Материал: Kaplan USMLE-1 (2013) - Anatomy

Chapter i.

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Copyright Lippincott Williams & Wilkins. Used with permission.

Figure 1-1-4. Human corpus luteum of pregnancy

Functions ofSER

Detoxification Reactions

These are reactions that make compounds water-soluble so that they can be excreted. Two types of reactions that increase solubility are:

•Hydroxylation reactions-by way of hydroxylase complexes containing cytochrome P450, a flavoprotein, and a nonheme iron protein

•Conjugation reactions-the transfer of polar groups (i.e., glucuronic

acid) from the active carrier UDP-glucuronic acid to the toxic water­ insoluble molecule

Steroid Synthesis

Glycogen Degradation and Gluconeogenesis

Removal of the phosphate group from glucose-6-phosphate by the enzyme glu­ cose-6 phosphatase, an integral membrane protein of the SER. This controls the formation of free glucose from glycogen and via gluconeogenesis.

Reactions in Lipid Metabolism

Lipolysis begins in the SER with the release of a fatty acid from triglyceride. The SER is also the site where lipoprotein particles are assembled.

Sequestration and Release of Calcium Ions

In striated muscle the SER is known as the sarcoplasmic reticulum (SR). The sequestration and release of calcium ions takes place in the SR.

• Cell Biology and Epithelia

Note

Lysosomal enzymes breakdown sphingolipids and glycoproteins into soluble products.

Clinical Correlate

I-Cell Disease

Phosphorylation of mannose in glycoproteins targets proteins to lysosomes. Phosphate is added in a 2-step sequence of reactions that are catalyzed by N-acetylglucosamine-phosphotransferase and N-acetylglucosaminidases.

A deficiency in N-acetylglucosamine-phosphotransferase results in I-cell disease (mucolipidosis II), in which a whole family of enzymes is sent to the wrong destination. It is characterized by huge inclusion bodies in cells caused by the accumulation of undegraded glycoconjugates in lysosomes missing the hydrolases that normally degrade these macromolecules. The missing enzymes are found in the plasma and other body fluids, where they have normal levels of activity. The absence of the mannose-6-phosphate on the hydrolases results in their secretion rather than their incorporation into lysosomes.

The disease results in skeletal abnormalities, coarse features, restricted joint movements, and psychomotor retardation. Symptoms are generally noted at birth, and the life span is less than 10 years.

A somewhat less severe form of the disease with a later onset and potential survival into adulthood is called pseudo-Hurler polydystrophy.

There is no treatment for either disease, but prenatal diagnosis is available.

Clinical Correlate

Deficient breakdown of sphingolipids is cause of Gaucher, Niemann-Pick, and Tay-Sachs disease.

Lysosomes

Lysosomes are spherical membrane-enclosed organelles that are approximately 0.5 µm in diameter and contain enzymes required for intracellular digestion (Figure 1-1-7).

Lysosomes consist of 2 forms:

•Primarylysosomes have not yet acquired the materials to be digested. They are formed by budding from the trans side of the Golgi apparatus.

•Secondary lysosomes are formed by the fusion of the primary lysosome with the substrate to be degraded and have contents that are in various stages of degradation.

Lysosomes contain approximately 60 hydrolytic enzymes. These include nucle­ ases for degrading DNA and RNA, lipases for degrading lipids, glycosidases for degrading glycoconjugates (glycoproteins, proteoglycans, and glycolipids), prote­ ases and peptidases for degrading proteins, and a variety of phosphatases.

•All lysosomal enzymes are acid hydrolases, with optimal activity at a pH of approximately 5.0.

•The synthesis of the lysosomal hydrolases occurs in the RER; the hydro­ lases are transferred to the Golgi apparatus, where they are modified and packaged into lysosomes.