Metabolic injury, heavy metal

Events such as progression through the cell cycle and differentiation or environmental stresses such as heat, oxidative injury, heavy metals, inhibitors of energy metabolism, or pathological conditions such as inflammation, all result in the expression of HSPs which are considered to have essential protective functions in cells... 

The role of GSH in cellular protection (see below) means that if depleted of GSH, the cell is more vulnerable to toxic compounds. However, GSH is compartmentalized, and this compartmentalization exerts an influence on the relationship between GSH depletion or oxidation and injury. The loss of reduced GSH from the cell leaves other thiol groups, such as those in critical proteins, vulnerable to attack with subsequent oxidation, cross-linking, and formation of mixed disulfides or covalent adducts. The sulfydryl groups of proteins seem to be the most susceptible nucleophilic targets for attack, as shown by studies with paracetamol (see chap. 7), and are often crucial to the function of enzymes. Consequently, modification of thiol groups of enzyme proteins, such as by mercury and other heavy metals, often leads to inhibition of the enzyme function. Such enzymes may have critical endogenous roles such as the regulation of ion concentrations, active transport, or mitochondrial metabolism. There is... 

Heavy metals stimulate or inhibit a wide variety of enzyme systems (16, 71, 72), sometimes for protracted periods (71, 73). These effects may be so sensitive as to precede overt toxicity as in the case of lead-induced inhibition of 8 ALA dehydrase activity with consequential interference of heme and porphyrin synthesis (15, 16). Urinary excretion of 8 ALA is also a sensitive indicator of lead absorption (74). Another erythrocytic enzyme, glucose-6-phosphatase, when present in abnormally low amounts, may increase susceptibility to lead intoxication (75), and for this reason, screens to detect such affected persons in lead-related injuries have been suggested (76). Biochemical bases for trace element toxicity have been described for the heavy metals (16), selenium (77), fluoride (78), and cobalt (79). Heavy metal metabolic injury, in addition to producing primary toxicity, can adversely alter drug detoxification mechanisms (80, 81), with possible secondary consequences for that portion of the population on medication. 

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