Oxidative enzymes are particularly important in liver cells (hepatocytes), where they perform a variety of detoxification processes. Peroxisomes in hepatocytes are responsible for detoxification of ingested alcohol by converting it to acetaldehyde. The -oxidation of fatty acids is also a major function of peroxisomes. In some cells, peroxisomal fatty-acid oxidation may equal that of mitochondria. The proteins contained in the peroxisome lumen and membrane are synthesized on cytoplasmic ribosomes and imported into the peroxisome. A protein destined for peroxisomes must have a peroxisomal targeting signal attached to its carboxy-terminus.
Although abundant in liver and kidney cells, peroxisomes are also found in most other cells. The number of peroxisomes present in a cell increases in response to diet, drugs, and hormonal stimulation. In most animals, but not humans, peroxisomes also contain urate oxidase (uricase), which often appears as a characteristic crystalloid inclusion (nucleoid).
Various human metabolic disorders are caused by the inability to import peroxisomal proteins into the organelle because of a faulty peroxisomal targeting signal or its receptor. Several severe disorders are associated with nonfunctional peroxisomes. In the most common inherited disease related to nonfunctional peroxisomes, Zellweger syndrome, which leads to early death, peroxisomes lose their ability to function because of a lack of necessary enzymes. The disorder is caused by a mutation in the gene encoding the receptor for the peroxisome targeting signal that does not recognize the signal Ser-Lys-Leu at the carboxyterminus of enzymes directed to peroxisomes. Therapies for peroxisomal disorders have been unsatisfactory to date.
Microtubules are nonbranching and rigid hollow tubes of protein that can rapidly disassemble in one location and reassemble in another. In general, they grow from the microtubule-organizing center located near the nucleus and extend toward the cell periphery. Microtubules create a system of connections within the cell, frequently compared with railroad tracks, along which vesicular movement occurs.
Microtubules are elongated polymeric structures composed of equal parts of -tubulin and -tubulin.
Microtubules measure 20 to 25 nm in diameter (Fig. 2.39). The wall of the microtubule is approximately 5 nm thick and consists of 13 circularly arrayed globular dimeric tubulin molecules. The tubulin dimer has a molecular weight of 110 kilodaltons (kDa) and is formed from an -tubulin and a -tubulin molecule, each with a molecular weight of 55 kDa (Fig. 2.40). The dimers polymerize in an end-to-end fashion, head to tail, with the molecule of one dimer bound to the
FIGURE 2.39 • Electron micrographs of microtubules. a. Micrograph showing microtubules (arrows) of the mitotic spindle in a dividing cell. On the right, the microtubules are attached to chromosomes. 30,000. b. Micrograph of microtubules (arrows) in the axon of a nerve cell. In both cells, the microtubules are seen in longitudinal profle. 30,000.
molecule of the next dimer in a repeating pattern. Longitudinal contacts between dimers link them into a linear structure called a protoflament. Axial periodicity seen along the 5-nm-diameter dimers corresponds to the length of the protein molecules. A small, 1-m segment of microtubule contains approximately 16,000 tubulin dimers. The arrangement of -tubulin and -tubulin molecules within the microtubule is visible in Figure 2.41.
Microtubules grow from -tubulin rings within the MTOC that serve as nucleation sites for each microtubule.