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Basic Principles Of Medicine 1-FTM 1 > Cells 1 > Flashcards

Cells 1 Flashcards

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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
What is the ER lumen like?
- single, continuous noise internal space | - separated from cytoplasm by the ER membrane
26
What is the clinical correlation of the rough endoplasmic reticulum ?
ER stress & unfolded protein sequence
27
What is the rough endoplasmic reticulum?
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
What are sER?
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
What are the Golgi faces?
Cis face - entry - cis Golgi network (CGN) Trans face - exit - trans Golgi network(TGN)
30
What are the functions of Golgi apparatus?
especially well developed in secretory cells - plasma cells - secrete antibodies - pancreatic acinar cells - secrete digestive enzymes
31
What is the Golgi apparatus?
Complex flattened, membrane cisternae Usually located next to the nucleus and centrosome -location is microtubule dependent
32
How do rER and Golgi apparatus, transport between each other?
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
What are the functions of the Golgi apparatus ?
1. Post-translational modification - glycosylation - sulfation - phosphorylation - proteolysis 2. Sorting 3. Packaging
34
What are the pathways of vesicular trafficking ?
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
What are lysosomes?
Digestive organelles- function: controlled intracellular digestion of macromolecules
36
Describe the structure of the lysosome
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
Describe Tay Sachs
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
What are the implications and results of dysfunctional lysosomes?
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
Patients with dysfunctional lysosomes can present with …
Normal birth, slower growth Bone and joint deformities Frequent lung infections and heart disease Other symptoms
40
Summarize the cause and effects of Hurler syndrome (MPS-1)
Faulty enzyme: a-L-iduronidas Accumulating product: dermatan sulphate Main organs affected: skeleton and nervous system
41
Summarize the cause and effects of pompe
Faulty enzyme: a- 1,4- glucosidase Accumulating product: glycogen Main organs affected: skeleton and nervous system
42
Summarize the cause and effects of Tay Sachs
Faulty enzymes: B-hexosaminidase Accumulating product: GM2 ganglioside System affected: nervous system
43
Summarize the cause and effects of Gaucher
Faulty enzyme: glucocerebrosidase Accumulating product: glucosylceramide Main organs affected: liver and spleen
44
Summarize the cause and effects of I-cell disease
Faulty enzyme: Phosphotransferase for M6P formation Accumulating product : lysosomal hydrolyzes are absent in lysosomes Main organs affected : skeleton and nervous system
45
What are the pathways to lysosomal digestion?
1. Phagocytosis 2. Endocytosis 3. Autophagy
46
Explain what is autophagy
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
What is the clinical correlation of autophagy?
Essential role. In starvation, cellular differentiation, cell death and cell aging
48
What is a proteosome?
Proteosome-mediated protein degradation - large protein complex - ATP dependent - degrade proteins without lysosomes Clinical correlation: proteosome inhibitors in cancer therapy
49
What is polyubiquitination?
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
Describe the structure of the mitochondria
2 membranes -outer and inner 2 compartments - inter membrane space - matrix
51
What is the primary function of the mitochondria?
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
What has the mitochondria evolved from?
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
Describe the structure-function of the outer membrane if the mitochondria
Contains porins - large channel forming porins - allows passage 9f small molecules (<5000 daltons) Contains several enzymes - phospholipase. - Acetyl coenzyme A synthase
54
Describe the structure function of the inter membrane space 9f the mitovhob
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
Describe the structure function of the inner membrane of the mitochondria
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
Describe the structure e abd function of the mitochondria matrix
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
How many mitichondrial disorders are there? What are often the results?
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
What is the main cause of myoclonic epilepsy with ragged red fibers (MERRF)?
About 80% of cases due to mutation in the MT-TK tRNA gene
59
What is the cause if lever hereditary optic neuropathy ?
- mutations in the MT-ND1, MT-ND4, MT-ND4L, or MT-ND6 genes | - degeneration of retina Ganglion cells
60
What are the functions of peroxisomes?
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
Where are peroxisomal proteins synthes8zed?
By free/cytoplasmic ribosomes Proteins must have a peroxisomal targeting signal
62
What are the clinical correlations of peroxisomes?
Dysfunctional peroxisomes Zellweger syndrome - cause - mutations in genes required for peroxisome function - defective import of peroxisomal proteins
63
What have peroxis9mes been specialized to do?
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

Basic Principles Of Medicine 1-FTM 1 (39 decks)

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