Heme synthesis and

Lowest observed effect level (PbB) (Mg/dl) Heme synthesis and hematological effects Neurological effects Renal system effects Gastrointestinal effects ... 

Susceptibility to lead toxicity is influenced by dietary levels of calcium, iron, phosphorus, vitamins A and D, dietary protein, and alcohol (Calabrese 1978). Low dietary ingestion of calcium or iron increased the predisposition to lead toxicity in animals (Barton et al. 1978a Carpenter 1982 Hashmi et al. 1989a Six and Goyer 1972 Waxman and Rabinowitz 1966). Iron deficiency combined with lead exposure acts synergistically to impair heme synthesis and cell metabolism (Waxman and Rabinowitz 1966). 

Redig, P.T., E.M. Lawler, S. Schwartz, J.L. Dunnette, B. Stephenson, and G.E. Duke. 1991. Effects of chronic exposure to sublethal concentrations of lead acetate on heme synthesis and immune function in red-tailed hawks. Arch. Environ. Contam. Toxicol. 21 72-77. 

Lead (soft, Pb2+) Injuries to peripheral nervous system, disturbs heme synthesis and affects kidneys Pb2+ may replace Ca2+ with loss of functional and structural integrity. Reacts with sulfhydryl groups, replaces Zn2+ in 8-aminolevulinic acid dehydratase. 

Sucdnyl CoA is a high-energy intermediate that can be used for heme synthesis and to activate ketone bodies in extrahepatic tissues. 

Four intermediates in the TCA cycle serve as starting lints for compounds outside of the cycle. Oxaloacetate and i-ketoglutarate are used in the synthesis of several amino [rids, succinyl-CoA is used in heme synthesis and citrate is le source of the acetyl-CoA in the cytosol, which is used ir the synthesis of fats and other lipids and some amino ids. These are the major drains on the TCA cycle. 

Vanadium Vanadium is believed to be essential in certain animals, although there is still no evidence of this in humans. A V deficiency may alter Fe metabolism, impair heme synthesis, and affect lipid metabolism [15]. 

Biomarkers are related to different toxicants and organizational levels. Several examples are given in Table 9.12. Biomarkers range from those that are highly specific to those that are non-specific (a) those highly specific, as the enzyme aminolevulinic acid dehydratase (ALAD), which catalyzes a reaction involved in heme synthesis and is very sensitive to inhibition by inorganic lead (b) those non-specific, as effects in the immune system that can be caused by a wide variety of pollutants. 

Ascorbate is also active in the reduction of Fe + in the plasma transport protein, transferrin, to Fe + for storage in ferritin in the Uver or for heme synthesis. It is not clear to what extent this represents specific actions of ascorbate, because other reducing reagents, including glutathione, also enhance heme synthesis, and the NADH-dependent flavoprotein ferriductase is the major factor controlling the transfer of iron between transferrin and ferritin. 

Ryter SW, Tyrrell RM. The heme synthesis and degradation pathways role in oxidant sensitivity. Heme oxygenase has both pro- and antioxidant properties. Free Radic. Biol. Med. 2000 28 289-309. 

D. Valine is an essential amino acid and is not synthesized in the human. Glydne reacts with sucdnyl CoA in the first step of heme synthesis and with arginine in the first step of creatine synthesis. The entire glycine molecule is incorporated into the growing purine ring. 

The barbiturates induce drug-metabolizing enzymes, including the P450 system, leading to potential drug interactions. They also stimulate heme synthesis and are contraindicated in porphyrias. 

A. Hradilek, J. Neuwirt (1990). The relationship between heme synthesis and iron uptake in erythroid cells. Biomed. Biochim. Acta, 49, S94-99. 

General metabolic significance. Pyridoxine dependent enzymes catalyze almost exclusively reactions of amino acid metabolism, also participating in heme synthesis and generation of biogenic amines. 

Aminolaevulinic acid synthetase located in the mitochondrial matrix space (McKay et al, 1969) is the first in a sequence of enzymes involved in heme synthesis and may represent the rate limiting step in its regulation. This enzyme is not synthesized within the mitochondria (Jayaraman et al, 1971 Barnes et al, 1971). 

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