Adrenoleukodystrophy protein

Synthesis of 22 6n-3 was not impaired in cell lines with X-ALD (Table 2), suggesting that the adrenoleukodystrophy protein (ALDP), a peroxisomal membrane protein that has been hypothesized to transport very-long-chain saturated fatty acids, does not participate in the retroconversion step of 24 6n-3 to 22 6n-3. The biosynthesis of 22 6n-3 was also normal in fibroblasts from patients with Refsum disease, who have a defect in peroxisomal fatty acid a-oxidation, indicating that a-oxidation does not contribute to 22 6n-3 synthesis. 

ALDP adrenoleukodystrophy protein BRCA- branched chain acyl- C24 ligno-ceric acid THCA trihydroxycoprostanic acid THC- trihydroxycoprostanoyl-. 

Adrenoleukodystrophy is an X-linked dysmyelinative disorder caused by mutations in the ABCD1 gene, which encodes the peroxisomal integral membrane ALD protein, a member of the ATP binding cassette transporter family. These mutations result in impaired clearance of plasma very-long-chain fatty acids. Affected males may present with symmetrical distal axonal polyneuropathy, adrenocortical insufficiency or CNS demyelination, while occasional heterozygous women demonstrate deficits suggestive of multiple sclerosis [56]. Manipulation of dietary fatty acid intake has some minimal therapeutic effect, while bone marrow transplantation has diminished deficits in a few patients. (See in Ch. 41.)... 

Adrenoleukodystrophy X-linked Peroxisomal membrane protein in the ABC transporter family Decreased peroxidation of saturated, very-long-chain fatty acids, causing their accumulation in brain, adrenals and other tissues variable phenotypes with regard to hypomyelination see text 1,26, Ch. 40... 

ALD adrenoleukodystrophy CaMK Ca2+-calmodulin-dependent protein kinase cyclic adenosine 3, 5 -monophosphate... 

Deficiency can lead to cancer and immune system dysfunction Stabilizes proteins used in the immune system Promotes membrane binding that is essential for proper protein localization or biological function May hinder progression of adrenoleukodystrophy Reduces low-density lipoprotein in the blood Reduces platelet stickiness and protects against coronary heart disease... 

There are many other neurodegenerative diseases, some with a high incidence, and others rare. They include Parkinson disease (p. 1790), Huntington disease (Table 26-4), spinal muscular atrophy (SMA a leading hereditary cause of infant mortality),1162a b amyotrophic lateral sclerosis (ALS), prion diseases (Box 29-E), ataxias, and other diseases caused by triple-repeat DNA sequences (Table 26-4) and X-linked adrenoleukodystrophy (ALD p. 945).1163 In the last, membrane function is disrupted. Although these diseases arise from a variety of causes many of them have in common amyloidosis, the deposition of insoluble proteins in or around neurons.11633... 

Feigenbaum, V., Lombard-Platct, G, Guidoux, S., Sarde, C.O., Mandel, J.L. Aubourg, P. (19%)4 n. J. Hum. Genet. 58, 1135-1144. Mutational and protein analysis of patients and heterozygous women with X-linked adrenoleukodystrophy. 

Four defined disorders of peroxisomal jff-oxidation have been identified including (1) X-linked adrenoleukodystrophy/adrenomyeloneuropathy, (2) acyl-CoA oxidase deficiency (3) D-bifunctional protein deficiency and (4) peroxisomal thiolase deficiency. The clinical presentation of the latter 3 disorders resembles that of the disorders of peroxisome biogenesis whereas the clinical presentation of X-linked ALD/AMN patients is completely different which explains why it is better to discuss this entity separately under d. 

X-linked adrenoleukodystrophy (XALD) ALD protein Generalized Xq28 300100... 

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