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Study on peroxisome Pharmaceutics

The discovery of peroxisome

First discovered by J. Rhodin (1954) in mouse renal tubular epithelial cells. Is a heterogeneous organelle, in different biological and different developmental stages are different. Diameter of about 0.2 ~ 1.5um, usually 0.5um, was round, oval or dumb-shaped ranging from single-layer membrane is formed. A common feature is that one or more dependent on flavin (flavin) oxidase and catalase (marker enzyme), has been found in more than 40 kinds of oxidase, such as L-amino acid oxidase, D-amino acid oxidase, The uric acid oxidase (urate oxidase) content is extremely high, so that in some species form the core of the enzyme crystal composition. The left shows a crystalline core with uric acid oxidase formation in the center.

Peroxisomal morphology

Peroxisome (peroxisome), also known as microbody (microbody), peroxisomal body was discovered in 1954, due to the function of this particle is not known, it is called microbody (microbody). Peroxisome (peroxisome) is an organelle, present in all cells, containing about 40 kinds of oxidase and catalase, the main function is to catalyze the β-oxidation of fatty acids, the very long chain fatty acid (very long chain fattyacid , VLCFA) into short chain fatty acids. Peroxisomes are vesicles surrounded by a layer of monolayers of about 0.5 to 1.0 μm in diameter, usually smaller than mitochondria. Unlike lysosomes, peroxisomes do not originate from the endoplasmic reticulum and the Golgi apparatus, so they are not membrane-bound organelles of the endometrial system. Peroxisomes are ubiquitous in various types of eukaryotic cells, but in liver cells and kidney cells in a particularly large number. Peroxisomes are rich in enzymes, mainly oxidase, catalase and peroxidase. Oxidases can act on unused substrates, and their common feature is to oxidize the substrate while reducing oxygen to hydrogen peroxide. Peroxisomal marker enzyme is a catalase, its role is mainly to hydrogen peroxide (H2O2, Hydrogen Peroxide) hydrolysis. Hydrogen peroxide (H2O2) is a cytotoxic substance produced by the oxidation-reduction reaction catalyzed by oxidase. Oxidases and catalases are present in the peroxisomes, thus protecting the cells.

Peroxisomal functional response

Features: (1) inactivation of toxic substances

This action is the use of hydrogen peroxide hydrogen peroxide oxidation of various substrates, such as phenol, formic acid, formaldehyde and ethanol, the oxidation of these toxic substances into non-toxic substances, but also to further change H2O2 Into non-toxic H2O. This detoxification is particularly important for the liver and kidneys, for example, almost half of the ethanol that people drink is oxidized to acetaldehyde in this way, thereby relieving the toxic effects of ethanol on cells.

(2) the regulation of oxygen concentration

Peroxisomes and mitochondria are not the same for oxygen sensitivity, mitochondrial oxidation required for the best oxygen concentration of about 2%, increasing the oxygen concentration, does not improve the oxidation capacity of mitochondria. The rate of peroxisomal oxidation increases proportionally as the oxygen tension increases. Thus, under low concentrations of oxygen, mitochondria use oxygen to be more potent than peroxisomes, but in the presence of high concentrations of oxygen, peroxisomal oxidation dominates, The lysosome has a toxic effect on cells from high concentrations of oxygen.

(3) oxidation of fatty acids

Approximately 25 to 50% of the fatty acids in animal tissues are oxidized in the peroxisomes and others in the mitochondria. In addition, peroxisomes are also involved in the synthesis of lipids because of the enzymes involved in the synthesis of phospholipids in the peroxisomes.

(4) the metabolism of nitrogenous substances

In most animal cells, urate oxidase (urate oxidase) for uric acid oxidation is necessary. Uric acid is the product of nucleotides and certain protein degradation, uric acid oxidase can be further oxidation of this metabolic waste removal. In addition, peroxisomes are also involved in other nitrogen metabolism, such as transaminases (aminotransferase) catalytic amino transfer.

reaction: Common types of oxidase is the oxidation of the substrate to generate hydrogen peroxide.

Classification of Peroxisomes

Peroxisomes in animals:

In animals, peroxisomes are involved in β-oxidation of fatty acids (the other organelle is mitochondria). The enzyme concentration of hepatic peroxisomes increases 10-fold after taking lipid-lowering agents. In addition, peroxisomes also have detoxification, because catalase can use H2O2 phenol, formaldehyde, formic acid and alcohol and other harmful substances oxidation, into the alcohol 1/4 is oxidized in the peroxisome B aldehyde.

Peroxisomes in plants:

In plant peroxisomes are: 1). involved in photorespiration, the photosynthesis by-product of glycolic acid oxidation of glyoxylic acid and hydrogen peroxide, 2). in the germination of the seeds, the fat β-oxidation, resulting in Acetyl-CoA, the glyoxylic acid cycle, from isocitric acid for the decomposition of glyoxylic acid and succinic acid, adding tricarboxylic acid cycle, involving glyoxylic acid cycle, also known as glyoxylic acid cycle (glyoxysome).

Peroxisomal evolutionary angle

From the point of view of phylogeny, peroxisomes may be an ancient organelles. After the appearance of photosynthetic organisms, the oxygen content in the atmosphere gradually increases, while the intracellular oxygen is toxic to the early organisms. The function of the lysosome is to eliminate intracellular oxygen and produce some of the metabolites required by the cell. Although a simple respiratory chain can be formed between the flavin, oxidase and catalase in the peroxisomes, it does not function as an energy converter. Subsequent mitochondrial generation replaces this function of the peroxisomes and their electron transport is coupled to ATP synthesis.

Peroxisomes are derived from the division of existing peroxisomes from the viewpoint of individual occurrence. All the enzymes in the peroxisomes are encoded by the nuclear gene, synthesized in the cytoplasmic matrix, introduced into the peroxisomes under the guidance of the signal peptide, and the signal sequence leading the protein into the peroxisomes is -Ser- Lys-Leu-COO-. But little is known about the receptors and transposable elements associated with protein entry in the peroxisomal membrane, at least in relation to 23 proteins known as peroxins, whose mechanism is significantly different from mitochondrial and chloroplast protein transport, Body Pex5 (a peroxin) is associated with the cargo entering the peroxisomes and then returning to the cytoplasm.

Peroxisomal initiation of disease

Peroxisomal disease, plasma, fibroblasts, amniotic fluid cells in the VLCFA increased. In recent years, more and more cases of peroxisomal disease have been found, there are various types of adrenal leukodystrophy (adrenoleukodystrophies), brain and liver syndrome (Zellweger disease), infant Refsum disease, high six Hyperpipecolic acidemia, rhizomelic chondrodysplasiapunctata, and the like.

Zellweger syndrome is a class of peroxisomal-related genetic disease, also known as the brain and liver and kidney syndrome, the cells of the peroxisomes, enzyme protein input related protein variation, peroxisomes are " empty". Brain, liver, kidney abnormalities, died within 3-6 months after birth.

 


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Read:  2016-12-30 14:24:59  Glory Science Life science source - ELISA Kits - Antibodies - Research Products
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