Peroxisomal Diseases

Abstract

The peroxisomal diseases, which are rare inborn metabolic errors, often have serious effects on the well being of the individual and many of them are fatal at an early age. The Zellweger cerebro-hepato-renal syndrome represents a group consisting of diseases with a generalized loss of peroxisomal functions and is considered as a prototype for peroxisomal dysfunction. The largest group includes those diseases where only a single peroxisomal function is impaired. The most common peroxisomal disease, x-linked adrenoleukodystrophy (ADL), belongs to this group, and neurological symptoms dominate among the patients. The primary diagnosis is usually based on clinical findings and measurement of accumulated or depleted metabolites in the body (e.g. very long chain fatty acids, bile acid intermediates or plasmalogens). Some progress has been made in treating of the peroxisomal diseases. Many patients with x-linked ALD have benefitted from the supplementation of the diet with long chain monounsaturated fatty acids like erucic acid or oleic acid with the simultaneous restriction of very long chain fatty acids. Docosahexenoate (C22:1) has also shown promising results in some studies.

Structural studies on Δ3‐Δ2‐enoyl‐CoA isomerase: the variable mode of assembly of the trimeric disks of the crotonase superfamily

“…To further analyze the properties of Eci1p at different pHs, the pH optimum of its enzyme activity was determined. The enzyme assays were performed according to a published method [14] using 80 μM trans ‐3‐hexenoyl‐CoA as substrate. The k cat values of Eci1p were measured from duplicate samples at each of the following pH values: 7.0, 7.5, 8.0, 8.5, 9.0, 9.3, 9.5 and 9.8.…”

Genome-wide association studies with metabolomics

“…In the past, candidate gene and pedigree analyses were very successful in the study of diseases of monogenetic origin: heritable dysregulation of certain metabolomic traits (inborn errors of metabolism) were among the first to be associated with specific genes [4]. However, these approaches are not useful in complex diseases because candidate regions contain too many genes or there are no groups of related individuals with a clear inheritance pattern of the disease phenotype.…”

Mitochondrial 3-2trans-Enoyl-CoA Isomerase. Purification, Cloning, Expression, and Mitochondrial Import of the Key Enzyme of Unsaturated Fatty acidβ-Oxidation

“…All three enzymes have been cloned^2 3~25 l It has been reported recently that the peroxisomal bifunctional enzyme exhibits an additional 3-2iran5'-enoyl-CoA-isomerase activity and should be regarded as a trifunctional enzyme [26] . In E. coli the enzyme activities required for the /3-oxidation of saturated and unsaturated fatty acids are assembled as a multienzyme complex with tetrameric structure consisting of two ex-and two/S-subunits.The Brought to you by | New York University Bobst Library Technical S Authenticated Download Date | 5/27/15 9:50 AM α-subunit of 79 kDa is encoded within the fad B operon and forms a multifunctional enzyme with the enzyme activities of enoyl-CoAhydratase, L(+)3-hydroxyacyl-CoA dehydrogenase, 3-2ira«s-enoyl-CoA isomerase and D(-)3-hydroxyacyl-CoA epimerase, whereas the two identical small /3-subunits, associated with the 3-ketoacyl-CoA-thiolase activity are encoded in the fad A operon [27i .…”