8-amino levulinic acid

Acute intermittent porphyria is a dominantly inherited partial deficiency of porphobilinogen deaminase, and causes axonal polyneuropathy. Acute intermittent porphyria is caused by partial deficiency of porphobilinogen deaminase, an enzyme required for heme biosynthesis. Patients may present with acute abdominal pain, rapidly progressive sensorimotor axonal polyneuropathy or psychosis, and have elevated concentrations of the heme precursor 8-amino-levulinic acid in their urine. Symptoms may be precipitated by treatment with barbiturates or other drugs and are suppressed by treatment with hematin [59]. 

Urine ( -aminolevuli nic acid) Dilution of sample reaction with ethylacetoacetate and ethylacetate to form -amino-levulinic acid-pyrrole reaction with Erhlich s reagent Spectrophotometry No data No data Tomokuni and Ichiba 1988... 

Beside the use of a single enzyme, a cocktail of different biocatalysts can also be used in performing a domino process, provided that the enzymes do not interfere one with another. This approach was used by Scott and coworkers in the synthesis of precorrin-5 (8-61) (Scheme 8.16) [24]. Starting from 6-amino levulinic acid (ALA) 8-60, a mixture of eight different enzymes including the ALA-dehydratase to form porphobilinogen (PBG), as well as PBG deaminase and co-synthetase to furnish the tetracyclic uroporphyrinogen III (8-62) as intermediates, was employed to provide precorrin-5 (8-61) in 30% yield. 

Hodson, P.V. 1976. d-amino levulinic acid dehydratase activity of fish blood as an indicator of a harmful exposure to lead. Jour. Fish. Res. Board Can. 33 268-271. 

Dec-trans-4-enoic acid, 3-hydroxy-6-iso-pro-pyl-3-methyl-9-oxo, (6S) Lf 0.037 Dec-trans-4-enoic acid, 3-hydroxy-6-iso-pro-pyl-3-methyl-9-oxo Lf 0.008 Dehydratase, A-amino-levulinic acid ... 

Mauzerall D, Granick S (1995) The occurrence and determination of delta-amino-levulinic acid and porphobilinogen in urine. J Biol Chem 219 435-446... 

Studies in animals suggest that chlorobenzene may also cause injury to the liver. In rats, alkaline phosphatase, SGOT, and delta-amino levulinic acid levels were increased as were liver protoporphyrin and uroporphyrin. Data suggest that the kidneys may be affected following exposure to chlorobenzene as polyuria was noted in rats at high dose levels. Since other chemicals may produce similar effects, these are not specific indicators of chlorobenzene exposure. 

Mocarelli et al. (1986) conducted a 6-year study on clinical laboratory parameters of children exposed to 2,3,7,8-TCDD following the Seveso accident. ALT, aspartate aminotransferase (AST), GGT, alkaline phosphatase, cholesterol, and triglycerides in plasma and delta amino levulinic acid in urine were monitored yearly in exposed and control groups beginning in June, 1977, approximately 1 year after the incident. The children were 6-10 years old at the time of the accident 69, 528, and 874 resided in the A, B, and R zones, respectively. Chloracne was seen in 19, 0.7, and 4.6%, of the children in areas A, B, and R, respectively. Blood samples were drawn from 69, 83, and 221 children in areas A, B, and R,... 

The precursor for vitamin B12 synthesis is uroporphyrinogen 111, the common precursor for aU porphyrins, including heme and chlorophyll. Uroporphyrinogen III is synthesized by condensation between succinyl coenzyme A (CoA) and glycine to yield 5-aminolevulinic acid. Two molecules of (5-amino-levulinic acid then condense to form the pyrrole phorphobilinogen, and four molecules of porphobilinogen condense to yield uroporphobilinogen III. 

Permanence of response. Similarly, it is important to know how long the response lasts. If it is transient, it may readily be missed. The inhibition of AChE, especially in blood, is a transient response and thus it is necessary to know when the exposure occurred to assess the importance of the degree of inhibition. In contrast, the inhibition the enzyme amino levulinic acid dehydratase by lead is only slowly reversed. 

Cobalt most often depresses the activity of enzyme including catalase, amino levulinic acid synthetase, and P-450, enzymes involved in cellular respiration. The Krebs citric acid cycle can be blocked by cobalt resulting in the inhibition of cellular energy production. Cobalt can replace zinc in a number of zinc-required enzymes like alcohol dehydrogenase. Cobalt can also enhance the kinetics of some enzymes such as heme oxidase in the liver. Cobalt interferes with and depresses iodine metabolism resulting in reduced thyroid activity. Reduced thyroid activity can lead to goiter. 

The rehydration product of HMF, levulinic acid, is also regarded as a potential biomass derived organic compound [35, 39,40]. Levulinic acid could be utilized as feedstock for several large volume chemicals (Fig. 7), e.g., methyltetrahydrofuran and levulinate esters (fuel additives), delta-amino-levulinic acid (herbicide), and diphenohc acid (replacer for bisphenol A for polycarbonates). 

Chang, S.C., MacRobert, A.J., Porter, J.B., and Bown, S.G. (1997) The efficacy of an iron chelator (CP94) in increasing cellular protoporphyrin IX following intravesical 5-amino-levulinic acid administration an in vivo study, J. Photochem. Photobiol. B Biol., 38 114-122. 

Kennedy, J.C., Marcus, S.L., and Pother, R.H. (1996) Photodynamic therapy (PDT) and photodiagnosis (PD) using endogenous photosensitizahon induced by 5-amino-levulinic acid (ALA) mechanisms and clinical results, J. Clin. Laser Med Surg., 14 289-304. 

Soler, A.M., Angell-Petersen, E., Warloe, T., Tausjo, J., Steen, H.B., Moan, J., and Giercksky, K.E. (2000) Photodynamic therapy of superficial basal cell carcinoma with 5-amino-levulinic acid with dimethylsulfoxide and ethylendiaminetetraacetic acid a comparison of two hght sources, Photochem. Photobiol., 71 724—729. 

Intoxication. This indicates that the absorbed lead is having adverse metabolic effects upon a body tissue. The toxicity is proportional to the concentration of lead at the site. Defining minimal manifestations of toxicity has extended with our increasing ability to develop sensitive indices of toxicity. Inhibition of delta-amino levulinic add dehydratase with an increase in urinary amino-levulinic acid is a relatively sensitive index of toxidty in intoxication, indicating that the lead is having an adverse effect on porphyrin metabolism... 

An example of an indirect marker of xenobiotic-in-duced renal disease is the elevated level of red cell content of either delta amino-levulinic acid dehydrase or free erythrocyte protoporphyrin in patients with lead nephrotoxicity [3,4]. Direct examples of biomarkers of... 

Borohydride trapping was also used to demonstrate the presence of an iminium ion in the pathway involved in pyrrole biosynthesis from two molecules of A-amino-levulinic acid [123]. This reaction, shown in Scheme 23, involves iminium ion formation with 1 mole of substrate, eneamine formation by deprotonation, and then... 

At least three polymorphic genes have been identified that potentially can influence the bioaccumulation and toxicokinetics of lead in humans (1) the gene coding for 6-amino-levulinic acid dehydratase (ALAD) (2) the Vitamin D receptor (VDR) gene and (3) HFE, the gene for hereditary hemochromatosis (Onalaja et al. 2000). 

Figure 2-3 The catalytic mechanism of ALAS as proposed by Jordan [66], The reaction mechanism involves the formation of a Schiff base linkage between glycine and the PLP cofactor. Removal of the pio-R proton yields a carbanion which reacts with the second substrate, succinyl-CoA. Note the retention of the pro-5 proton of glycine in the pro-5 position of C-5 of ALA. ALA, 5-amino-levulinic acid.

Y. Itoh, T. Henta, Y. Ninomiya, S. Tajima, A. Ishibashi (2000). Repeated 5-amino-levulinic acid-based photodynamic therapy following electro-curettage for pigmented basal cell carcinoma. J. Dermatol., 27, 10-15... 

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