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Exam 3 Flashcards

1
Q

What is extracellular matrix?

A

-structure: 3D framework of fibers of proteins and glycoproteins
-function: maintains a useful 3D arrangement of tissues in body

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2
Q

What is ground substance?

A

aqueous gel of glycoproteins and proteoglycans that occupies the space between cellular and fibrillar elements of connective tissue.

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3
Q

What are proteoglycans?

A

a core protein and its covalently attached GAGs

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4
Q

What is a GAG?

A

a linear sequence of monosaccharides that is covalently attached to core protein

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5
Q

What is Hyaluronate?

A

polysaccharide to which proteins bind non-covalently

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6
Q

What are 3 different GAG names?

A

Keratan sulfate, chondroitin sulfate, and hyaluronate

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7
Q

What is the source of molecules of the ECM and ground substance?

A

cells

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8
Q

What is the level of organization in a human?

A

cells -> tissue -> organ -> organ system -> organism

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9
Q

What are tissues?

A

different types of cells comprise a tissue

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10
Q

What is an organ?

A

different types of tissues comprise an organ

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11
Q

What is an organ system?

A

different types of organs comprise an organ system

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12
Q

What is an organism?

A

different types of organ systems comprise an organism

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13
Q

What are the 4 types of tissues?

A

-nervous tissue
-epithelial tissue
-muscle tissue
-connective tissue

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14
Q

What is the general structure of connective tissue?

A

-ECM
-ground substance
-cells that hold onto the framework that include fibroblasts

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15
Q

What are some functions of fibroblasts?

A

-secretion of molecules for ECM
-secretion of cytokines

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16
Q

What are cytokines?

A

signaling molecules that coordinate the activity of immune cells, to include movement, differentiation, and division

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17
Q

What type of tissue is blood?

A

connective tissue

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18
Q

What is hematocrit?

A

percentage of blood that is occupied by erythrocytes (RBCs)

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19
Q

What is differentiation?

A

a change in the gene transcription pattern of a cell that ultimately resulting changes in appearance, capacities, behavior, etc..
-with very rare exceptions, every human cell have every human gene, they’re just not always expressed.

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20
Q

How do genes contribute to erythropoiesus?

A

-erythrocytes from stem cells
-stem cell divides -> 1 daughter cell (stem cell) 1daughter cell (differentiated)
-HSCP -> HSC -> CPC -> MPC -> erythrocytes

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21
Q

What is biological source of erythrocytes?

A

-lots of cell division, but daughter cells keep differentiating until erythrocytes -> then no more division just differentiation
-terminally differentiated cell at orthochromatic erythroblastc

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22
Q

Can we breathe easily everywhere?

A

no!

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23
Q

What is hypoxia?

A

-condition in which cells do not receive sufficient oxygen to function normally, or to survive

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24
Q

What is the minimum partial pressure of oxygen for normal human function?

A

14.5kP (109 mmHg) around 2,500m

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25
What are 4 major cells, tissues, and organs that contribute to our response to hypoxia?
-lungs -erythrocytes -kidneys -bones
26
What role do lungs play in body's response to hypoxia?
oxygen diffuses from atmosphere to bloodstream
27
What role do erythrocytes play in body's response to hypoxia?
majority of oxygen cargo is carried by intracellular hemoglobin
28
What role do kidneys play in body's response to hypoxia?
fibroblasts detect oxygen concentration
29
What role do bones play in body's response to hypoxia?
erythrocytes proliferate, generating more erythrocytes
30
Where does process of erythrocyte production start and end?
-the process begins in the kidney fibroblasts -the process ends in the bone marrow erythroblasts
31
How do our bodies generate erythrocytes?
-kidney synthesize and secrete erythropoietin (EPO) - EPO gets dumped into bloodstream -then blood goes to stem cells in bone marrow
32
What should you know about the structure of the kidney?
-outer layers of kidney = cortex -nephron = filters stuff out of blood
33
Is oxygen uniform throughout the kidney?
no
34
What are agents of oxygen detection?
kidney fibroblasts -fibroblasts in normoxic conditions are around medulla -fibroblasts move to higher oxygen concentration and make more EPO at hypoxia
35
What molecule in a kidney fibroblast is the oxygen sensor?
PHD2 -needs Fe + --H313 --D315 --H374 -when folded, they're close together and become oxygen sensor
36
What is hypoxia-inducible factor 1 alpha? (HIF-1alpha)
a transcription factor -red segment: necessary for binding to DNA -blue segment: necessary for binding to HIF-1 beta -3 targets for covalent modification: --Pro 402 --Pro 563 --Asn 804
37
How do PHD2 and HIF-1a interact?
PHD2 carry Fe ion and ascorbate (vit C) -> interacts w/ HIF-1a carrying O2 -> PHD2 hyroxylates HIF-1a -> HIF-1a now haws Pro that is hydroxylated -- in presence of sufficient concentration (normoxic conditions) of O2, this is always happening in kidney fibroblasts
38
What is HIF-1beta?
forms a heterodimer with HIF-1a to create HIF-1 -bond noncovalently -red segment: necessary for binding to DNA -blue segment: necessary for binding to HIF-1a
39
What happens when a protein is ubiquinated?
a ubiquinated protein is targeted for recycling by proteosomes -3 enzymes: E1, E2, E3
40
What is ubiquitin?
a small protein that can be covalently attached by an enzyme to a target protein
41
What is a proteasome?
multiprotein complex that digests proteins into amino acids and oligopeptides -tube made of multiple proteins -proteins that enter tube are about to be recycled -goes in protein -> comes out amino acid
42
How is HIF-1a activity regulated? (normoxic conditions)
in normoxic conditions, oxygen is present and PHD2 can use Fe to just grab O2 and hydroxylate Pros -> have hydroxyl group now so can bind to VHL -> can recruit E1, E2, & E3 -> HIF-1a destroyed
43
How is HIF-1a activity regulated? (hypoxic conditions)
in hypoxic conditions, there's not enough oxygen around -> if PDH2 doesn't get enough oxygen -> not all HIF-1a gets hydroxylated -> concentration of HIF-1a increases -> HIF-1a binds to HIF-1B -> form HIF-1 and acts as TF -> bind to specific seq of DNA that bind to promoters of certain genes -> upregulate/downregulate certain genes
44
What does binding to VHL lead to?
when concentration of O2 is low -> genes of EPO are transcribed and translated -> which is involved in stimulating erythroblasts to make more erythrocytes (RBCs)
45
What does HIF-1a do when active?
in hypoxic conditions -> create HIF-1 and bind to HRE -> other end can bind to P300
46
What is P300?
Histone Acetyl transferase (HAT) -transcriptional co-activator -acetylates histones ->brings no charge so DNA is more accessible
47
What is the core nucleotide sequence of HRE?
5'-RCGTG-3'
48
What is EPO?
structure: glycoprotein function: cytokine -detect decrease of oxygen
49
What is EPOR?
homodimer ~erythrocytes in bone marrow receive signal~ -EPOR needs to bind noncovalently to JAK 2 so receptor will be phosphorylated at tyrosine
50
What is structure of JAK 2?
kinase (take P from ATP and phosphorylates) -FERN binds noncovalently to EPOR
51
What is the structure of STAT5?
there are 7 different types of STAT proteins -dimers of STAT proteins are TFs
52
How does EPOR respond to EPO binding?
FERN is bound to EPOR receptor -> signal comes from EPO -> EPO changes shape (shifted) and kinase is activated
53
What happens after EPO binding at EPOR?
EPO binds -> causes 2 receptors to bind to each other -> JAK 2 activates and phosphorylates other JAK 2 -> og JAK 2 gets phosphorylated -> JAK 2 will phosphorylate tyrosine in own receptor -> now docking sites for STAT 5 -> STAT 5 binds and gets phosphorylated by JAK 2 -> STAT 5 lets go -> new STAT 5 comes along -> repeats until SHP1 comes along and binds to phosphorylated JAK 2 and starts dephosphorylating receptor
54
What is one target gene of STAT 5?
BCL-XL anti apoptotic protein
55
What is apoptosis?
cell suicide = orderly form of self destruction cell shrinks -> molecules digest themselves -> membrane doesn't break -> form blebs -> break off into little vesicles and hands to neighbors for them to phagocytize blebs
56
How is apoptosis regulated?
collection of proteins, either pro or anti apoptosis and depending on signals received, cell would respond either way
57
What should you know about BCL-XL?
BCL-XL is anti apoptotic so it is pro life -2 pro apoptosis proteins: BAK and BAX
58
How does BCL-XL interact with BAX?
BAX and BCL-XL bump into each other and bind -> leave membrane and go to cytoplasm -> leave and break apart -this cycle only continues if equal numbers of BAK and BCL-XL -if not enough BCL-XL then BAX keeps building on itself and build pore in membrane
59
If BCL-XL is insufficient to keep BAX in cytoplasm, and if pro-apoptotic signals arrive, then what does BAX do?
pore or opening extends through both membranes -> goes through mitochondrial membrane ~ kinda like attacking energy plants in war ~
60
What happens when BAX and/or BAK are allowed to dimerize?
Cyt C is gonna leave intermembrane space
61
Why is Cyt C important?
it is key participant in life-supporting function of ATP synthesis -cyt c is released from mitochondria -> binds to apaf-1 -> oligomerization -> forms pro-caspase 9 -> apoptosome -> interacts with pro-caspase 3 -> apoptosis
62
How is hypoxia tie in with BCL-XL?
hypoxia results in an increase of expression of BCL-XL in erythroblasts
63
How is cell cycle regulated?
cyclins -CDKs (cyclin dependent kinases)
64
What is cyclin E?
2 important functions: -interacts with CDK2 protein kinase to form serine/threonine-kinase holoenzyme complex -the cyclin subunit imparts substrate specificity to the complex
65
What is CDK2?
1 function: serine-threonine protein kinase
66
How do cyclin E and CDK2 interact?
they comprise a holoenzyme
67
What are the results of the cyclin E and CDK2 holoenzyme?
-can inhibit cell cycle inhibitors -activating cell-cycle activators -RB1: retinoblastoma-associated protein
68
What are E2F proteins?
transcription factors
69
Where does DNA replication begin?
ori site: specific seq of nucleotides
70
Are there ori sequences in EUK?
yes for some, no for others
71
What do researchers think contribute to functional replication origins?
-TFs -sequence motifs in DNA -histone modifications
72
What happens at an ori site?
2 strands at ori site are separated by other agents -RNA primer (5-10nt) allows new strands to be built off of template ~lagging strands can be 1,000-2,000nt in prokaryotes and 100-200nt in euk~
73
What are the 2 steps that initiate DNA replication?
-origin licensing -origin firing
74
What happens at origin licensing?
ORC -> CDC6 -> Cdt1
75
What happens at origin firing?
MCM2-7 double hexamer one ->DDK ->CDK the other: CDC45 -> GINS etc..
76
What is the ORC?
multi-protein complex made out of 6 proteins arranged roughly symmetrically, arranged in a ring to circle the ori -ORC 1, ORC 2, ORC 3, ORC 4, ORC 5, CDC 6
77
Can ORC proteins interact with chromatin?
yep! -bind and create a chain of binding from nucleosome histones to ORC proteins
78
What is the MCM complex?
the catalytic core of a larger helicase complex that unwinds parental DNA -made of ring shaped structure with 6 proteins: MCM2-MCM7
79
How is a pre-replicative complex (pre-RC) assembled?
ORC1-5 ORC 6 CDC 6 CDT1 MCM2-7 ORC1-6 and CDC6 bind -> then bind to DNA -> CDT1 causes MCM2-7 to open and slip around double stranded DNA -> then closes up again
80
When is a pre-RC assembled?
in the G1 phase -assembly of a pre-RC requires cyclin E
81
What is the GINS complex?
-structure: a complex of four proteins -function: that mediates the assembly of replication factors around the MCM helicase during DNA replication
82
What is a CMG helicase complex?
-structure: CDC45, MCM2-7, and GINS -function: separation of DNA strands
83
How are CMG complexes assembled?
84
How is the dsDNA duplex melted?
both MCM complexes contribute to the separation of DNA strands

Biol 300 (6 decks)

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