Hexachlorobenzene (HCB) is a persistent organic pollutant that caused a massive outbreak of porphyria cutanea tarda (PCT) in Turkey in 1959, and which is capable of inducing this human PCT type in several animal species. In spite of the great deal of information about the disturbances produced by HCB on heme metabolism leading to porphyria, scarce are those on other areas of Biochemistry. The present review describes the alterations that this porphyrinogenic fungicide produces in some aspects of: (1) The heme biosynthetic pathway. Molecular effects of HCB on the purified key uroporphyrinogen decarboxylase (URO-D) enzyme, its ability to generate URO-D inhibitor in vivo and in vitro, some physicochemical properties of such inhibitor, as well as the persistence of heme pathway alterations after discontinued HCB administration are summarized; (2) Lipid metabolism (phospholipids, eicosanoids, steroids, fatty acids), related with proliferation, destruction and fluidity of membranes and with genesis of pro-inflammatory metabolites; (3) Tryptophan metabolism (to serotonin, kynurenine, melatonin and other indoles). Alterations related with the oxidative stress picture, with the gluconeogenic blockade through the tryptophan level and potentially with cancer, are discussed; (4) Polyamine metabolism (putrescine, spermidine, and spermine levels and ornithine decarboxylase); (5) Carbohydrate metabolism (synthesis, degradation, transport, and storage of glucose, and pancreatic insulin secretion). Special attention has been devoted to the mechanism of gluconeogenesis blockade evaluating the role of free radicals, tryptophan, and glucocorticoid receptors. All these disturbances in relation to key parameters of porphyria and, in several cases, to those produced in the oxidative metabolism. The studies summarized in the present review were performed mainly in liver but also in other several tissues such as: kidney, brain, Harderian gland, pineal, blood and adrenals, trying to interconnect the spectrum of disturbances that this chlorinated pesticide exerts with the aim to have a more complete biochemical picture of the disease. All this is interesting both from biochemical and toxicological point of view.
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