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Flashcards in Chapter 1 Deck (76):
1

SNP: function

single nucleotide polymophism: variants at single nucleotide position (adenine vs thymine)

2

CNV: Function

Copy number variations: large number of repeats in genome, 50% involve gene coding sequences

3

Nucleosome

147 base pairs wrapped around central core of histones

4

Histone acetylation function

open up chromatin and increase transcription

5

DNA Methylation

transcription silencing

6

DICER

DICER trims and processes primary microRNA

7

RISC

RNA induced silencing complex: multiprotein aggregate assocaites with mature ss microRNA to target mRNA for cleavage and repress translation

8

XIST

Long noncoding RNA transcribed from x chromsome: essential in physiologic X chromosome inactivation: gene silencing

9

Phosphotidylinositol

Inner leaflet of cell membrane, can be phosphorylated--> scaffold for intracelluar proteins, or hydrolized by phospholipase C generating second signals (Diacylglycerol and inositol triphosphate)

10

Phosphatidylserine

Inner leaflet of cell membrane, when flipped to extracellular surface cell undergoes apoptosis.

11

Phosphatidylserin role in clotting

cofactor for platelets in clotting

12

outerleaflet components of plasma membrane

Glycolipids: gangliosides: cell to cell interactions and cell matrix interaction.
Sphingomyelin

13

Glycosylphosphatidylinositol

anchors on extracellular face of membrane, helps with insertion of proteins into membrane

14

Molecules able to passively diffuse through membrane

small non polar molecules: O2 or CO2
Hydrophobic molecules (steroids or vit D)
Polar molacules <75 daltons (water ehtanol urea)

15

Channel proteins

create hydrophilic pores for rapid movement of hydrophilic solutes

16

Carrier proteins

Bind specific solute results in conformational changes and ligand transfered across membrane

17

Active transport

transport solutes across gradient using ATP. Pump sodium or chloride out of cell to maintain osmotic concentrations

18

Endocytosis mechanisms

1. Caveolae: plasma membrane invaginations
2.Clathrin: receptor mediated endocytosis

19

Calveolae mechanisms

potocytosis: cellular sipping thorugh internalization of calveolin with molecules or extracellular fluid.

20

Calveolae implications

1. folate delivery
2. regulate transmembrane singaling or cell adhesion via internalization of receptors and integrins

21

Clathrin mechanism

Pinocytosis: invagination of plasma membrane forming vesicles

Clathrin coated pits on plasma membrane pinches off to form clathrin coated vesicle with macromolecules and fluids in vesicle--> fuse with acidic early endosome--> discharge contents for digestion--> pass to lysosome

22

Receptor mediated endocytosis

Bind receptor localized in clathrin coated pits--> endocytose--> fuse with lysosome--> release contents into cytoplasm (LDL and transferrin specifically, which are resistant to lysosomes

23

Exocytosis

large molecules secreted out of cell through golgi synthesized secretory vessels that fuse with plasma membrane

24

Nucleolar organizing regions (NORs)

Nonmembrane bound structure forms aroudn chromsoomal loci of ribosomal RNA genes

25

List intermediate filaments (6)

Lamin A, B, C
Vimentin
Desmin
Neurofilaments
Flial fibrillary acidic protein
Cyotkeratins

26

Microfilament example

actin- important in cell shape and movement

27

Microtubules size

25nm thick

28

Microtubule functions

alpha and beta tubulin
Function: molecular motor, chromatin separation in mitosis, adapted to form motile cilia or flagella
examples: Kinesin, Dynein

29

Occluding junction examples (4)

Complexes composed of transmembrane proteins:
Claudin, occludin, zonulin, catenin

30

Desmosome

anchoring junctions
attach cell to other cells and ECM

31

Spot desmosomes

Macula adherens
Desmoglein and desmocolin (cadherins): linked to intracellualr intermediate filaments allow forces to be communicated over multiple cells

32

Hemidesmosomes

between cell and ECM
Transmembrane protein such as integrins

33

Belt desmosome

Transmembrane adhesion molcule: E.cadherins associated with intracellular actin: incluence cell shape and motility

34

Gap junctions

Communicating junctions: passage of signals and chemicals between cells

35

Gap junction examples

Connexon (hexamer of connexins): allow passage of ions, nucleotides, sugars, amino acids, vitamins, other small molcules

permeability decreaes with increase calcium or decreased pH

36

Classes of enzymes in lysozymes (6)

proteases
nucleases
lipases
glycosidases
phosphatases
sulfatases
all are acid hydrolases: ph of 5 works bests!

37

Mitochondria initiate protein synthesis with_____________.

N-formylmethionine

38

The warburg effect

upregulate glucose and glutamine cell uptake and decreased ATP per glucose molcule.
Growing cells and cancer cells that need to produce lipids nucleic acids and proteins instead of ATP

39

G protein coupled receptor pathway

7 membrane transmembrane protein --> ligand binds--> G protein with GDP exhcanged for GTP--> generates signal--> cAMP and inositol 1,4,5 triphosphate--> releases calcium from ER

40

Wnt Ligand pathway

Wnt binds to transmembrane frizzled family receptors--> recruits protein Disheveled--> disrups degeneration targeting complex--> beta catenin stabilizes--> translocates to nucleus--> forms transcriptional complex

41

Beta catenin

constantly targeted for ubiquitin directed proteosome degredation

42

Growth transcription factors (2)

MYC
JUN

43

Growth arrest transcription factor (1)

p53

44

How do transcription factors work?!

Interact directly or indirectly to recruit histone modifying enzymes, chromatin remodeling comlexes, and RNA polymerase

45

Second messenger examples (7)

Calcium
cAMP
cGMP
inositol triphosphate
Diacylglycerol
arachodonic acid
nitric oxide

46

Growth factors main functions

1. promote entry of cell into cell cycle.
2. relieve blocks on cell cycle progression (promoting replication).
3. prevent apoptosis
4. Enhance biosynthesis of cell components for daughter cells

47

Protooncogenes

gain of function mutations: cell prolifferation

48

EGF family growth factors

1. Epidermal growth factor
2. Transforming growth factor alpha
Both produced by macropahges and epithelial cells

49

EGF family growth factor receptors

4 membrane receptors with intrinsict tyrosine kinase activity
1. EGFR1
2.EGFR2

50

Platelet derived growth factor function

Induces fibroblasts, endothelial and smooth muscle prolfieration and matrix synthesis

51

VEGF funnction

1. endothelial migration, proliferation, formation of vascular lumen

Major angiogenic factor: induces blood vessels development in injury and tumor development

52

VEGF induced by

hypoxia induces hypoxia inducible factor (HIF-1) and then induce VEGF

PDGF and TGFalpha also induce VEGF

53

VEGF receptors

VEGF1,2,3: tyrosine kinases

VEGFR2: highly expressed in endothelium and most imoprtant angiogenesis

54

FGF functions

wound healing
hematopoeisis
cell development

55

TGF beta family proteins (4)

bone morphogenic proteins
activins
inhibins
mullerian inhibiting substances

56

TGF beta receptors

1.serine/threonine kinase receptor
2. induces phosphorylation of cytoplasmic transcription factor called Smads

57

TGF beta effects

1.drive scat formation
2. decreases inflammation
3. stimulates collagen fibronectin and proteoglycan productions
4. inhibits collagen degradation: decrease MMP and increase TIMP
5.Anti-inflammatory cytokine (inhibits lymphocyte proliferation, and activity of other leukocytes

58

basement membrane composition

Collagen 4 and laminin: major constituents

59

Fibrillar collagens (4)

type 1,2,3,5
linear fibrils stabilized with interchains of hydrogen bonds with lateral cross linking of triple helices by lysyl oxidase (vit C dependent)

60

Fibrillar collagen function

1.major component of bone cartilage tendon blood vessels and skin
2. wound healing and scars

61

Fibrillar collagen defects examples (2)

1. osteogenesis imperfecta
2. Ehlers danlos syndrome

62

Nonfibrillar collagen (3)

type 4,7,9
provides andhoring to basement membrane

63

Nonfibrillar collagen function

regulates collagen fibril diameter and regulate FACITs (fibril associated collagen with interrupted triple helices)
2. provides anchoring to basement membrane (type VII collagen)

64

FACITs

Fibril associated collagen with interrupting triple helices: example Type IX collagen in cartilage)

65

Adhesive glycoproteins (3)

1. fibronectin
2. laminin
3. integrins

66

Fibronectin

1. major component of ECM
2. woudng healing: scaffold for ECM, angiogenesis, epithelialization
3. binds to collagen, fibrin, heparin, proteoglycans, integrins

67

Integrins

alpha and beta subunits allow attachment to ECM (laminin and fibronectin) linking intracellular cytoskeleton to outside world

68

G1 phase cell cycle

presynthetic growth

69

G1 promoters and inhibitors

Promoter: Cyclin D and CDK4
Inhibitors: P16/15/18/19

70

S phase cell cycle

DNA synthesis

71

S phase promoter and inhibitors

promoters: Cyclin D and CDK6; Cyclin A CDK2; Cyclin A CDK1

Inhibitors: CDK inhibitors p21/27/57 (inhibitrs all cyclins nad CDK in S phase)

72

G2 phase cell cycle

premitotic growth

73

G2 phase promoters and inhibitors

Promoter: Cyclin B, CDK1

Inhibitors: CDK inhibitors p57/27/21

74

Most important checkpoint for DNA integrity before irreversible replication

G1-S phase

75

Check point that ensures accurate genetic replication

G2-S phase

76

Cyclin dependent kinase functions

Phosphorylate protein substrates by forming complexes with relevant cyclins