Cells 1 Flashcards

1
Q

What are the 3 domains of life?

A
  1. Bacteria - prokaryotic cells
  2. Archaea-prokaryotic cells
  3. Eukaryota- eukaryotic cells
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2
Q

What is the largest organelle in a eukaryotic cell?

A

Cell nucleus

About 10% in cell volume

DNA is sequestered in the nucleus

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3
Q

List the components of the nucleus

A

Nuclear envelope

Nuclear lamina

Nuclear pores

Nucleolus

Nucleoplasm

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4
Q

Contrast the inner nuclear membrane and outer nuclear membrane

A

Inner nuclear membrane

  • faces the nucleoplasm
  • in contact with the nuclear lamina
    • functions as a scaffold stabilizing the nuclear envelope

Outer nuclear membrane

  • faces the cytoplasm
  • continuous with endoplasmic reticulum (ER)
  • cytoplasmic surface contains ribosomes
    • rough ER
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5
Q

What is the nuclear lamina?

A

This, sheet mesh work beneath the inner nuclear membrane

  • nuclear lamins
    - type of intermediate filaments
    - lamin A & B
    - Clinical correlation: Lamin A mutation in Hutchinso-Gifford Progeria & syndrome & other laminopathies
  • Scaffold for nuclear envelope, chromatin & nuclear pores
    - disassembles during mitosis
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6
Q

How large is the nuclear pore complex?

A

Span the inner and outer nuclear membranes

- 80-100 Na in diameter

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7
Q

What is the nuclear pore complex made up of?

A

Made up of more than 50 proteins

-nucleoporins

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8
Q

How much Nuclear pore complexes are in a nuclear envelope?

A

3000-4000

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9
Q

What is the function of the nuclear pore complex?

A

Allows transport of molecules between the nucleus and cytoplasm

- ions and molecules < 9nm to diffuse freely through the pore
 - molecules 9> Nm must be transported by active transport
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10
Q

What is the function of nucleolus?

A

Site of ribosome production

  • ribosomal RNA is transcribed
  • ribosomal subunits assembled
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11
Q

What are the 3 zones of the nucleolus?

A

Fibrillar center (FC)

  • pale staining region
  • DNA loops of 5 chromosomes
    • 13, 14, 15,21, & 22
    • contain rRNA genes
Fibrillar material (F)
    -transcription of rRNA genes
Granular material (G)
     -initial ribosomal assembly
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12
Q

Summarize chromatin structure

A

Chromosomes in various degrees of uncoiling

  • packaged into Nucleosomes
    • Complex of DNA and proteins called histones
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13
Q

What are the types of chromatin?

A

Euchromatin- lightly staining, less condensed chromatin, more transcriptionally active

Heterochromatin- densely staining, highly condensed chromatin, less transcriptionally active

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14
Q

What is a nucleosome?

A

Fundamental structural unit of chromatin

Macro molecular complex
-8 histone molecule (octamer)

  • 2 loops of DNA wrap around the core octamer
  • “beads on a string “

Found in both euchromatin and heterochromatin

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15
Q

What is a telomere?

A

At the ends of a chromosome

  • Repeated sequences that allow the ends of the chromosome to be allowed
  • Clinical correlation: telomerase enzyme , cancer & aging
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16
Q

What is the replication origin?

A

Location where DNA replication begins

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17
Q

What is a centromere?

A
  • centric heterochromatin
  • persists throughout interphase
  • constricted region that holds sister chromatids together
  • also the site of kinetochore formation
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18
Q

Each chromosome contains specialized nucleotide sequences…

A

Bind specific proteins for replication and segregation

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19
Q

How are ribosomes produced?

A

In the nucleus, leave the nucleus and enter cytoplasm

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20
Q

What are the 2 populations 9f ribosomes?

A

Membrane-bind ribosomes

Free ribosomes

Polyribosome
-many ribosome bound to a single mRNA molecule

Clinical corrlelstion: ribosomopathies

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21
Q

What is the function of membrane-bound ribosome?

A

Attached to cytoplasmic surface of the ER membrane
-Rough ER

mRNA contains an ER signal sequence

Synthesize proteins that are being translocated into the ER lumen

- lysosomal proteins
- secreted proteins
- plasma membrane proteins
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22
Q

What are the functions are free ribosomes?

A

Unattached to any membrane
-mRNA does NOT have ER signal sequence

Synthesize all other proteins

  • nuclear proteins
  • mitochondrial proteins
  • cytosolic proteins
  • peroxisomal proteins
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23
Q

What are the two regions of the ER?

A
  1. Smooth ER- functions in synthesis of lipids & detoxification
  2. Rough ER- functions in synthesis of proteins destined for plasma membrane, lysosomes or secretion
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24
Q

What is an endoplasmic reticulum?

A

Interconnected network of branching tubules & flattened sacs distributed throughout the cytoplasm

  • At certain sites, the ER membrane is continuous with the outer nuclear envelope membrane
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25
Q

What is the ER lumen like?

A
  • single, continuous noise internal space

- separated from cytoplasm by the ER membrane

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26
Q

What is the clinical correlation of the rough endoplasmic reticulum ?

A

ER stress & unfolded protein sequence

27
Q

What is the rough endoplasmic reticulum?

A

Region with ribosomes attached to cytoplasmic surface of the ER

-Only mRNA molecules with an ER signal sequence bind to rER membranes

  • Abundant in cells specialized in protein synthesis
    • Ex. Secretory cells producing proteins for extracellular export

-Site of initial post-translational modifications & folding

28
Q

What are sER?

A

Region of the ER that lacks bound ribosomes

Abundant in cells specialized in lipid metabolism
-well developed in cells that synthesize and secrete steroids

  • Plays a major role in detoxification
    • Ex. Hepatocytes & detoxifying enzymes
      • cytochrome P450 systems

Also functions to sequester calcium
-Ex. Muscle cells & sarcoplasmic reticulum

29
Q

What are the Golgi faces?

A

Cis face

  • entry
  • cis Golgi network (CGN)

Trans face

  • exit
  • trans Golgi network(TGN)
30
Q

What are the functions of Golgi apparatus?

A

especially well developed in secretory cells

  • plasma cells
    • secrete antibodies
  • pancreatic acinar cells
    • secrete digestive enzymes
31
Q

What is the Golgi apparatus?

A

Complex flattened, membrane cisternae

Usually located next to the nucleus and centrosome
-location is microtubule dependent

32
Q

How do rER and Golgi apparatus, transport between each other?

A

CoA tamer-coated vesicles
-mediate bidirectional traffic vesicles between the ER and Golgi apparatus

COP-1 costed vesicles

  • retrograde transport (cis-Golgi to rER)
  • CGN back to rER

COP-II coated vesicles

  • Anterograde transport(rER to cis-Golgi)
  • Carry newly synthesized proteins from rER to CGN
33
Q

What are the functions of the Golgi apparatus ?

A
  1. Post-translational modification
    - glycosylation
    - sulfation
    - phosphorylation
    - proteolysis
  2. Sorting
  3. Packaging
34
Q

What are the pathways of vesicular trafficking ?

A
  1. Constitutive secretory pathway
    - basolateral
    - apical
    - vesicles produced for continuous secretion
    e. g. fibroblasts secreting ECM components
  2. Regulated secretory pathway
    • vesicles are stored & secreted with stimulus
      • e.g. neurons, B cells (endocrine) & acinar cells (exocrine) of pancreas
  3. Lysosomal pathway
35
Q

What are lysosomes?

A

Digestive organelles- function: controlled intracellular digestion of macromolecules

36
Q

Describe the structure of the lysosome

A

Membrane-enclosed compartments filled with about 40 types of hydro lytic enzymes

- acid hydroolases
- require an acidic environment 
    - low pH (about 4.7)

Clinical correlation: lysosomal storage diseases

37
Q

Describe Tay Sachs

A

First LSD characterized
-warren Tay (1881) and Bernard Sachs(1896)

Deficiency of HEXA - B-Hexosaminidase A, a-subunit

Autosomal recessive disorder - chromosome 15q24.1

Results in the accumulation of GM2 ganglioside

Death of neurons in the brain and spinal cord

38
Q

What are the implications and results of dysfunctional lysosomes?

A

Dysfunctional lysosomes

> 40 LSDs

-often result from mutations in genes that encode lysosomal enzymes

Results

  • accumulation of undigested products
  • disruption of normal cell function
  • cell death
39
Q

Patients with dysfunctional lysosomes can present with …

A

Normal birth, slower growth

Bone and joint deformities

Frequent lung infections and heart disease

Other symptoms

40
Q

Summarize the cause and effects of Hurler syndrome (MPS-1)

A

Faulty enzyme: a-L-iduronidas
Accumulating product: dermatan sulphate

Main organs affected: skeleton and nervous system

41
Q

Summarize the cause and effects of pompe

A

Faulty enzyme: a- 1,4- glucosidase

Accumulating product: glycogen

Main organs affected: skeleton and nervous system

42
Q

Summarize the cause and effects of Tay Sachs

A

Faulty enzymes: B-hexosaminidase

Accumulating product: GM2 ganglioside

System affected: nervous system

43
Q

Summarize the cause and effects of Gaucher

A

Faulty enzyme: glucocerebrosidase

Accumulating product: glucosylceramide

Main organs affected: liver and spleen

44
Q

Summarize the cause and effects of I-cell disease

A

Faulty enzyme: Phosphotransferase for M6P formation

Accumulating product : lysosomal hydrolyzes are absent in lysosomes

Main organs affected : skeleton and nervous system

45
Q

What are the pathways to lysosomal digestion?

A
  1. Phagocytosis
  2. Endocytosis
  3. Autophagy
46
Q

Explain what is autophagy

A

Major cellular pathway to degrade proteins & organelles in the lysosome

“Self-eating”

  1. Intracellular membrane surrounds the organelle and cytoplasm
  2. Auto phagosome formed.
    • double membrane vacuole
  3. Fusion of auto phagosome with lysosome
  4. Contents are degraded, recycled and reused
47
Q

What is the clinical correlation of autophagy?

A

Essential role. In starvation, cellular differentiation, cell death and cell aging

48
Q

What is a proteosome?

A

Proteosome-mediated protein degradation

- large protein complex 
- ATP dependent 
- degrade proteins without lysosomes

Clinical correlation: proteosome inhibitors in cancer therapy

49
Q

What is polyubiquitination?

A

Proteins targeted for destruction are covalently tagged with the ubiquitin protein

Destruction of abnormal proteins & normal short lived regulatory proteins
-Ex. Cyclins, transcription factors, tumor suppressors

50
Q

Describe the structure of the mitochondria

A

2 membranes
-outer and inner

2 compartments

  • inter membrane space
  • matrix
51
Q

What is the primary function of the mitochondria?

A

Generate ATP

  • citric acid cycle
  • oxidative phosphorylation
  • B-oxidation of fatty acids
  • Abundant in cells that generate and expend large amounts of energy
    • striated muscle cells

Clinical correlation: mitochondriopathies

52
Q

What has the mitochondria evolved from?

A

From aerobic bacteria that were engulfed by primitive eukaryotic cells

  • double stranded circular DNA
    • maternally derived
    • mitochondrial genes
      • 13 proteins (electron transport chain)
        • NADH dehydrogenase(7), ATP synthase(2), cytochrome c oxidase (3), cytochrome b
      • 22 tRNAs
      • 2 rRNAs
53
Q

Describe the structure-function of the outer membrane if the mitochondria

A

Contains porins

  • large channel forming porins
    • allows passage 9f small molecules (<5000 daltons)

Contains several enzymes

- phospholipase. 
- Acetyl coenzyme A synthase
54
Q

Describe the structure function of the inter membrane space 9f the mitovhob

A

Space between the inner and outer membranes

  • contains specific enzymes that use ATP generated by the inner membrane
    • creatine kinase
    • adenylwte kinase

Cytochrome c
-important factor in intrinsic apoptosis pathway

55
Q

Describe the structure function of the inner membrane of the mitochondria

A

Thinner and thrown into folds
-cristae

3 major functions:

  1. Oxidation reactions:
    - respiratory electron transport chain
  2. Synthesize ATP
    - ATP synthase
  3. Regulate metabolite transport into and out of the matrix
56
Q

Describe the structure e abd function of the mitochondria matrix

A

Mixture of hundreds of enzymes

  • oxidation of Pyruvate & fatty acids
  • citric acid cycle

Matrix granules
-storage sites for Ca2+ & other divalent cations

-mitichondria DNA, ribosomes and tRNAs

57
Q

How many mitichondrial disorders are there? What are often the results?

A

Over 40 different disorders

-mutations in mitochondrial genes

  • results in defects in mitochondrial enzymes required for ATP production
    • dysfunctional mitichondrial respiratory chain

Typically affects tissues that require large amounts of ATP

Like neurons or muscles

58
Q

What is the main cause of myoclonic epilepsy with ragged red fibers (MERRF)?

A

About 80% of cases due to mutation in the MT-TK tRNA gene

59
Q

What is the cause if lever hereditary optic neuropathy ?

A
  • mutations in the MT-ND1, MT-ND4, MT-ND4L, or MT-ND6 genes

- degeneration of retina Ganglion cells

60
Q

What are the functions of peroxisomes?

A

Important role in fat metabolism

- very long chain fatty acid (VLFCA) beta-oxidation 
- catalyze initial reactions in formation of plasmagens 
    - abundant class of phospholipids in myelin
    - deficiencies cause profound abnormalities in myelination of nerve cells
61
Q

Where are peroxisomal proteins synthes8zed?

A

By free/cytoplasmic ribosomes

Proteins must have a peroxisomal targeting signal

62
Q

What are the clinical correlations of peroxisomes?

A

Dysfunctional peroxisomes

Zellweger syndrome

- cause 
    - mutations in genes required for peroxisome function
    - defective import of peroxisomal proteins
63
Q

What have peroxis9mes been specialized to do?

A

Specialized to compartmentalize & degrade toxic reactive oxygen molecules

  • contain catalase & other peroxidase
    • converts hydrogen peroxide to oxygen and water
  • Particularly important in hepatocytes
    • detoxification of alcohols