- Rough endoplasmic reticulum
- Site of synthesis of secretory (exported) proteins and of N-linked oligosaccharide addition to many proteins.
- Nissl bodies (RER in neurons)—synthesize peptide neurotransmitters for secretion.
- Free ribosome
- unattached to any membrane
- site of synthesis of cytosolic and organellar proteins.
- Mucus-secreting goblet cells of the small intestine and antibody-secreting plasma cells are rich in RER.
- Smooth endoplasmic reticulum
- Lacks surface ribosomes
- Site of steroid synthesis
- detoxification of drugs and poisons.
- Liver hepatocytes and steroid hormone– producing cells of the adrenal cortex and gonads are rich in SER.
- Cell trafficking
- Golgi is the distribution center for proteins and lipids from the ER to the vesicles and plasma membrane.
- Modifies N-oligosaccharides on asparagine.
- AddsO-oligosaccharides on serine and threonine.
- Adds mannose-6-phosphate to proteins for trafficking to lysosomes.
- Endosomes are sorting centers for material from outside the cell or from the Golgi, sending it to lysosomes for destruction or back to the membrane/Golgi for further use.
- I–cell disease (inclusion cell disease)—
- inheritedlysosomal storage disorder
- defect in phosphotransferase→failure of the Golgi to phosphorylate mannose residues (i.e.,↓mannose- 6-phosphate) on glycoproteins →proteins are secreted extracellularly rather than delivered to lysosomes.
- Results in coarse facial features, clouded corneas, restricted joint movement, and high plasma levels of lysosomal enzymes.
- Often fatal in childhood.
- Signal recognition particle (SRP)
- Abundant, cytosolic ribonucleoprotein thattraffics proteins from the ribosome to the RER.
- Absent or dysfunctional SRP→ proteins accumulate in the cytosol.
- Vesicular trafficking proteins
- COPI: Golgi →Golgi (retrograde); Golgi →ER.
- COPII: Golgi → Golgi (anterograde); ER → Golgi.
- Clathrin: trans-Golgi → lysosomes; plasma membrane → endosomes (receptormediatedendocytosis [e.g., LDL receptor activity]).
- Membrane-enclosed organelle involved in catabolism of very-long-chain fatty acids, branched-chain fatty acids, and amino acids.
- Barrel-shaped protein complex that degrades damaged or ubiquitin-tagged proteins.
- Defects in the ubiquitin-proteasome system have been implicated in some cases of Parkinson disease.
- Cylindrical structure composed of a helical array of polymerized heterodimers of α- andβ-tubulin.
- Each dimer has 2 GTP bound.
- Incorporated into flagella, cilia, mitotic spindles.
- Grows slowly, collapses quickly.
- Also involved in slow axoplasmic transport in neurons.
- Molecular motor proteins—transport cellular cargo toward opposite ends of microtubuletracks.
- Dynein = retrograde to microtubule (+→ -).
- Kinesin = anterograde to microtubule (- → +).
- Drugs that act on microtubules
- 9 + 2 arrangement of microtubules
- Axonemal dynein—ATPase links peripheral9 doublets and causes bending of cilium by differential sliding of doublets.
- Kartagener syndrome (1° ciliary dyskinesia)—
- immotile cilia due to a dynein arm defect.
- Results in male and female infertility due to immotile sperm and dysfunctional fallopian tube cilia, respectively;
- ↑ risk of ectopic pregnancy.
- Can cause bronchiectasis, recurrent sinusitis, and situsinversus (e.g., dextrocardia on CXR).
- Cytoskeletal elements
- Actin and myosin
- Muscle contraction, microvilli, cytokinesis, adherens junctions.
- Actins are long, structural polymers.
- Myosins are dimeric, ATP-driven motor proteins that move along actins.
- Cilia, flagella, mitotic spindle, axonal trafficking, centrioles.
- Vimentin, desmin, cytokeratin, lamins, glial fibrillary acid proteins (GFAP),Neurofilaments
- Plasma membrane composition
- Asymmetric lipid bilayer.
- Contains cholesterol, phospholipids, sphingolipids, glycolipids, and proteins.
- Fungal membranes contain ergosterol.
- Immunohistochemical stains for intermediate filaments
- Vimentin– Connective tissue
- DesMin – Muscle
- Cytokeratin -Epithelial cells
- Neurofilaments -Neurons
- Sodium-potassium pump
- Na+-K+ ATPase is located in the plasma membrane with ATP site on cytosolic side.
- For each ATP consumed, 3 Na+ go out and 2 K+ come in.
- Ouabain inhibits by binding to K+ site.
- Cardiac glycosides (digoxin and digitoxin)
- directlyinhibit the Na+-K+ ATPase
- leads to indirect inhibition of Na+/ Ca2+ exchange→↑[Ca2+]i→cardiac contractility.
1. A couple has had fi ve children, all of who exhibit short stature, eyelid droop, and some degree of muscle weakness and hearing loss (some severe, some mild). The mother also has such problems, although at a mild level. The father has no symptoms. The mutation that afflicts the children most likely resides in DNA found in which intracellular organelle?
(D) Endoplasmic reticulum
7 The answer is A:
Mitochondria. The mother and children are experiencing the effects of a mitochondrial disorder. Eukaryotic cells actually have two genomes; one in the nucleus, and another in the mitochondria. The mitochondrial genome codes for a small number of proteins which are found in the mitochondria. In order to make these proteins the mitochondria also synthesize their own tRNA molecules. As only the mother transmits mitochondria to her children, mitochondrial diseases display a unique inheritance pattern. None of the other organelles listed, other than the nucleus, contain DNA, and these symptoms and inheritance pattern are not consistent with a mutation in nuclear DNA. The mitochondrial genome is 15,569 base pairs in size, encoding 37 genes. These genes include two different molecules of rRNA, 22 different tRNA molecules, and 13 polypeptides (seven subunits of NADH dehydrogenase, or complex I, three subunits of cytochrome c oxidase, or complex IV, two subunits of the proton translocating ATP synthase, and cytochrome b). There are multiple mitochondrial disorders associated with muscular dystrophy, including Kearns–Sayer syndrome (this case), Leigh syndrome (non-X-linked), Pearson syndrome, mitochondrial DNA depletion syndrome, and mitochondrial encephalomyopathy.
2. A 2-month-old infant with failure to thrive displays hepatomegaly, high levels of iron and copper in the blood, and vision problems. This child has difficulty in carrying out which of the following types of reactions?
(A) Oxidation of very long chain fatty acids
(B) Synthesis of unsaturated fatty acids
(C) Oxidation of acetyl-CoA
(D) Oxidation of glucose
(E) Synthesis of triacylgycerol
14 The answer is A:
Oxidation of very long chain fatty acids. The child has Zellweger’s syndrome, an absence of peroxisomal enzyme activity. Of the pathways listed as answers, only the oxidation of very long chain fatty acids s a peroxisomal function. Fatty acid synthesis occurs in the cytoplasm. Acetyl-CoA oxidation takes place in the mitochondria. Glucose oxidation is a combination of glycolysis (cytoplasm) and the TCA cycle (mitochondria). Triglyceride synthesis occurs in the cytoplasm.
3.Your patient with metabolic syndrome is in for a checkup. His HbA1C is 9.0 and his fasting triglycerides are 325 mg/dL. You prescribe pioglitazone (Actos) to better treat his diabetes, but nothing else specifi c for the high lipids. A month later, the fasting triglyceride levels have dropped to 155 mg/dL due to a direct activation of which of the following?
(A) AMP-activated protein kinase
12 The answer is B:
PPAR-g. Thiazolidinediones (TZDs), of which pioglitazone is a member bind to peroxisome proliferator activated receptor-γ (PPAR-γ) in the adipocyte and activate the synthesis and release of adiponectin, which acts on target cells to reduce blood glucose levels (by upregulating GLUT4 content of the membranes) and to reduce circulating triglyceride levels (through phosphorylation and inhibition of acetyl-CoA carboxylase 2, which relieves the inhibition of carnitinepalmitoyltransferase I). While adiponectin levels rise, which leads to a stimulation of the AMP-activated protein kinase, neither of those effects is due to a direct interaction with the TZD. LKB1, an upstream kinase responsible for activating the AMP-activated protein kinase, and leptin are not involved in the response to TZDs.
3. Zellweger syndrome is due to:
A. Deficiency of medium chain acyl CoA dehydrogenase
B. Deficiency of methyl malonyl CoA mutase
C. Absence of peroxisomes
D. Deficiency of vitamin B12
ANS:C. Zellweger syndrome is due to the absence of peroxisomes in all tissues. Very long chain fatty adds are not oxidized and accumulate in the blood and tissues. Sudden infant death syndrome is due to deficiency of medium chain acyl CoA dehydrogenase. Deficiency of methylmalonyl CoA mutase and vitamin B12 leads to methylmalonicadduria, which results in metabolic addosis.
4. Which one of the following statement is correct regarding cell organelles:
A. Isocitrate dehydrogenase enzyme is localized in the outer membrane of mitochondria
B. In eukaryotic cell rough endoplasmic reticulum is the major site of lipid synthesis
C. Golgi apparatus contain acid hydrolases
D. Peroxisomes contain the enzyme catalase
ANS:D. Isocitrate dehydrogenase enzyme is localized in the matrix of mitochondria. In eukaryotic cell, rough endoplasmic reticulum is the major site of protein synthesis and smooth endoplasmic reticulum is the major site of lipid synthesis. Lysosomes contain acid hydrolases that degrade proteins, nucleic acids, polysaccharides and lipids. These enzyme functions are specifically at the acidic pH. Peroxisomes contain the enzyme catalase, which decomposes hydrogen peroxide.
5. Pick out the correct statement regarding composition ot cytoskeleton of eukaryotic cells:
A. Cytoskeleton present on the plasma membrane
B. It is composed of microfilaments, microrubules and intermediate filaments
C. Vimentin, keratin and dermin are the microfilament proteins
D. In animal cell microtiibule organizing center is peroxisomes
ANS: B. Cytoskeleton present underneath the plasma membrane is composed of microfilaments, microtubules and intermediate filaments. Actin filaments are known as microfilaments. They are responsible for intracellular movements. Vimentin, keratin and dermin are the intermediate filament proteins; they provide mechanical strength to cells and tissues. Microtubules are composed of single type of globular protein called tub’ulin. Tubulin consists of two polypeptides a-tubulin and p-tubulin. They are important in maintaining cell shape, intracellular transport of organelles and the separation of chromosomes during mitosis. The major microtubule organizing center in animal cells is the centrosome.