Peroxisomes - Another Enzyme Package There are many ways that peroxisomes are similar to lysosomes.

They are small vesicles found around the cell. They have a single membrane that contains digestive enzymes for breaking down toxic materials in the cell. They differ from lysosomes in the type of enzyme they hold. Peroxisomes hold on to enzymes that require oxygen (oxidative enzymes). Lysosomes have enzymes that work in oxygen-poor areas and lower pH. Peroxisomes absorb nutrients that the cell has acquired. They are very well known for digesting fatty acids. They also play a part in the way organisms digest alcohol (ethanol). Because they do that job, you would expect liver cells to have more peroxisomes than most other cells in a human body. They also play a role in cholesterol synthesis and the digestion of amino acids. Creating Hydrogen Peroxide Peroxisomes work in a very specific way. Their enzymes attack complex molecules and break them down into smaller molecules. One of the byproducts of the digestion is hydrogen peroxide (H2O2). Peroxisomes have developed to a point where they are able to contain that hydrogen peroxide and break it down into water (H2O) and oxygen (O2). The water is harmless to the cell and the oxygen can be used in the next digestive reaction. Mysteries of the Peroxisome Peroxisomes have a single membrane that surrounds the digestive enzymes and dangerous byproducts of their work (hydrogen peroxide). The protein enzymes are usually created by lysosomes floating in the cell. They then insert the proteins into the peroxisome bubble. Peroxisomes continue to grow until they split in two. Where does the membrane come from? Scientists are still researching that answer. It may come from the endoplasmic reticulum, but it may be created in a way different from lysosomes.

http://www.ncbi.nlm.nih.gov/books/NBK26858/ Summary
Peroxisomes are specialized for carrying out oxidative reactions using molecular oxygen. They generate hydrogen peroxide, which they use for oxidative purposes destroying the excess by means of the catalase they contain. Peroxisomes also have an important role in the synthesis of specialized phospholipids required for nerve cell myelination. Like mitochondria and plastids, peroxisomes are thought to be selfreplicating organelles. Because they contain no DNA or ribosomes, however, they have to import their proteins from the cytosol. A specific sequence of three amino acids near the C terminus of many of these proteins functions as a peroxisomal import signal. The mechanism of protein import is distinct from that of mitochondria and chloroplasts, and oligomeric proteins can be transported into peroxisomes without unfolding.

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/L/Lysosomes.html

Peroxisomes
Peroxisomes are about the size of lysosomes (0.51.5 m) and like them are enclosed by a single membrane. They also resemble lysosomes in being filled with enzymes. However, peroxisomes bud off from the endoplasmic reticulum, not the Golgi apparatus (that is the source of lysosomes). The enzymes and other proteins destined for peroxisomes are synthesized in the cytosol. Each contains a peroxisomal targeting signal (PTS) that binds to a receptor molecule that takes the protein into the peroxisome and then returns for another load. Two peroxisomal targeting signals have been identified:

a 9-amino acid sequence at the N-terminal of the protein; a tripeptide at the C-terminal.

Each has its own receptor to take it to the peroxisome.

Some of the functions of the peroxisomes in the human liver:

Breakdown (by oxidation) of excess fatty acids. Breakdown of hydrogen peroxide (H2O2), a potentially dangerous product of fatty-acid oxidation. It is catalyzed by the enzyme catalase. [Link to further discussion] Participates in the synthesis of cholesterol. One of the enzymes involved, HMG-CoA reductase, is the target of the popular cholesterol-lowering "statins". Participates in the synthesis of bile acids. Participates in the synthesis of the lipids used to make myelin. Breakdown of excess purines (AMP, GMP) to uric acid.

Peroxisomes are also present in plant cells where they participate is such functions as

symbiotic nitrogen fixation photorespiration

Peroxisome Disorders A variety of rare inherited disorders of peroxisome function occur in humans.

Most involve mutant versions of one or another of the enzymes found within peroxisomes.

Example: X-linked adrenoleukodystrophy (X-ALD). This disorder results from a failure to metabolize fatty acids properly. One result is deterioration of the myelin sheaths of neurons. The disorder occurs in young boys because the gene is X-linked. An attempt to find an effective treatment was the subject of the 1992 film Lorenzo's Oil.

A few diseases result from failure to produce functional peroxisomes.

Example: Zellweger syndrome. This disorder results from the inheritance of two mutant genes for one of the receptors (PXR1) needed to import proteins into the peroxisome. Peroxisomes are also called microbodies.

http://www.youtube.com/watch?v=z0CJZ9ulAdo

http://www.ninds.nih.gov/disorders/zellweger/zellweger.htm What is Zellweger Syndrome?

Zellweger syndrome is one of a group of four related diseases called peroxisome biogenesis disorders (PBD). The diseases are caused by defects in any one of 13 genes, termed PEX genes, required for the normal formation and function of peroxisomes. The PBDs are divided into two groups: Zellweger spectrum disorders and Rhizomelic Chondrodysplasia Punctua spectrum. The Zellweger spectrum is comprised of three disorders that have considerable overlap of features. These include Zellweger syndrome (ZS, the most severe form), neonatal adrenoleukodystrophy (NALD), and Infantile Refsum disease (IRD, the least severe form). Peroxisomes are cell structures that break down toxic substances and synthesize lipids (fatty acids. oils, and waxes) that are necessary for cell function. Peroxisomes are required for normal brain development and function and the formation of myelin, the whitish substance that coats nerve fibers. They are also required for normal eye, liver, kidney, and bone functions. Zellweger spectrum disorders result from dysfunctional lipid metabolism, including the over-accumulation of very long-chain fatty acids and phytanic acid, and defects of bile acids and plasmalogens--specialized lipids found in cell membranes and myelin sheaths of nerve fibers. Symptoms of these disorders include an enlarged liver; characteristic facial features such as a high forehead, underdeveloped eyebrow ridges, and wide-set eyes; and neurological abnormalities such as mental retardation and seizures. Infants will Zellweger syndrome also lack muscle tone, sometimes to the point of being unable to move, and may not be able to suck or swallow. Some babies will be born with glaucoma, retinal degeneration, and impaired hearing. Jaundice and gastrointestinal bleeding also may occur.

Is there any treatment?

There is no cure for Zellweger syndrome, nor is there a standard course of treatment. Since the metabolic and neurological abnormalities that cause the symptoms of Zellweger syndrome are caused during fetal development, treatments to correct these abnormalities after birth are limited. Most treatments are symptomatic and supportive.

What is the prognosis?

The prognosis for infants with Zellweger syndrome is poor. Most infants do not survive past the first 6 months, and usually succumb to respiratory distress, gastrointestinal bleeding, or liver failure.

What research is being done?

The National Institute of Neurological Disorders and Stroke (NINDS), and other institutes of the National Institutes of Health (NIH), conduct research exploring the molecular and genetic basis of Zellweger syndrome and the other PBDs, and also support additional research through grants to major research institutions across the country. Much of this research focuses on finding better ways to prevent, treat, and ultimately cure disorders such as Zellweger syndrome.

http://ghr.nlm.nih.gov/condition/zellweger-spectrum

What is Zellweger spectrum?

The Zellweger spectrum is a group of conditions that have overlapping signs and symptoms and affect many parts of the body. This group of disorders includes Zellweger syndrome, neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease. These conditions were once thought to be distinct disorders but are now considered to be part of the same disease spectrum. Zellweger syndrome is the most severe form of the Zellweger spectrum, NALD is intermediate in severity, and infantile Refsum disease is the least severe form. In some cases, it can be difficult to distinguish between the three conditions that make up the Zellweger spectrum. Individuals with Zellweger syndrome develop signs and symptoms of the condition during the newborn period. These infants experience weak muscle tone (hypotonia), feeding problems, hearing loss, vision loss, and seizures. These problems are caused by the degeneration of myelin, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses. The part of the brain and spinal cord that contains myelin is called white matter. Destruction of the myelin (demyelination) leads to loss of white matter (leukodystrophy). Children with Zellweger syndrome also develop life-threatening problems in other organs and tissues, such as the liver, heart, and kidneys. They may have skeletal abnormalities, including a large space between the bones of the skull (fontanels) and characteristic bone spots known as chondrodysplasia punctata that can be seen with an x-ray. Affected individuals have distinctive facial features, including a flattened face, broad nasal bridge, and high forehead. Children with Zellweger syndrome typically do not survive beyond the first year of life. People with NALD or infantile Refsum disease have more variable features than those with Zellweger syndrome and usually do not develop signs and symptoms of the disease until late infancy or early childhood. They may have many of the features seen in more severely affected individuals; however, their condition typically progresses more slowly. Children with these less severe conditions often have hypotonia, vision problems, hearing loss, liver dysfunction, developmental delay, and some degree of intellectual disability. Most people with NALD survive into childhood, and those with infantile Refsum disease may reach adulthood. In rare cases, individuals at the mildest end of the Zellweger spectrum have developmental delay in childhood and hearing loss or vision problems beginning in adulthood.

How common is Zellweger spectrum?

The Zellweger spectrum is estimated to occur in 1 in 50,000 individuals.

What genes are related to Zellweger spectrum?

Mutations in 12 genes have been found to cause the Zellweger spectrum. These genes provide instructions for making a group of proteins known as peroxins, which are essential for the formation and normal functioning of cell structures called peroxisomes. Peroxisomes are sac-like compartments that contain enzymes needed to break down many different substances, including fatty acids and certain toxic compounds. They are

also important for the production of fats (lipids) used in digestion and in the nervous system. Peroxins assist in the formation (biogenesis) of peroxisomes by producing the membrane that separates the peroxisome from the rest of the cell and by importing enzymes into the peroxisome. Mutations in the genes that cause the Zellweger spectrum prevent peroxisomes from forming normally. Diseases that disrupt the formation of peroxisomes, including the Zellweger spectrum, are called peroxisome biogenesis disorders. If the production of peroxisomes is altered, these structures cannot perform their usual functions. The signs and symptoms of Zellweger syndrome are due to the absence of functional peroxisomes within cells. NALD and infantile Refsum disease are caused by mutations that allow some peroxisomes to form. Mutations in the PEX1 gene are the most common cause of the Zellweger spectrum and are found in nearly 70 percent of affected individuals. The other genes associated with the Zellweger spectrum each account for a smaller percentage of cases of this condition. Read more about the PEX1 gene. See a list of genes associated with Zellweger spectrum.

How do people inherit Zellweger spectrum?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. http://ulf.org/the-zellweger-spectrum http://www.ncbi.nlm.nih.gov/books/NBK9930/ http://www.britannica.com/EBchecked/topic/452457/peroxisome/