Biochemistry-Cellular

Question 1

Describe regulation of the cell cycle

Answer 1

Checkpoints control transitions between phases in the cel cycle. This process is regulated by cyclines, cyclin-dependent kinases (CDKs), and tumor suppressors.

Question 2

What is included in M phase?

Answer 2

mitosis (prophase, prometaphase, metaphase, anaphase, and telophase) and cytokinesis

Question 3

What are the phases of the cell cycle?

Answer 3

M - G₁ - S - G₂ -M

Question 4

Note that CDKs are constitutive and active,

Cyclins are regulatory proteins that control cell cycle events; are ohase specific, and activate CDKs

Cyclin-CDK complexes phosphorylate other proteins to coordinate cell cycle progression

Question 5

What normally inhibits G1 to S progression?

Answer 5

p53 and hypophosphorylated Rb (mutations in these genes can result in unrestrained cell growth (e.g. Li- Fraumeni syndrome)

Question 6

What are the main cell types?

Answer 6

Permanent (remain in G_o phase, regenerate from stem cell; neurons, skeletal and cardiac muscle; RBCs)

Stable (enter G1 when stimulated; hepatocytes, lymphocytes)

Labile (Never go to Go, divide rapidly with a short G₁; most affected by chemo; bone marrow, gut epithelium, skin, germ cells hair)

Question 7

What is the rough ER?

Answer 7

the site of synthesis of secretory (excreted) proteins and of N-linked oligosaccharide addition to many proteins

Nissl bodies (RER in neurons) synthesize peptide neurotransmitters for secretion

Question 8

What does the smooth ER do?

Answer 8

site of steroid synthesis and detox of drugs and poisons (lacks surface ribosomes)

Liver hepatocytes and steroid hormone producing cells of the adrenal cortex and gonads are rich in SER

Question 9

Describe cell trafficking

Answer 9

The golgi is the distribution center for proteins and lipids from the ER to the vesicles and plasma membrane. The golgi modified N-oligosacchardies on asparagine, adds O-oligosacchardies on serine and threonine, and adds mannose-6-phosphate to proteins for trafficking to lysosomes

Endosomes are the sorting centers for materials from outside the cells or from the SGolgi, sending it to lysosomes for destruction or back to the membrane/Golgi for further use

Question 10

What is I disease?

Answer 10

(inclusion cell disease)- inherited lysosomal storage disorder caused by a defect in N-acetylglucosaminyl-1-phosphotransferase that results in failure of the Golgi to phosphorylate mannose residues (i.e. decreased mannose-6-phosphate) on glycoproteins. This results in proteins that are secreted extracellularly rather than delivered to lysosomes.

Question 11

How does I disease present?

Answer 11

coarse facial features, clouded corneas, restricted joint movement, and high plasma levels of lysosomal enzymes

Often fatal in childhood

Question 12

What is a signal recognition particle?

Answer 12

Abundant, cytosolic ribonucleoprotein that traffics proteins from the ribosome to the RER. Absent or dysfunctional SRP causes proteins to accumulate in the cytosol

Question 13

What are some major vesicular trafficking proteins?

Answer 13

COP1: Golgi to golgi (retrograde) or cis-Golgi to ER

COP2: ER to cis-Golgi (anterograde)

Clathrin: trans-golgi to lysosomes and plasma membrane to endosomes (receptor mediated endocytosis)

Question 14

What is the role of peroxisomes?

Answer 14

Membrane-enclosed organells involved in the catabolism of very-long-chain fatty acids, branched-chain FAs, and AAs

Question 15

What is the role of proteasomes?

Answer 15

These are barrel-shaped protein complexes that degrade damaged or ubiquitin-tagged proteins (defects in this system have been implicated in Parkinson disease)

Question 16

What are the main cytoskeleton components?

Answer 16

Microfilaments (actin; muscle contraction, cytokinesis)

Intermediate filaments (e.g. vimentin, GFAP, desmines, cytokeratin, lamins, neurofilaments; maintain cell structure)

Microtubules (e.g. cilia, flagella, mitotic spindle, neuronal trafficking; movement, and cell division)

Question 17

What body part does a vimentin stain ID? Desmins? Cytokeratin?

Answer 17

Vimentin- Connective tissue

Desmin- Muscle

Cytokeratin- Epithelial cells

Question 18

What body part does a GFAP stain ID? Neurofilaments?

Answer 18

GFAP- Neuroglia

Neurofilaments- neurons

Question 19

Describe the structure of microtubules

Answer 19

cylindrical structure composed of a helical array of polymerized heterodimers of a- and b-tubulin. Each dimer has 2 GTP bound.

Microtubules are incorporated into flaggella, cilia, mitotic spindles

Question 20

Anterograde transport along microtubules is accomplished via ______. Retrograde?

Answer 20

Anterograde- kinesin

Retro- dynein

Question 21

What drugs act upon microtubules?

Answer 21

Microtubules Get Constructed Very Poorly

Mebendazole (antihelminthic)

Griseofulvin (antifungal)

Colchicine (antigout)

Vincristine/Vinblastine

Paclitaxel

Question 22

What is the structure of cilia?

Answer 22

9+2 arrangement of microtubule doubles with axonemal dynein, an ATPase that links peripheral 9 doubles and causes bending of cilium by sliding

Question 23

What is Kartagener syndrome (primary ciliary dyskinesia)?

Answer 23

immotile cilia due to a dynein arm defect resulting in male and female infertility due to immotile sperm and dysfunctional fallopian tube cilia.

Increased risk of ectopic pregnancy

Can also result in bronchiectasis, recurrent sinusitis, and situs inversus

Question 24

What is the composition of the plasma membrane?

Answer 24

asymmetric lipid bilayer containing cholesterol, phospholipids, spingolipids, glucolipids, and proteins

NOTE: Fungal membranes contain ergosterol

Question 25

Describe the NaKATPase

Answer 25

3Na+ go out of the cell (when the pump is phosphorylated), 2K+ go in (when the pump is dephosphorylated)

Question 26

What drugs block the NaKATPase?

Answer 26

Ouabain inhibits by binding to the K+ sight Cardiac glycosides (digoxin and digitoxin) directly inhibit, whihc leads to indirect inhibition of Na/Ca2+ exchange to increase intracellular Ca2+ leading to increased cardiac contractility

Question 27

What are the types of collagen?

Answer 27

I-IV

Question 28

Describe type I collagen

Answer 28

most common (90%)- found in bone (made by osteoblasts), skin, tendons, dentin, fascia, cornea, and is involved in late wound repair Decreased production in osteogenesis imperfecta type I

Question 29

Describe type II collagen

Answer 29

found in cartilage (including hyaline), vitreous body, and nucleus pulposus

Question 30

Describe type III collagen

Answer 30

found in reticulin-skin, blood vessels, uterus, fetal tissue, and granulation tissue Type III is deficient in the uncommon, vascular type of Ehlers-Danlos

Question 31

Describe type IV collagen

Answer 31

Found in basement membrane, basal lamina, and the lens defective in Alport syndrome, and targeted by Abs in Goodpasture syndrome

Question 32

Describe the initial parts of collagen synthesis and structure

Answer 32

1. Synthesis (RER)-translation of collagen a chains (preprocollagen)-usually Glu-X-Y (X and Y are proline or lysine). Glycine content best reflects collagen synthesis (collagen is 1/3 glycine) 2) Hydroxylation of specific proline and lysine residues (requires vitC; deficiency= scurvy)

Question 33

Describe the parts 3 and 4 of collagen synthesis and structure

Answer 33

3) Glycosylation of pro-a-chain hydroxylysine residues and the formation of procollagen via hydrogen and disulfide bonds (triple helix of 3 collagen a chains); Problems forming triple helix= osteogenesis imperfecta 4) Exocytosis of procollagen from fibroblast into extracellular space

Question 34

Describe the parts 5 and 6 of collagen synthesis and structure

Answer 34

5) Proteolytic processing-cleavage of disulfide rich terminal regions of procollagen, transforming it into insoluble tropocollagen 6) Cross-linking: Reinforcement of many staggered tropocollagen molecules by covalent lysine-hydroxylysine cross-linkage (by copper-containing lysyl oxidase) to make collagen fibrils; problems with cross-linking= Ehlers-Danlos or Menkes disease

Question 35

Describe osteogenesis imperfecta

Answer 35

Genetic bone disorder caused by defects in collagen processing. Manifests with: mutliple fractures with minimal trauma blue sclera due to the translucency of the CT over the choroidal veins hearing loss (abnormal ossicles) dental imperfections due to a lack of dentin

Question 36

What is Ehlers Danlos syndrome?

Answer 36

Disease of faulty collagen syntheis causing hyperextensible skin, tendency to bleed, and hypermobile joints There are multiple types and inheritance and severity may vary (can be AD or AR)

Question 37

What are some types of Ehlers Danlos syndrome?

Answer 37

Hypermobility (most common) Classical types (joint and skin problems)- caused by mutation in type V collagen Vascular type (vascular and organ rupture)-deficient type III collagen

Question 38

What is Menkes disease?

Answer 38

X-linked recessive CT disease caused by impaired copper absorption and transport due to a defective Menkes protein (ATP7a) leading to decreased activity of lysyl oxidase resulting in brittle, kinky hair, growth retardation, and hypotonia

Question 39

What is elastin?

Answer 39

stretchy protein within skin, lungs, large, arteries, elastic ligaments, vocal cords, and ligamenta flava

Question 40

What is the composition of elastin?

Answer 40

rich is nonhydroxylated proline, glycine, and lysine residues

Question 41

Elastin is normally broken down by \_\_\_\_\_\_\_

Answer 41

elastase (which is inhibited by a1-antitrypsin

Question 42

What causes Marfan syndrome?

Answer 42

defct in fibrillin, a glycoprotein that forms a sheath around elastin

Question 43

What causes wrinkling of skin with age?

Answer 43

decreased collagen and elastin production