FUNCTIONS OF PEROXISOMES

SHREYA AHUJAROLL NO. 11

Microbody organelles

found in the cytoplasm

PEROXISOMES in higher

eukaryotic cells.

GLYCOSOMES in

kinetoplastids

GLYOXYSOMES in plant cells

• Related microbody organelles that perform differing metabolic functions tailored to their cellular environments.

• The close evolutionary relationship of these organelles is most clearly evidenced by the conservation of proteins involved in matrix protein import and biogenesis.

Oxidation reactions leading to the production of hydrogen peroxide. Because hydrogen peroxide is harmful to the cell, peroxisomes also contain the enzyme catalase, which decomposes hydrogen peroxide either by converting it to water or by using it to oxidize another organic compound.

Peroxisomes are involved in lipid biosynthesis. In animal cells, cholesterol and Dolichol are synthesized in peroxisomes as well as in the endoplasmic reticulum

In plants, peroxisomes in seeds are responsible for the conversion of stored fatty acids to carbohydrates, which is critical to providing energy and raw materials for growth of the germinating plant.

Peroxisomes in leaves are involved in photorespiration, which serves to metabolize a side product formed during photosynthesis.

MAIN FUNCTIONS OF PEROXISOMES

OXIDATION REACTIONS OF PEROXISOMES A variety of substrates are broken down by such oxidative reactions in peroxisomes, including uric acid, amino acids, and fatty acids. The

oxidation of fatty acids is a particularly important example, since it provides a major source of metabolic energy. In animal cells, fatty acids are oxidized in both peroxisomes and mitochondria, but in yeasts, fatty acid oxidation is restricted to peroxisomes.

Beta oxidation of fatty acids occurs in the peroxisomes (a eukaryotic organelle) in addition to the mitochondria, though in a modified form.

A primary function of peroxisomal beta oxidation is to shorten very long chain fatty acids so they can be degraded in the mitochondrion.

Peroxisomal oxidation has advantages over mitochondrial oxidation - fatty acids can diffuse across the peroxisomal membrane. After very long chain fatty acids are partly degraded, they are attached to carnitine for transport to mitochondria.

Peroxisomes contain oxidative enzymes, such as catalase, D-amino acid oxidase, and uric acid oxidase.

Certain enzymes within the peroxisome, by using molecular oxygen, remove hydrogen atoms from specific organic substrates in an oxidative reaction, producing hydrogen peroxide (H2O2, itself toxic)

Catalase, another peroxisomal enzyme, uses this H2O2 to oxidize other substrates, including phenols, formic acid, formaldehyde, and alcohol, by means of the peroxidation reaction, thus eliminating the poisonous hydrogen peroxide.

This reaction is important in liver and kidney cells, where the peroxisomes detoxify various toxic substances that enter the blood. About 25% of the ethanol humans drink is oxidized to acetaldehyde in this way. In addition, when excess H2O2 accumulates in the cell, catalase converts it to H2O through this reaction

DETOXIFICATION OF REACTIVE OXYGEN SPECIES

LIPID SYNTHESIS IN PEROXISOMES• Plasmalogens are relatively rare in some tissues but form a significant fraction of the membranes in nervous tissue. Some

of the steps in plasmalogen biosynthesis are localized in peroxisomes, and some peroxisomal disorders impair plasmalogen biosynthesis.

• Cholesterol: There is now considerable evidence that peroxisomes not only have a role in cholesterol oxidation but also in cholesterol biosynthesis.

Acetyl CoA Acetoacetyl CoATHIOLASE

Mevalonate Mevalonate-5-PhosphateMEVALONATE

KINASE

3-Hydroxy-3-methylglutaryl CoA

HMG REDUCTASE

Initiation steps in cholesterol synthesis

• Bile Acids: Peroxisomes play an important role in the biosynthesis of bile acids because a peroxisomal β-oxidation step is required for the formation of the mature C24-bile acids from C27-bile acid intermediates. In addition, de novo synthesized bile acids are conjugated within the peroxisome.

CHOLESTEROL

C27 Bile acid intermediates

C24 Bile acid formed by peroxisomal β-oxidation of

the side chain

GLYOXYLATE CYCLE IN PEROXISOMES (occurs in plants)

• Plants are capable of synthesizing carbohydrates from fatty acids via the glyoxylate cycle, which is a variant of the citric acid cycle.

• The Glyoxylate cycle provides the means to convert C2-units to C4-precursors for biosynthesis, allowing growth on fatty acids and C2-compounds.

• The operation of the Glyoxylate cycle requires transport of several intermediates across the peroxisomal membrane.

Glyoxysome reactions

PHOTORESPIRATION IN PEROXISOMESPeroxisomes play an important role by allowing most of the carbon in glycolate to be recovered and utilized.

GLYCOSOMES OF KINETOPLASTIDS The glycosome is a membrane-enclosed organelle that contains the glycolytic enzymes.

Found in a few species of protozoa including the Kinetoplastida which included the suborders Trypanosomatina and Bodonina, and Leishmania.

The organelle is bounded by a single membrane and contains a dense proteinaceous matrix. It is believed to have evolved from the peroxisome.

There has been a variety of evidence found biochemically to give evidence that glycosomes are present in cells. In the organelle that is assumed to be a glycosome, numerous proteins are found. These include glycogen synthase, phosphorylase, and branching and de-branching enzymes for glycogen. All of these are regulatory enzymes that are needed in glycogen synthesis.

SOME OTHER FUNCTIONS OF PEROXISOMES• The enzymes in peroxisomes break down long chain fatty acids by the process of oxidation. If allowed to accumulate these

fatty acids can damage structures such as the myelin ‘insulation’ sheath surrounding nerve fibers in the brain.

• In normal human hepatocytes, the intermediary-metabolic enzyme alanine-glyoxylate aminotransferase (AGT) is located within the peroxisomes. This protein is involved in preventing excess quantities of the chemical ‘oxalate’ from building up. A type of kidney stone is produced when oxalate joins with calcium to produce calcium oxalate. The proper functioning of this enzyme is therefore important.

• One of the enzymes found in peroxisomes from fireflies is called luciferase. This helps some males produce a bright flash of green/yellow light to attract females. The duration of the flash and the interval between the flashes is species specific and easily seen by females flying at night. In some species the female will flash in reply.

• A rare but fatal disorder of peroxisome molecular biology is Zellweger Syndrome. It is an inherited condition in which peroxisomal enzymes produced in the cytoplasm are unable to cross the membrane barrier and enter the matrix of the peroxisome. In this condition peroxisomes are present but only as ‘ghost’ or empty organelles.

ISOLATION OF PEROXISOMESTissue culture is homogenised. Kidney cells and hepatocytes contain large peroxisomes as compared to those found in fibroblasts or muscle cells. Isolated peroxisomes can be used to study fatty acid oxidation, amino acid metabolism lipid synthesis etc.

Serial centrifugations at 1000g, 2000g and 25000g remove cell debris, nuclei, mitochondria and lipids to obtain a crude peroxisomal fraction (lysosomes, ER, peroxisomes, light mitochondria)

Density gradient ultra-centrifuge to obtain peroxisomal fraction at the bottom of the tube.

Degree of purification of peroxisomes can be evaluated by comparing concentrations of catalase (peroxisome marker) and cytochrome C oxidase (mitochondrial marker)

REFERENCES• http://oregonstate.edu/dept/biochem/hhmi/hhmiclasses/biochem/lectnoteskga/2kjan14lecturenotes.html

• http://www.ncbi.nlm.nih.gov/books/NBK9930/

• http://www.sciencedirect.com/science/article/pii/S0167488906002758

• http://watcut.uwaterloo.ca/webnotes/Metabolism/fatGlyoxylateCycle.html

• http://bscb.org/learning-resources/softcell-e-learning/peroxisome/

• https://www.sigmaaldrich.com/content/dam/sigma-aldrich/docs/Sigma/Bulletin/perox1bul.pdf

• The Cell, Cooper

• Lehninger

• Wikipedia