered the plasma glucose and glycated hemoglobin (HbA1c) levels. Supplementation of ALA also suppressed the increased of total cholesterol (TC), triglycerides and low density lipoprotein-cholesterol (LDL-C) levels in the plasma of diabetic rats as well as increased high density lipoproteincholesterol (HDL-C) levels. In conclusion, this study suggest that ALA may be effective in controlling glycemic status and improving dyslipidemia in streptozotocin-induced diabetic rats and has the potential in reducing cardiovascular complications due to diabetes mellitus.
Rattus norvegicus ; Streptozocin ; Aminolevulinic Acid ; Dyslipidemia ; Thioctic Acid

BACKGROUND: Photodynamic therapy with using 5-aminolevulinic acid (ALA) is a good noninvasive treatment modality that can treat several cutaneous diseases. Yet hydrophilic ALA is not able to easily penetrate the cellular membrane or the lipid layer of the skin. Thus, various ALA alkyl esters been developed. OBJECTIVE: We studied whether novel ALA unsaturated alkyl esters synthesize more protoporhyrin IX (PpIX) than does ALA in mouse skin tissues. METHODS: We applied 5, 10, 15% ALA and ALA esters ointment to the skin of shaved mice, respectively. We harvested the skin tissue, made a preparation and did quantitative analysis according to the fluorescent spectrum for determining the amount of PpIX synthesized in the skin after the elapse of 1 hour and 3 hours, respectively. RESULTS: No matter what the sort or the concentration of the ALA and ALA ester was, the amount of synthesized PpIX increased more after the elapse of 3 hours than that after 1 hour. ALA (hetenyl-, petenyl-, butenyl-, methyl-) esters tended to produce a much greater amount of PpIX than ALA. According to the results of the comparative study with using 5%, 10% and 15% of ALA and ALA esters ointment, the amount of synthesized PpIX was not proportional to the concentration of the ALA and the ALA esters, even though the ALA esters produced more PpIX than the ALA. CONCLUSION: We found that the ALA unsaturated alkyl esters are a good photosensitizer and they are similar to ALA-me, which is an ALA saturated alkyl ester that induces more PpIX, an actual photosensitizer, than ALA can.
Aminolevulinic Acid ; Animals ; Esters ; Membranes ; Mice ; Photochemotherapy ; Protoporphyrins ; Skin

For the purpose of establishing the preventive program against the health consequences of lead exposure and obtaining the effective biological monitoring data, the author investigated the values of biological parameters relating to lead exposure and the degree of influences on blood pressure level by these parameters including general characteristics in 192 female industrial workers dealing with lead(lead-exposed group) and 126 female official workers(non-exposed group). The summarized results were as follows; 1. Between the lead-exposed group and non-exposed group, the significant differences were showed in urinary coproporphyrin, urinary delta-aminolevulinic acid, urinary lead and blood lead amount. 2. Between the low blood lead group(less than 30 microgram/dl) and high blood lead group(more than 30 microgram/dl) in lead-exposed group, there were significant differences in systolic and diastolic blood pressure, urinary coproporphyrin, urinary lead and blood lead. 3. Among the parameters relating to lead exposure, the distribution of concentration of urinary coproporphyrin, urinary lead and blood lead showed normal distributed type in lead-exposed and non-exposed group. But the case of urinary delta-aminolevulinic acid showed bimodal type. On the other hand, dividing the lead-exposed group into low blood lead and high blood lead group, irregular distributed type were showed in all 4 kinds of parameters. 4. The parameters relating to lead exposure which showed significant correlation to blood pressure were absent in non-exposed group, but there were statistically significant simple correlation among the diastolic blood pressure and urinary lead and blood lead in high blood lead group. 5. The distribution of blood pressure by the concentration of parameters relating to lead exposure were not showed specific mode in non-exposed group, but there was increasing tendency with the higher concentration of parameters relating to lead exposure in lead-exposed group. Especially in high blood lead group, the increasing tendency of blood pressure with the level of urinary lead and blood lead were predominant. 6. The opportunity to explain variation of each blood pressure by the 4 kinds of parameters relating to lead exposure were 11.0-12.6% in lead exposed group and 12.0-15.4% in high blood lead group comparing to 5.3-6.1% in non-exposed group.
Aminolevulinic Acid ; Blood Pressure* ; Environmental Monitoring ; Female ; Hand ; Humans

Adult ; Aminolevulinic Acid ; urine ; China ; Female ; Humans ; Male ; Middle Aged

Adolescent ; Aminolevulinic Acid ; pharmacology ; Female ; Humans ; Porphyria, Acute Intermittent ; physiopathology

To investigate the effect of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) on () biofilm. biofilms were constructed on a cell slide and treated with ALA-PDT.According to different light doses,the biofilms were divided into six groups:ALA-PDT group [ALA-PDT1 (50 J/cm),ALA-PDT2 group (100 J/cm),ALA-PDT3 group (200 J/cm)],ALA-only group (ALA group),light-only group (LED),and a negative control group (ALA-PDT-group).The biofilm structure and the ratio of the dead bacteria/live bacteria were observed using a laser confocal microscope (CLSM).Biofilm viability was measured using the XTT assay. CLSM showed that the biofilm structures of ALA group and LED group were not significantly different from that of ALA-PDT-group,whereas the biofilm structure was more seriously damaged in ALA-PDT1 group,ALA-PDT2 group,and ALA-PDT3 group than in the ALA-PDT-group.The ratios of the dead/live bacteria in ALA-PDT-group,ALA group,LED group,ALA-PDT1 group,ALA-PDT2 group,and ALA-PDT3 group were 0.350±0.033, 0.305±0.046, 0.330±0.032, 1.525±0.439, 2.293±0.148 and 3.092±0.189,respectively.ALA group(=0.003, =1.000)and LED group(=-0.025, =1.000)did not significantly differ from the ALA-PDT-group.However,the ratio of dead/live bacteria in ALA-PDT-group was significantly lower than those in ALA-PDT1 group (=-0.162, <0.001),ALA-PDT2 group (=-0.254, <0.001),and ALA-PDT3 group (=-0.352, <0.001).The values of the XTT assay were were 0.462±0.028,0.465±0.044,0.437±0.047,0.301±0.040,0.207±0.001,and 0.110±0.007,respectively,in ALA-PDT-group,ALA group,LED group,ALA-PDT1 group,ALA-PDT2 group,and ALA-PDT3 group.Although the values of XTT assay in ALA(=-0.044, =1.000)and LED groups (=-0.020, =1.000)did not significantly differ from that in ALA-PDT-group,it was significantly higher in ALA-PDT-group than in ALA-PDT1 group (=1.175, <0.001),ALA-PDT2 group (=1.942, <0.001),and ALA-PDT3 group (=-0.352, =2.742, <0.001). ALA-PDT has an inhibitory effect on biofilm.ALA-PDT destroys biofilm structure and inhibits biofilm viability.
Aminolevulinic Acid ; Biofilms ; Photochemotherapy ; Photosensitizing Agents ; Propionibacterium acnes