Albinism metabolism

Albinism refers to a group of conditions in which a defect in tyrosine metabolism results in a deficiency in the production of melanin. These defects result in the partial or full absence of pigment from the skin, hair, and eyes. Albinism appears in different forms, and it may be inherited by one of several modes autosomal recessive, autosomal dominant, or X-linked. Complete albinism (also called tyrosinase-negative oculocutaneous albinism) results from a defi ciency of tyrosinase activity, causing a total absence of pigment from the hair, eyes, and skin (Figure 20.20). It is the most severe form of the condition. Affected people may appear to have white hair, skin, and iris color, and they may have vision defects. They also have photophobia (sunlight is painful to their eyes), they sun burn easily, and do not tan. 

Examples of other important genetic diseases associated with amino acid metabolism Other important genetic diseases associated with amino acid metabolism include albinism, homocystinuria, methylmalonyl CoA mutase deficiency, alkaptonuria, histidinemia, and cystathioninuria. 

Enzyme deficiency diseases. A variety of metabolic diseases are caused by deficiencies or malfunctions of enzymes, due originally to gene mutation. Albinism, for example, may be caused by the absence of tyrosinase, an enzyme essential for the production of cellular pigments. The hereditary lack of phenylalanine hydroxylase results in the disease phenylketonuria (PKU) PKU is usually managed by dietary modifications, but intravenous... 

Phenylketonuria, alcaptonuria, and albinism are caused by deficiencies in enzymes involved in the metabolism of... 

Melanin is the normal pigment of the skin and mammalian hair. Carcinomatous growths in which abnormal melanin formation occurs are known as melanomas. A congenital metabolic defect in w hich skin pigmentation does not occur is known as albinism, and is inherited as a recessive Mende-lian character (cf. 40). Albinos occur in many species besides man (e.g., the pink-eyed white rabbit). As adrenaline formation is apparently unimpaired in albinos, the metabolic block presumably lies in the conversion of dihydroxyphenylalanine to melanin, as shown in diagram 6, rather than in the conversion of tyrosine to dihydroxyphenylalanine. However, the exact nature of the block has not been established. 

Copper is necessary, together with iron, for hematopoiesis, probably partly because it is needed for the synthesis of fer-roxidase (ceruloplasmin). Many enzymes require copper for activity. Examples of some of the copper-enzymes and their functions are given in Table 37-5. Mitochondrial iron uptake may be blocked by deficiency of a cuproprotein, perhaps cytochrome oxidase. Several inherited diseases involving abnormalities in copper metabolism (Wilson s disease, Menkes syndrome) or copper enzymes (X-linked cutis laxa, albinism) occur in human and in several animal species. 

Beelen R, Hoek G, Houthuijs D, van den Brandt PA, Goldbohm RA, Fischer P, Schouten LJ, Armstrong B, Brunekreef B (2009) The joint association of air pollution and noise from road traffic with cardiovascular mentality in a cohort study. Occup Environ Med 66 243-250 Binkova B, Chvatalova I, Lnenickova Z, Milcova A, Tulupova E, Farmer PB, Sram RJ (2007) PAH-DNA adducts in environmentally exposed population in relation to metabolic and DNA repair gene polymorphisms. Mutat Res 620 49-61 Bjork J, Ardo J, Stroh E, Lovkvist H, Ostergren PO, Albin M (2006) Road traffic noise in southern Sweden and its relation to annoyance, disturbance of daily activities and health. Scand J Work Environ Health 32 392-401... 

Scriver CR. Garrod s Croonian lectures (1908) and the charter inborn errors of metabolism albinism, alkaptonuria, cystinuria, and pentosuria at age 100 in 2008. J Inherit Metab Dis. 2008 31(5) 580-98. 

In alkaptonuria, homogentisic acid (28) is excreted in excessive amounts indicating that in this metabolic disease the opening of the aromatic ring and complete oxidation to CO2 and H2O is blocked. In albinism, there is a deficiency of the enzyme systems responsible for the formation of melanin from tyrosine (24) (Figure 3.7). 

Drug-Induced Hemolytic Anemia 170 Inborn Errors of Aromatic Amino Acid Metabolism 172 Phenylketonuria Tyrosinosis Alkaptonuria Albinism Histidinemia... 

There are two forms of oculocutaneous albinism a tyrosinase negative due to a tyrosinase defect and a tyrosinase positive of unknown origin (probably caused by inavailability of tyrosine to the melanocyte). Both forms are inherited as autosomal recessive traits, but the genes for each type are found in different loci. Ocular albinism is inherited as an X-linked recessive trait. It is associated with vision defects, nystagmus, and head nodding. The metabolic defect is unknown. 

L-dopaquinone (36). Figure 4.14. The conversion of L-dopaqxiinone (36) to dopa-melanin is then assumed to be spontaneous. Albinism, which is characterised in mammals by a complete or partial lack of melanin pigments in the skin and hair, results from a deficiency in tyrosinase activity. It represents a further example of a disease which has resulted from an inborn error of metabolism . 

INBORN ERRORS OF THE METABOLISM. At times the metabolism of the nutrients cannot proceed normally due to some defect in the genetic information that exists at birth or shortly thereafter. These defects can affect the metabolism of carbohydrates, proteins, and fats hence, they are referred to as inborn errors of metabolism. Often they are due to production of a nonfunctional enzyme or complete lack of an enzyme involved in the metabolic scheme. Since enzymes are protein, their production relies upon correct genetic information. Many of these inborn errors have serious consequences, but fortunately most are rare. Familiar examples of errors in carbohydrate metabolism include lactose intolerance and galactosemia. Familiar examples of errors in protein metabolism include albinism, maple syrup urine disease, and phenylketonuria. The hyperlipoproteinemias are familiar examples of inborn errors of fat metabolism. 

Occasionally, individuals are born with very specific disorders related to the metabolism of protein or amino acids. These are often referred to as inborn errors of metabolism. Albinism, maple syrup urine disease, and phenylketonuria are examples of some of the more familiar types. 

The only known inborn error of metabolism that can be linked to a copper-dependent enzyme is albinism, A genetically acquired absence of the enzyme tyrosinase results in albinism, which is characterized by the complete lack of pigmentation in the eyes and integument. Tyrosinase is essential in the pigmentation process because this enzyme catalyzes the first two steps in the synthesis of melanin pigment from tyrosine. Mammals that lack pigment do not have the capability to filter the sun s ultraviolet rays, which penetrate the integument and cause molecular havoc. 

Much of the earlier knowledge of the metabolic pathways of phenylalanine and tyrosine was obtained by the study of the defects in the hereditary diseases, alcaptonuria, albinism, phenylpyruvic oligophrenia, and tyrosinosis. Widespread interest in this subject dates from the publication of Garrod s Inborn Errors of Metabolism (2). The metabolic Uoeka at particular steps in the degradative pathways of phenylalanine and tyrosine for the disorders mentioned above are shown in Fig. 15. 

The amino acid tyrosine is needed in the formation of melanin, the pigment that gives the color to our skin and hair. If the enzyme that converts tyrosine to melanin is defective, no melanin is produced and a genetic disease known as albinism results. Persons and animals with no melanin have no skin, eye, or hair pigment (see Figure 17.16). Table 17.8 lists some other common genetic diseases and the type of metabolism or area affected. 

---