Heme synthesis—note that some reactions occur in the cytoplasm and some in the mitochondrion (yellow) In humans,<unk> s are the main precursors of heme, an essential constituent of hemoglobin, myoglobin, catalase, peroxidase, and P450 liver cytochromes. The body requires<unk> s to produce heme, which is used to carry oxygen in the blood among other things, but in the<unk> s there is a deficiency (inherited or acquired) of the enzymes that transform the various<unk> s into others, leading to abnormally high levels of one or more of these substances.<unk> s are classified in two ways, by symptoms and by pathophysiology. Physiologically,<unk> s are classified as liver or erythropoietic based on the sites of accumulation of heme precursors, either in the liver or in the bone marrow and red blood cells. Deficiency in the enzymes of the<unk>  pathway leads to insufficient production of heme. Heme function plays a central role in cellular metabolism. This is not the main problem in the<unk> s; most heme synthesis enzymes—even dysfunctional enzymes—have enough residual activity to assist in heme biosynthesis. The principal problem in these deficiencies is the accumulation of<unk> s, the heme precursors, which are toxic to tissue in high concentrations. The chemical properties of these intermediates determine the location of accumulation, whether they induce photosensitivity, and whether the intermediate is excreted (in the urine or feces). There are eight enzymes in the heme biosynthetic pathway, four of which—the first one and the last three—are in the mitochondria, while the other four are in the cytosol. Defects in any of these can lead to some form of<unk> . The hepatic<unk> s are characterized by acute neurological attacks (seizures, psychosis, extreme back and abdominal pain, and an acute polyneuropathy), while the erythropoietic forms present with skin problems, usually a light-sensitive blistering rash and increased hair growth.Variegate<unk>  (also<unk>  variegata or mixed<unk> , which results from a partial deficiency in PROTO oxidase, manifests itself with skin lesions similar to those of<unk>  cutanea tarda combined with acute neurologic attacks. Hereditary coproporphyria, which is characterized by a deficiency in coproporphyrinogen oxidase, coded for by the CPOX gene, may also present with both acute neurologic attacks and cutaneous lesions. All other<unk> s are either skin- or nerve-predominant.
Porphyria
Alcoholic liver disease
Chalicosis
Lead poisoning
Hepatic porphyria
Pellagra
Albinism
Harderoporphyria