Peroxisomes are membrane-bound organelles in most eukaryotic cells, primarily involved in lipid metabolism and the conversion of reactive oxygen species such as hydrogen peroxide into safer molecules like water and oxygen.
Fats are convenient energy storage molecules due to their high energy density. The number of ATP released from the oxidation of one gram of fat is much higher than that derived from carbohydrates or proteins. Lipids are also extremely useful molecules for the creation of membrane-bound subcompartments within cells or for delineating the cytoplasm from the extracellular space. Their lipophilic biochemistry, however, makes them difficult to metabolize within an aqueous cellular environment. Peroxisomes are structures where the metabolism of these hydrophobic molecules occurs.
Structure of Peroxisomes
Peroxisomes are organelles that can vary in shape, size and number depending on the energy needs of the cell. In yeast cells, a carbohydrate-rich growth medium shrinks peroxisomes. On the other hand, the presence of toxins or a lipid-rich diet can increase their number and size.
These organelles are made of a phospholipid bilayer with many membrane-bound proteins – especially those that act as protein transporters and translocators. The enzymes involved in detoxification and lipid metabolism are synthesized on free ribosomes in the cytoplasm and selectively imported into peroxisomes, making them more similar to mitochondria and chloroplasts when compared to lysosomes that bud off from the endoplasmic reticulum (ER). However, there is also some evidence linking ER-mediated protein synthesis to the enzymes present in peroxisomes.
Enzymes and proteins destined for the peroxisome usually contain one of two signal sequences. That is, there are short stretches of a few amino acids that determine the subcellular location of the protein. The more common signal sequence is called the Peroxisome Targeting Sequence 1 (PTS1), which consists of a amino acid trimer. Proteins containing PTS1 signal sequence have a serine residue followed by a lysine and then a leucine residue in their carboxy-terminal end. A large proportion of peroxisomal proteins have this signal sequence. For PTS1 to function optimally, amino acid sequences upstream of this trimer are also necessary. Some reports suggest that the C-terminal sequence should ideally be seen as a stretch of 20 amino acids that are necessary for the recognition of the protein by the peroxisomal transporter and translocator molecules.
Alternatively, a peroxisomal protein could also have an N-terminal signal sequence consisting of 9 amino acids. This sequence is made of two dimers separated by a stretch of 5 amino acids. The first dimer is made of arginine and leucine, while the second dimer is made of histidine and leucine. This signal sequence is represented using the single letter amino acid code as RLx5HL.
There is some evidence that there are other internal sequences that target proteins for import into the peroxisome that have not yet been characterized. Peroxisomes also contain some enzymes at very high concentrations, occasionally appearing to have a crystalloid core.
The phospholipids of the peroxisome are mostly synthesized in the smooth ER. As a peroxisome grows in size due to the ingress of proteins and lipids, it can divide into 2 organelles.
Comparison Between Peroxisomes and Other Organelles
Peroxisomes have some structural similarities with different organelles within the cell. Initially, it was difficult to even distinguish lysosomes from peroxisomes through microscopic examination alone. Thereafter, differential centrifugation revealed that these two subcellular structures had different compositions. Their protein and lipid components are distinct and they contain very different enzymes. Specifically, peroxisomes contain catalase to detoxify the hydrogen peroxide generated from the beta-oxidation of fats. Another major different is that lysosomal proteins are synthesized in the rough ER and vesicles that contain appropriate enzymes bud off to form the lysosome.
Peroxisomes share some similarities with mitochondria and chloroplasts. Most of the proteins of these organelles are translated on free ribosomes in the cytoplasm. However, unlike mitochondria and chloroplasts, peroxisomes contain no genetic material or translation machinery, therefore their entire proteome comes through import from the cytoplasm. In addition, a single lipid bilayer membrane forms peroxisomes, in contrast to the double membranous structures of mitochondria and chloroplasts.
Functions of Peroxisomes
Peroxisomes derive their name from their use of molecular oxygen for metabolic processes. These organelles are largely associated with lipid metabolism and the processing of reactive oxygen species. Within lipid metabolism, peroxisomes mostly deal with β–oxidation of fatty acids, the mobilization of lipid stores in seeds, cholesterol biosynthesis and steroid hormone synthesis.
The main reason for the high energy density of fats is the low proportion of oxygen atoms in every fatty acid molecule. For instance, palmitic acid, a fatty acid containing 16 carbon atoms and having a molecular mass of over 250 gms/mole, has only two oxygen atoms. While this makes lipids good storage molecules, they cannot be directly burnet as fuel or quickly catabolized in the cytoplasm through glycolysis. They need to be processed before they can be shunted into the mitochondria for complete oxidation through the citric acid cycle and oxidative phosphorylation.
When these molecules need to be oxidized to release ATP, they need to be first broken down into smaller molecules before they can be processed in the mitochondria. Within peroxisomes, long chain fatty acids are progressively broken down to generate acetyl coenzyme A (acetyl coA) in a process called β–oxidation. Acetyl coA then combines with oxaloacetate to form citrate. While most carbohydrates enter the citric acid cycle as a three-carbon molecule called pyruvate which is then decarboxylated to form acetyl coA, peroxisomal β–oxidation allows fatty acids to access the citric acid cycle directly.
One of the main byproducts of β–oxidation is hydrogen peroxide which can be harmful for the cell. This molecule is also carefully detoxified by the enzyme catalase within peroxisomes.
Peroxisomes in Plants
In plants, peroxisomes play important roles in seed germination and photosynthesis.
During seed germination, fat stores are mobilized for anabolic reactions that lead to the formation of carbohydrates. This is called the glyoxalate cycle and begins with β–oxidation and the generation of acetyl coA as well.
In leaves, peroxisomes prevent the loss of energy during photosynthetic carbon fixation through recycling the products of photorespiration. A crucial enzyme called Ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) is necessary for photosynthesis, catalyzing the carboxylation of ribulose-1,5-bisphosphate (RuBP). This is the central reaction for fixation of carbon dioxide to form organic molecules. However, RuBisCO, as the name suggests, can also oxygenate RuBP, using molecular oxygen, releasing carbon dioxide – in effect, reversing the net result of photosynthesis. This is particularly true when the plant is exposed to hot, dry environments and the stomata close in order to prevent transpiration.
When RuBisCO oxidizes RuBP, it generates a 2-carbon molecule called phosphoglycolate. This is captured by peroxisomes where it is oxidized to glycine. Thereafter, it is shuttled between the mitochondria and peroxisomes, undergoing a series of transformations before it is converted into a molecule of glycerate that can be imported into chloroplasts to participate in the Calvin cycle for photosynthesis.
Lipid Biosynthesis and Detoxification
In animal cells, peroxisomes are the sites for some amount of lipid biogenesis, especially of special phospholipids called plasmalogens that form the myelin sheath in nerve fibers. Peroxisomes are also necessary for the synthesis of bile salts. About 25% of the alcohol we consume is oxidized to acetaldehyde in these organelles. Their role in detoxifying and oxidizing a number of molecules, metabolic byproducts and drugs makes them a prominent part of kidney and liver cells.
Disorders Relating to Peroxisome Function
Disorders arising from deficient peroxisome function could arise from defects in peroxisome biogenesis, mutated peroxisomal enzymes, or non-functional transporters that recognize PTS1 and PTS2 in cytoplasmic proteins. The most severe of these are rare genetic disorders that result in impaired brain development and neuronal migration, along with myelin deficiency. Other organs affected include the skeletal system, liver, kidney, eyes, heart and lungs.
These disorders are usually caused by mutations in PEX genes, which are necessary for organelle biogenesis – from the formation of the subcellular membrane, to the recognition of cytoplasmic proteins and their import into the matrix of the organelle. For instance, PEX16 is involved in the synthesis of peroxisomal membranes, while PEX2 forms the translocation channel for the import of matrix proteins. PEX5, on the other hand is the receptor for recognizing the PTS1 signal sequence.
Defects in these proteins can cause the accumulation of long chain fatty acids in blood plasma or urine as well as the inappropriate presence of phospholipids like plasmalogens in red blood cells.
- Crystalloid – Similar to a crystal in appearance or properties.
- Differential Centrifugation – Technique for separating subcellular components based on their density and size, using repeated rounds of centrifugation at increasing speeds.
- Photorespiration – Respiratory process, especially in higher plants, that occurs in light and involves the uptake of oxygen and the release of carbon dioxide.
- Proteome – The complete set of proteins within a structure at a particular point in time. Can be used in reference to an entire organism, specific tissues with the body, individual cells or even subcellular components.
1. Which of these molecules is likely to be a fatty acid?
Answer to Question #1
B is correct. This is the formula for oleic acid, a fatty acid containing 18 carbon atoms, with one C:C double bond and a molecular weight of 282.47 gms/mole. This long chain fatty acid has only two atoms of oxygen. C6H12O6 is a molecule of glucose, a monosaccharide carbohydrate. C4H7NO4 and C5H9NO4 are molecules are aspartic acid and glutamic acid – naturally occurring amino acids. One of the hallmarks of a fatty acid is the low proportion of oxygen atoms in the molecule.
2. What is the role of peroxisomes in photosynthesis?
A. Increase the efficiency of carbon fixation
B. Mobilize fat stores for powering the energy-requiring steps of photosynthesis
C. Detoxify the hydrogen peroxide generated during β-oxidation of fats
D. All of the above
Answer to Question #2
A is correct. Peroxisomes in the stromal cells of leaves increase the efficiency of carbon fixation by reversing the oxidizing effect of RuBisCO. While peroxisomes do play a role in mobilizing fat stores (especially during seed germination) and detoxifying hydrogen peroxide, these are not directly relevant in the process of photosynthesis.
3. Why do many peroxisomal disorders result in deficient brain function?
A. Peroxisomes in the brain maintain the blood brain barrier that prevents the ingress of toxins into the central nervous system
B. Peroxisomes generate important phospholipids needed for neural activity
C. Peroxisome disorders lead to decreased liver function which affects the brain
D. All of the above
Answer to Question #3
B is correct. One of the main roles for peroxisomes in the nervous system is the generation of glycerophospholipids called plasmalogens. These lipids make up a large proportion of the lipids present in the central and peripheral nervous systems, especially within myelin sheaths. Though there is some ongoing work on the role of peroxisomes in the blood brain barrier, it has not been fully understood. Similarly, it can be argued that all the major organs of the body such as the liver and brain can affect each other. However, the proximal cause of deficient brain function is due to the lack of specific phospholipids that are synthesized in the peroxisomes present in nerve tissue.