8-Aminolevulinic acid synthetase

Narayan S, Misra UK. 1985. Delta-aminolevulinic acid synthetase and heme oxygenase activity in lung and liver of rats given DDT and endosulfan intratracheally. Bull Environ Contam Toxicol 34 24-28. 

Decrease in weight gain moderate liver pathology gross accumulations of hepatic porphyrins and increased delta-aminolevulinic acid synthetase activity Decrease in weight gain comparatively small increase in liver weight... 

Pretreatment with the Type I substrate, ethylmorphine, resulted in 100% mortality in both rats and mice, and aminopyrine pretreatment resulted in 100% and 64% mortality in rats and mice, respectively, exposed to disulfoton (Pawar and Fawade 1978). Nickel chloride, cobalt chloride, or cycloheximide decreased the levels of cytochrome bs, cytochrome c reductase, and total heme in rats (Fawade and Pawar 1983). These electron transport components were further decreased in rats pretreated with these inhibitors and given a single dose of disulfoton. Data from this study suggests an additive effect, since disulfoton also decreases the activities of these components. Evidence of an additive effect between disulfoton and these metabolic inhibitors was suggested by the decrease in ethylmorphine N-demethylase and acetanilide hydroxylase activities when rats were given an inhibitor followed by disulfoton. In another experiment, these inhibitors decreased the activity of delta-aminolevulinic acid synthetase, but this decrease was reversed when disulfoton was administered. 

Cadmium in the body is known to affect several enzymes. It is believed that the renal damage that results in proteinuria is the result of cadmium adversely affecting enzymes responsible for reabsorption of proteins in kidney tubules. Cadmium also reduces the activity of delta-aminolevulinic acid synthetase (Figure 10.3), arylsulfatase, alcohol dehydrogenase, and lipoamide dehydrogenase, whereas it enhances the activity of delta-aminolevulinic acid dehydratase, pyruvate dehydrogenase, and pyruvate decarboxylase. 

Poland A, Glover E. 1973a. Chlorinated dibenzo-p-dioxins Potent inducers of delta-aminolevulinic acid synthetase and aryl hydrocarbon hydroxylase 2. Study of the structure-activity relationship. Mol Pharmacol 9 736-747. 

Iron regulatory proteins (IRPs) regulate the cellular iron level in mammalian cells. IRPs are known as cytosol mRNA binding proteins which control the stability or the translation rate of mRNAs of iron metabolism-related proteins such as TfR, ferritin, and 5-aminolevulinic acid synthetase in response to the availability of cellular iron [19-21] after uptake [5]. The regulatory mechanism involves the interaction between the iron-responsive element (IRE) in the 3 or 5 untranslated regions of the transcripts and cytosolic IRPs (IRP-1 and -2). IRP-1 is an iron-sulfur (Fe-S) protein with aconitase activity containing a cubane 4Fe-4S cluster. When Fe is replete, IRP-1 prevails in a 4Fe-4S form as a holo-form and is an active cytoplasmic aconitase. As shown in Fig. 3, when Fe is deplete, it readily loses one Fe from the fourth labile Fe in the Fe-S cluster to become a 3Fe-4S cluster and in this state has little enzymatic activity [22, 23]. 

The hematopoietic system is affected by both short- and long-term arsenic exposure. Arsenic is known to cause a wide variety of hematological abnormalities like anemia, absolute neutropenia, leucopenia, thrombocytopenia, and relative eosinophilia - more common than absolute esino-philia, basophilic stippling, increased bone marrow vascularity, and rouleau formation (Rezuke et al, 1991). These effects may be due to a direct hemolytic or cytotoxic effect on the blood cells and a suppression of erythropoiesis. The mechanism of hemolysis involves depletion of intracellular GSH, resulting in the oxidation of hemoglobin (Saha et al, 1999). Arsenic exposure is also known to influence the activity of several enzymes of heme biosynthesis. Arsenic produces a decrease in ferrochelatase, and decrease in COPRO-OX and increase in hepatic 5-aminolevulinic acid synthetase activity (Woods and Southern, 1989). Subchronic... 

The most common cause of iron overload is thalassemia, particularly in the parts of the world where it is prevalent (see earlier section). Indeed, the cardiac complications of iron overload are among the most common causes of death in I-thalassemia major. Sideroblastic anemias are a group of iron-loading disorders, many of which are of unknown cause. In a hereditary type of this disorder, there is deficiency of erythroid specific 5-aminolevulinic acid synthetase in RBC precursors because of mutations involving the X-linked gene that encodes this enzyme. Iron storage is common in patients with congenital dyserythropoietic anemia and may be found in patients with red cell enzyme deficiencies, particularly pyruvate kinase deficiency. ... 

The therapeutic efficacy of oral administration of seed powder of M. oleifera (500 mg/kg, orally, once daily) post arsenic exposure (100 ppm in drinking water for 4 months) in rats has been investigated (49). Animals exposed to arsenic(lll) shows a significant inhibition of 8-aminolevulinic acid dehydratase (ALAD) activity, decrease in reduced glutathione (GSH) level and an increase in reactive oxygen species (ROS) in blood. On the other hand, a significant decrease in hepatic ALAD, and an increase in 8-aminolevulinic acid synthetase (ALAS) activity is observed after arsenic exposure. These changes... 

All of the nitrogen in heme is derived from glycine and all of the carbons are derived from succinate and glycine. Thus, the process by which heme is synthesized is also called the succinate-glycine pathway. The first step in the process is catalyzed by a pyridoxal phosphate-containing enzyme, 5-aminolevulinic acid synthetase (ALA synthetase)... 

Oncogene products Ornithine decarbosiylase, tyrosine atninotranslerase, protein kinase C Aminolevulinic acid synthetase HMG-CoA reductase... 

Bissell, D. M., and Hammaker, L. E. (1976b). Cytochrome p-450 heme and the regulation of S-aminolevulinic acid synthetase in the liver. Arch. Biochem. Biophys. 176, 103-112. 

S. Granik, S. Sassa (1971). 5-Aminolevulinic acid synthetase and control of heme and chlorophyll synthesis. In H.J. Vogel (Ed.), Metabolic Regulation (pp. 77-141) McGraw-Hill, New York. 

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