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Flashcards in FA - Biochemistry - Cellular Deck (92):
0

What characterizes CDKs?

Constitutive and inactive.

1

Which are the regulators of cell cycle phases?

1. Cyclins
2. CDKs
3. Cyclin-CDK complexes
4. Tumor suppressors

2

What are the cyclins?

1. Regulatory proteins that control cell cycle events.
2. PHASE SPECIFIC.
3. ACTIVATE CDKs.

3

Regulation of the cell cycle - Tumor suppressors

p53 induces p21 ==> INHIBITION OF CDKs ==> HYPOphosphorylation (=ACTIVATION) of RB ==> Binds to + Inactivates E2F ==> INHIBITION OF G1-S phase progression.

4

What are the 3 cell types regarding cell division?

1. Permanent --> Remain G0 - regenerate from stem cells.
2. Stable (quiescent) --> Enter G1 from G0 when stimulated.
3. Labile --> Never go to G0, divide rapidly with a short G1. Most affected by chemotherapy.

5

Mention some permanent cells?

1. Neurons
2. Skeletal muscle
3. Cardiac muscle
4. RBCs

6

Mention some stable cells?

1. Hepatocytes
2. Lymphocytes

7

Mention some labile cells.

1. Bone marrow
2. Gut epithelium
3. Skin
4. Hair follicles
5. Germ cells

8

What is the RER?

Site of synthesis of secretory (exported) proteins and of N-Linked oligosaccharide addition to many proteins.

9

What are the Nissl bodies?

RER in neurons --> Synthesize peptide neurotransmitters for secretion.

10

What are the free ribosomes?

Unattached to any membrane --> site of synthesis of cytosolic and organellar proteins.

11

Which cells are rich in RER?

1. Mucus-secreting goblet cells of the small intestine.
2. Antibody-secreting plasma cells.

12

What is the smooth endoplasmic reticulum?

1. Site of synthesis of steroids.
2. Site of detoxification of drugs and poisons.
==> Lacks surface ribosomes.

13

Which cells are rich in SER?

1. Hepatocytes
2. Steroid hormone-producing cells of the adrenal cortex and gonads.

14

What is the role of the Golgi?

1. Distribution center for proteins and lipids from the ER to the vesicles and plasma membrane.
2. Modifies N-oligosaccharides on asparagine.
3. Adds O-oligosaccharides on serine and threonine.
4. Adds mannose-6-phosphate to proteins for trafficking to lysosomes.

15

What are the endosomes?

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.

16

What happens in I-cell disease (inclusion cell disease/ mucolipidosis type II)?

1. Inherited lysosomal storage disorder.
2. Defect in N-acetylglucosaminyl-1-phosphotransferase.
3. Failure of Golgi to phosphorylate mannose residues (i.e., DOWN mannose-6-phosphate) on glycoproteins.
4. Proteins are secreted extracellularly rather than delivered to lysosomes.

17

What are the features of I-cell disease?

1. Coarse facial features
2. Clouded corneas
3. Restricted joint movement
4. High plasma levels of lysosomal enzymes
--> Often FATAL in childhood.

18

What is the SRP (signal recognition particle)?

1. Abundant, cytosolic ribonucleoprotein that traffics proteins from the ribosome to the RER.
2. Absent or dysfunctional SRP --> Proteins accumulate in the cytosol.

19

Mention 3 important vesicular trafficking proteins?

1. COP I
2. COP II
3. Clathrin

20

What is the role of COP I?

Golgi --> Golgi (RETROGRADE)
cis-Golgi --> ER.

21

What is the role of COP II?

cis-ER --> Golgi (ANTEROGRADE).

22

What is the role of clathrin?

TransGolgi --> Lysosomes
Plasma membrane --> Endosomes (receptor-mediated endocytosis [e.g., LDL receptor activity]).

23

What is the role of peroxisome?

Membrane-enclosed organelle involved in CATABOLISM of:
1. Very-long-chain fatty acids (through beta-ox).
2. Branched-chain fatty acids.
3. Amino acids.
4. Ethanol.

24

What is the proteasome?

Barrel-shaped protein complex that degrades damaged or ubiquitin-tagged proteins.

25

In which condition have defects in the ubiquitin-proteasome system been implicated?

In some cases of Parkinson disease!!!

26

What happens during synthesis of collagen?

Translation of collagen α-chains (preprocollagen) - usually Gly-X-Y (X and Y are proline or lysine).

27

Which amino acid content best reflects collagen synthesis (RER)?

Glycine content (collagen is 1/3 glycine).

28

What happens during hydroxylation of collagen (RER)?

Hydroxylation of specific proline and lysine residues (requires vitC - deficiency --> Scurvy).

29

What happens during glycosylation (RER)?

Glycosylation of pro-alpha-chain hydroxylysine residues and formation of procollagen via hydrogen and disulfide bonds (triple helix of 3 collagen alpha chains).

30

In which condition do we have problems forming triple helix?

In OSTEOGENESIS IMPERFECTA.

31

What follows glycosylation of collagen?

Exocytosis of procollagen into extracellular space.

32

What happens to collagen outside the cell?

1. Proteolytic processing
2. Cross-linking

33

What happens during proteolytic processing?

Cleavage of disulfide-rich terminal regions of procollagen, transforming it into insoluble tropocollagen.

34

What happens during cross-linking of collagen?

Reinforcement of many staggered tropocollagen molecules by covalent lysine-hydroxylysine cross-linkage (by Cu-containing lysyl oxidase) to make collagen fibrils.

35

In which 2 conditions do we have problems with cross-linking of collagen?

1. Ehlers-Danlos.
2. MENKES disease.

36

What happens in osteogenesis imperfecta?

Genetic bone disorder (brittle bone disease) caused by a variety of gene defects (MC COL1A1 + COL1A2).
--> May be confused with child abuse.

37

What is the MC form of osteogenesis imperfecta (OI)?

AD - With decr. production of otherwise normal type I collagen.

38

Mention some important OI manifestations?

1. Multiple fractures with minimal trauma - may occur during the birth process.
2. Blue sclerae due to translucency of the connective tissue over the choroidal veins.
3. Hearing loss (abnormal ossicles)
4. Some forms have TOOTH abnormalities, including OPALESCENT TEETH that wear easily due to LACK OF DENTIN (DENTINOGENESIS IMPERFECTA).

39

What happens in EDS?

Faulty collagen synthesis causing:
1. Hyperextensible skin.
2. Tendency to bleed (easy bruising).
3. Hypermobile joints.

40

How many types of EDS exist?

6+

41

Mention some important complications of EDS?

1. Joint dislocation
2. Berry aneurysm
3. Aortic aneurysms
4. Organ rupture

42

What is the MC type of EDS?

Hypermobility type (joint instability).

43

What happens in classical type of EDS?

Joint and skin symptoms --> Caused by mutation in type V collagen.

44

What happens in vascular type of EDS?

Vascular and organ rupture --> Deficient type III collagen.

45

What happens in Menkes disease?

XR ==> Connective tissue disease caused by impaired Cu absorption and transport due to DEFECTIVE MENKES PROTEIN (ATP7A).

46

What are the complications of Menkes disease?

Decr. activity of lysyl oxidase (Cu is a necessary cofactor).
==> Results in:
1. Brittle, "kinky" hair.
2. Growth retardation.
3. Hypotonia.

47

Where do we find elastin?

1. Skin
2. Lungs
3. Large arteries
4. Elastic ligaments
5. Vocal cords
6. Ligamenta flava (connect vertebrae --> relaxed + stretched formations).

48

In which amino acids is elastin rich?

1. NON hydroxylated proline.
2. Glycine.
3. Lysine.
residues.

49

Intra- or extracellularly does cross-linking of elastin take place?

Extracellularly and gives elastin its elastic properties.

50

Which enzyme brokes down elastin?

Elastase --> Normally inhibited by alpha-1 antitrypsin.

51

What happens in Marfan?

Defect in fibrillin --> Glycoprotein that forms a sheath around elastin.

52

What is the basis of wrinkles of aging?

Due to decr. collagen + elastin production.

53

What is basically a microtubule?

Cylindrical outer structure composed of a helical array of polymerized heterodimers of α- and β-tubulin.
--> Each dimer has 2 GTP bound.

54

Where are the microtubules incorporated?

1. Flagella
2. Cilia
3. Mitotic spindles
Grows slowly, collapses quickly.
--> Also involved in slow axoplasmic transport in neurons.

55

What are the molecular motor proteins?

Transport cellular cargo toward opposite ends of microtubule tracks.

56

Mention 2 examples of molecular motor proteins.

1. Dynein
2. Kinesin

57

What is the role of dynein?

Retrograde to microtubule (+ --> -).

58

What is the role of kinesin?

Anterograde to microtubule (- --> +).

59

Mention some drugs that act on microtubules.

Microtubules Get Constructed Very Poorly.

Mebendazole (anti-helminthic)
Griseofulvin (anti-fungal)
Colchicine (anti-gout)
Vincristine/Vinblastine (anti-cancer)
Paclitaxel (anti-cancer)

60

What is the cilia structure?

1. 9+2 arrangement of microtubule doublets.
2. The base of cilium below the cell membrane (called the BASAL BODY) consists of 9 microtubule triplets with NO CENTRAL MICROTUBULES.
3. Axonemal dynein --> ATPase that links peripheral 9 doublets and causes bending of cilium by differential sliding of doublets.
3.

61

What happens in Kartagener syndrome?

Immotile cilia due to a dynein arm defect.

62

What are the results of Kartagener syndrome?

1. Male/Female infertility --> Immotile sperm/dysfunctional fallopian tube cilia, respectively.
2. Incr. risk of ectopic pregnancy.
3. Can cause bronchiectasis
4. Recurrent sinusitis
5. Situs inversus (dextrocardia on CXR)

63

What are the cytoskeletal elements?

1. Actin and myosin
2. Microtubule
3. Intermediate filaments

64

What are the actins and myosins?

Actins --> Long, structural polymers.
Myosins --> Dimeric, ATP-driven motor proteins that move along actins.

65

What is the function of microtubules?

1. Movement - Cilia, flagella, mitotic spindle, axonal trafficking, centrioles.
2. Cell division.

66

What is the role of intermediate filaments?

MAINTAIN CELL STRUCTURE:
1. Vimentin
2. Desmin
3. Cytokeratin
4. Lamins
5. Glial fibrillary proteins (GFAP)
6. Neurofilaments

67

For what cell type does vimentin stain?

MESENCHYMAL TISSUE:
1. Fibroblasts.
2. Endothelial cells.
3. Macrophages.

68

For what cell type does desmin stain?

Muscle

69

For what cell type does cytokeratin stain?

Epithelial cells

70

For what cell types does GFAP stain?

NeuroGlia:
1. Astrocytes.
2. Schwann cells.
3. Oligodendroglia.

71

For what cell type does neurofilaments stain?

Neurons.

72

Mention 2 substances that inhibit Na-K ATPase?

1. Ouabain --> Binds to K site.
2. Digoxin --> Directly inhibits the Na-K ATPase --> Indirect inhibition of Na-Ca exchange --> UP Ca --> UP cardiac contractility.

73

Collagen - General features:

1. Most ABUNDANT protein in the human body.
2. Extensively MODIFIED BY POST-TRANSLATIONAL MODIFICATION.
3. Organizes + strengthens extracellular matrix.

74

What is the MC type of collagen?

Type I --> 90%
1. Bone (made by osteoblasts).
2. Skin
3. Tendon
4. Dentin
5. Fascia
6. Cornea
7. Late wound repair

75

What does type II collagen involve?

1. Cartilage (including hyaline)
2. Vitreous body
3. Nucleus pulposus

76

What does type III collagen include?

Reticulin:
1. Skin.
2. Blood vessels.
3. Uterus.
4. Fetal tissue.
5. Granulation tissue.

77

What does type IV collagen involve?

1. Basement mebrane
2. Basal lamina
3. Lens

78

What is the clinical correlation for type IV collagen?

1. Defective in Alport syndrome
2. Targeted by autoantibodies in Goodpasture syndrome

79

Type I collagen - Decr. production in ...?

OSTEOGENESIS IMPERFECTA.

80

Type III collagen - Deficient in the UNCOMMON ...?

VASCULAR TYPE OF EDS (type III).

81

M phase (SHORTEST PHASE) of the cell cycle include:

1. Mitosis.
2. Cytokinesis (=cytoplasm splits in 2).

82

G1 and G0 duration?

VARIABLE.

83

Regulation of the cell cycle - Cyclin-CDK complexes:

Phosphorylate other proteins to coordinate cell cycle progression ==> Must be activated + inactivated at appropriate times for cell cycle to progress.

84

I-cell disease - Which enzyme is deficient?

N-acetylglucosaminyl-1-phosphotransferase.

85

Cytoskeletal elements:

A network of protein fibers within the cytoplasm that supports:
1. Cell structure.
2. Cell + Organelle movement.
3. Cell division.

86

3 TYPES OF FILAMENTS:

1. Microfilaments.
2. Intermediate filaments.
3. Microtubules.

87

Microfilaments - Predominant function:

1. Muscle contraction.
2. Cytokinesis.

88

Microfilaments - Examples:

1. Actin.
2. Microvilli.

89

Collagen synthesis - 6 steps:

1. Synthesis.
2. Hydroxylation.
3. Glycosylation.
4. Exocytosis.
5. Proteolytic processing.
6. Cross-linking.

90

EDS - Inheritance?

VARIABLE - AD or AR.

91

Menkes disease - Inheritance:

XR.