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365 Cards in this Set

  • Front
  • Back
Platelets are cell fragments and can’t make new anything, let alone new COX;
But they can USE cox and other enzymes
Reversible inhibitors are no good at:
decreasing risk of CVD
Rb-EF2 complex =
transcriptional *repressor*

- deacetylates histones, keeping S-phase genes from being expressed
Retinoblastoma = eye tumor;

(3)
1. aggressive - needs early diagnosis

2. familial inheritance is most common form of contraction

3. ~ two-hit hypothesis
sproadic RB is NOT
familial;

rather, a rare inactivation of both alleles
tumor suppressor =
inhibitor of cell cycle progression = brakes

e.g. Rb
mutation in a tumor suppressor =>
*loss* of function
proto-oncogene =
stimulator of cell cycle progression = acceleration

e.g. Cyclin D
mutation in a proto-oncogene =>
oncogene => GAIN of function
Cyclin D overexpression =>
cancers
RB underexpression =>
cancers
Rule #3: a cell must not start to replicate DNA unless its mass is
sufficient to support the replication

~ G1
***what is cmyc?***
a TF for cell growth
cmyc sits on a promoter, => increase in
expression of protein synthesis genes
***what activates cmyc to inc.expression of protein synthesis genes?***
***P'n, via both sides of TKR***
overexpression of cmyc =>
leukemias, lymphomas
Rule #4: a cell must replicate DNA once and
only once during each division
***what Cyclin/Cdk combo drives replication?***
Cyclin E/ Cdk 2
Licensing:

(2)
1. G1

2. helicases load onto origins of replication
Firing:

(2)
1. S phase

2. helicases, DNA polym, etc. are activated => replication => two sets of chromosomes in G2
****what does Cyclin E/Cdk 2 do at the same time during replication?****

(2)
1. inhibits re-licensing

2. stimulates Firing
mutation => re-licensing (improper) =>=>
broken chromosomes => cell death from lots of erros

- or tumor from a little re-licensing
how do cyclins cycle?

(2)
1. regulated induction

2. regulated destruction
Ubiquitination: what do the E's do?
E1 activates Ub,

E2 carries it to E3,

E3 targets it to specific proteins

=> proteosome => degradation
Cullin (a type of E3) =
scaffold

Roc = necessary catalyst
what is responsible for Cyclin E degradation?
**Cullin 1**
by what process is Cyclin E/Cdk2 degraded?
***Cyclin E/Cdk2 Phosphorylates itself***

=> Cullin binds => Ub'n => targeted to proteosome
what activates Cdk's?

(2)
1. cyclin binding

2. P'n of Cdk activation loop
what inhibits Cdk's?

(3)
1. cyclin destruction

2. de-P'n of activation loop

3. ***Cdk inhibitor binding***
***2 examples of Cdk inhibitors:***
p16,

p27
which Cdk's do p16's inhibit?
***Cdk's 4 and 6 ONLY***
in many cancers, both alleles for p16 are
lost
***which Cdk's do p27's inhibit?***
Cdk's 1 and 2***
***p16's and p27's are highly expressed in:

(3)
quiescent, senescent, and terminally-differentiated cells
mice lacking p27 are:
larger

- Cyclin E/Cdk2's are *unchecked* => cancer in some tissues
mice lacking Skp2 are:
smaller

(Skp = an E2 Ub. that carries p27)

- p27 isn't degraded, continues to repress Cyclin E/Cdk2 => can't initiate S-phase as much
***cancer cells typically affect only:***
one point of a pathway

- but they affect *two pathways* => cancer
lipoprotein =
transport for Tg's pl's, free cholesterol, and CE
center of lipoproteins =

(2)
CE and TG's
outside of lipoproteins =

(3)
free cholesterol, pl's, and apoproteins
lipoproteins are classified by:
density;

chylomicron < VLDL < LDL <HDL
density of lipoporteins:

(3)
1, inversely related to size

2. inversely related to TG content

3. directly proportional to protein and pl content
not dense =
very big
chylomicrons are the _____________, HDL's are the ___________
largest;

smallest
apoA ~

(2)
1. targets HDL to per. tissues

2. activation of LCAT
apoB-100 ~
***binding of LDL to LDL receptors***
apoC =
activator of LPL

(lipoprotein lipase)
apoE ~
binding of chylomicron/VLDL/HDL remnants to the liver
apoE + apoB-100 ~
binding of IDL to liver
Lipoprotein Lipase:

(3)
1. located in endo. cells *adjacent to* peripheral tissue, especially adipose

2. *required* for removal of TG's from chylo's and VLDL

3. insulin inc. its production AND translocation
Hepatic Lipase:

(3)
1. located near liver

2. hydrolyzes TG's from chylo's and VLDL in their conversion to LDL's



3. unregulated
what LPL doesn't remove,
hepatic lipase does
***removal of TG's =>
remnant particles
cholesterol can diffuse:

(2)
1. among lipoproteins

2. between lipoproteins and tissue
half-life of chylomicron =
minutes

- ***normally, there are NO chylomicrons in the the blood during fed state***
half-life of VLDL's =
days

- also a rapid process - shouldn't see VLDL in blood in fed state
reverse cholesterol transport ~
cholesterol from peripheral tissue to liver
3 critical enzymes for reverse cholesterol transport:
1. LCAT

2. CETP

3. PLTP
***what does LCAT do?***
makes free cholesterol into CE

- thereby trapping it in the lipoproteins
***what does CETP do?***
transfers CE from HDL to:

V / I / LDL
***what does PLTP do?***
transfers pl's and TG's from: VLDL, IDL, LDL

to: HDL
apoA - 3 jobs:
1. target HDL to per. tissue, via apo A receptors

2. activates ABC1

3. activates LCAT
what does the ABC1 transporter do?
increases efflux of cholesterol FROM per. tissue into HDL
HDL = repository of
apoproteins
Reverse Cholesterol Transport pathway:

(6)
1. HDL made by liver and intestine, has apo A and apo E

2. HDLs pick up apoC and apoE from chylomicron/VLDL remnants

3. bind apoA receptors on per. tissues, take up cholesterol
=> HDL3

4. LCAT (on HDL) traps chol. as CE

5. CETP (on HDL) transfers CE to V, I, and LDL => delivery of chol. to liver

6. PLTP (on HDL) transfers TG's and pl's to HDL3
=> HDL2
=> internalized by liver
purpose of exogenous pathway:
transport dietary lipids to peripheral tissue
purpose of edogenous pathway:
transport of lipids synthesized by the liver
purpose of reverse cholesterol pathway:
transport cholesterol from peripheral tissues to liver
collagen cross-links b/w and within helices =>
strength
fibraller collagen ~
bone, cartilage, tendon, skin, etc.
non-fibraller collagen ~
basement membrane
fibronectins:

(4)
1. increase adhesion of cells

2. link cells to other ECM components

3. form on the surface of a cell

4. may increase or dec. cell migration via pathways
***RGD =
fibronectin's cell-binding domain
**integrellin = structural agonist of
RGD;

=> blocks RGD => dec. binding capacity of platelets => disruption of blood clot formation
elastin is covered by:
**fibrillin**
mutations in fibrillin (on top of elastin) =>
Marfa's Syndrome

(rupture of aorta)
integrins =
***major cell receptors for MANY ECM proteins

- connect ECM to cell's cytoskeleton
only B4 integrins ~
IF's/hemidesmosomes

- the rest => actin filaments
**3 important integrins:
1. a5B1

2. B2

3. aIIbB3
a5B1 integrins only bind to
***RGD sequence of *fibronectin ***
B2 integrins are only found on
leukocytes

=> FIRM adhesion of leukocytes to endo cells
a II b B3 integrins are found ONLY on
platelets

- bind to *fibrin*
a II b B3 integrins are normally inactive, but become able to bind fibrin/fibrinogen when
platelets are activated
missing or mutated a II b B3 integrins =>
Glanzmann's

= don't form effective blood clots
***a II b B3 integrins are targeted by:***

(2)
1. integrellin

2. Reopro, an AB
why target a II b B3 integrins?
dec. blood clots
**focal adhesion =
site of connection b/w integrins and ECM proteins
FAK =
cytosolic tyrosine kinase
when integrins engage the ECM, FAK is activated =>
growth, differentiation, and migration of cells

- FAK is overexpressed in some cancers
Leukocyte Adhesion Deficiency =
leukocytes don't express B2 integrins
LAD =>
failure to adhere to endo cells => failure to mount inflammatory response/combat infections
normal leukocyte rolling ~
selectins
once B2 integrins are activated on leukocytes, leukocytes can bind to:
**ICAM-1** on cell surface


=> strong adhesion => leukocyte flattens => enters cells
***for T-lymphocytes, what is the integrin that allows them to bind, and what do they bind to:
a4B1,

VCAM

=> strong adhesion => effect in cells
Tysabri, an AB against a4B1 => blocking lymphocytes => treatment of
MS, Crohn's
complex carbs =
sugars + prot. or sugars + lipids
GAG's =
polymers of negative disaccharide repeats
proteoglycans =
GAG chains hanging off a protein

- mostly all carbohydrate
glycoprotein =
mostly protein
4 properties of proteoglycans/GAG's:
1. repulsion via negative charges

2. lubricant

3. shock absorber

4. structure
which components of the membrane and ECM undergo turnover?
**ALL of them
GAG's/proteoglycans are endocytosed, =>
lysosomes
defects in degradative enzymes => GAG accumulation in both:
lysosomes and ECM => debilitating deformities
the N-terminal AA sequence of glycoproteins targets them to
ER/Golgi
O-linked glycoprotein refers to:
the OH of Ser/Thr
N-linked glycoprotein refers to:

2 facts:
the NH2 of Asn


1. **MOST glycoproteins are N-linked**

2. N-linked = targeted to ECM or cell surface
which enzyme adds mannose-6-P to glycoproteins, for degradation?
phosphotransferase
if something other than mannose-6-P is attached to a glycoprotein, the glycoprotein is targeted to:
the cell surface or ECM
function of glycoproteins =
**zip codes**

=> to lysosomes, plasma, vesicles bound for ECM
most glycolipids are:
sphingolipids
sphingosine =
long-chain amino alcohol
there are lots of sphingolipids in the
nervous system

- neurons, myelin
sphingolipidosis =
genetic defect in sphingolipid metabolism

- not breaking down sphingolipids

- a kind of lysosomal disease
sphingolipidosis =>
MR, early death
sphingolipids are degraded in
lysosomes too
accumulation of sphingolipids =>
pathology - cells choke to death

- same is true for accumulation of GAG's, surface glycoproteins
4 Sphingomyelin diseases:
1. Krabbe

2. MLD

3. Tay-Sachs

4. Niemann Pick A+B


all ~ defects in degradation
which lipids accumulate in Krabbe disease?

(2)
1. cerebroside

2. psychosine
which lipid accumulates in MLD?

(metachromatic leukodystrophy)
sulfatide
which lipid accumulates in Tay-Sachs?
ganglioside
which lipid accumulates in Niemann Pick A+B?
sphingomyelin
sphingomyelin is found in:
ALL cells
where are gangliosides mostly found?
neurons
sulfatide =
sulfated cerebroside
disruption of regular turnover/catabolism =>
destruction of CNS myelin
AGE =>
neuropathy, athero, etc.
ceramide =
sphingosine + FA
cerebroside =
major myelin lipid
gangliosides ~

(2)
big sugar heads, sialic acid
***muccopolysaccharidosis =
defective catabolism of GAG's
2 examples of muccopolysaccharidosis:
1. Hunter's syndrome

2. Hurley's syndrome
effects of mineralcorticoids =

(3)
1. inc. blood pressure

2. inc. blood volume

3. inc. vasoconstriction
how do mineralcorticoids achieve their effects? via:

(2)
1. inc. retention of Na+ and H2O

2. inc. excretion of K+ and H+
effects of glucocorticoids =

(2)
1. inc. fuel

2. dec. immune response
androgens and estrogens increase
male and female sex characteristics, respectively
***ACE inhibitors =>
**dec. in BP**
**what inhibits aldosterone production?**
cGMP
how are lipids transported through the blood?
BOUND to vehicles
how many Zn2+ binding fingers do steroid hormones have?
2
the 1st finger of steroid hormones controls:
DNA binding
the 2nd finger of steroid hormones controls:
dimerization of hormone receptor
HRE = hormone response element =
**promoter** of hormone-responsive genes
HRE's are:
inverted or direct repeats of 2 "half sites"
a hormone receptor's specificity for binding to a particular gene depends on:

(2)
1. the orientation of the repeats

2. spacing between the repeats
***what kind of HRE's do homodimer receptors bind to?***
***inverted-repeat HRE's***
***what kind of HRE's do heterodimeric receptors bind to?***
**direct-repeat HRE's**
how does a free hormone enter the cell?
by diffusion
what binds HRE?
the hormone-receptor complex
what are the 2 classes of steroid hormones, in terms of binding location?
1. cytoplasmic class

2. nuclear class
cytoplasmic class hormones bind the receptor in:
the cytosplasm first

=> dissociate from heat-shock proteins
=> go to nucleus
which steroids belong in the cytoplasmic class?
MC's,

GC's
steroids in the nuclear class bind to their receptor only in:
the nucleus

- Androgens, Estrogens, Progesterone
steroid hormones only regulate:
transcription
3 known targets of cortisol:
1. pyruvate carboxylase => GNG

2. glucose-6-phosphatase => glucose release

3. transaminase
GC's inhibit expression of:

(2)
1. cytokine genes (~activation of immune cells)

2. adhesion genes (~draw immune cells to inflammation )
GC's inhibit immune response via
increased expression of inhibitors
congenital adrenal hyperplasia (CAH) =
disruption of adrenal steroid secretion via defect in enzymes
95% of CAH cases involve a defect in:
21a-hydroxylase
5% of CAH cases involve a defect in:
11B-hydroxylase
which enzymes, if lost, has the most devastating effects on steroid hormones?
3B-ol-DH
***defects in 21a or 11B-hydroxylase have NO effects on:***
gonadal steroids
***dec. in MC's and GC's =>
accumulation of intermediates => inc. in DHEA => male sex characteristics
DHEA =
Androgen
****which enzymes directly measures amount of corticosteroids?****
17-OHCS
****which enzyme directly measures amount of gonadal hormones?***
17-KS
G-actin =
free actin
G-actin has **ATPase activity**. hydrolysis occurs:
randomly*
F-actin =
filament-string actin
***where does attachment of G-actin onto F-actin occur?***
at the **barbed end**
old actin =
ADP-bound actin
young actin =
ATP-bound actin
some proteins bind preferentially to either
old or new actin
regulation of actin involves a number of proteins:

(4)
1. Arp 2/3

2. cofilin

3. phalloides

4. cytochalasin
***Arp2/3 complex =>
polymerization of actin via branching

(binds to sides and pointed ends)
cofilin on actin =>
depolymerization of actin
cofilin preferentially binds to:
ADP-actin
phalloides of mushrooms =>
depolym
phalloides binds along
length and on pointed ends of actin
cytochalasin =>
depolymerization
cytochalasin binds at the
barbed ends of actin filaments
filamin =
dimerized cross-linker of actin
filamin =>
networks and bundles
severing of actin network =>
reorganization
what does gelsolin do to actin?
**severs** actin filaments in response to increased ic Ca2+
cell extension occurs via
actin
thin filament =
actin
in muscle, actin is anchored at the
barbed ends, to the Z-line
Myosin II is found in:
ALL muscle,

as well as some non-muscle tissue
LMM =>

(1)
forming filaments
HMM =>

(2)
binding actin,

hydrolyzing ATP for contraction
stimulus => Ca2+ from SR => floods muscle =>
binds troponin complex => movement of tropomyosin => myosin heads bind actin
myosin II in non-muscle: P'n of light chain =>
loop formation
Rho-GTP function =
activates Arp2/3
Rho ~
Ras superfamily
Cdc42 => WASP =>
ARP2/3 => polymerization
defect in WASP => dec. WASP in:
leukocytes

=> leukocytes migrate poorly

=> infection
what does RhoA activate?
1. stress fibers

2. focal adhesions
what does Rac 1 activate?
lamellipodia
what does Cdc42 activate?
filopodia
3 phases of cell migration =
1. extension (via actin polym.)

2. adhesion (integrins)

3. contraction (myosin via Rho)
actin in non-muscle cells:

(2)
1. G-actin reservoir

2. F-actin in networks or bundles
F-actin bundles are either:
contractile (e.g. contractile ring)

or non-contractile (e.g.microvilli)
in contractile bundles, pointed ends point in
opposite directions
in tight parallel F-actin bundles, pointed ends all run:
in the same direction
the type of actin bundle made depends on the
cross-linking proteins

- more space = looser = e.g. myosin binds
filopodia =
exploratory organelles
WBC filopodia ~
first contact with bacteria
circumferential belt =
type of contractile bundle near apical surface of epithelial cells
stress fibers:

(4)
1. rare in most cells

2. responsible for scar contracture

3. function = close wounds

4, disassembled in cancer cells, mitosis
scar contracture =
tightening of the skin after a serious burn
4 kinds of cytoskeletal diseases:
1. spherocytosis

2. elliptocytosis

3. DMD

4. Usher's
spherocytosis =
mutation in ankyrin => abnormal cell shape => hemolysis
elliptocytosis =
mutation in spectrin => abnormal cell shape => hemolysis
DMD =
mutation in dystrophin => progressive death of skeletal muscle
Usher's syndrome =
defect in myosin 7 => blindness/deafness
locations of MT's:
1. cilia/flagella (movement of fluid/sperm)

2. cytoplasm (movement of organelles)

3. mitosis (movement of chromosomes)
each MT subunit consists of
13 monomer rows
dynein ~
MT movement
dynein + no crosslinks b/w MT's =>
MT sliding
dynein + crosslinks =>
MT bending
basal body =
9 + 2 arrangement, found in cilia/flagella
cilia = movement organs as well as:
sensory organs
primary cilium sticks out => fluid =>
bends cilium => signal sent
2 disease of cilia:
1. polycystic kidney disease

2. Kartagener's syndrome
Kartagener's syndrome =
paralyzed cilia and flagella

=> inc. respiratory infections, male sterility
MT doublet ~
cilia
MT triplet ~
centriole
where does addition and removal of MT subunits occur?
**at the positive end**

- the negative end is anchored to the centrosome
MT subunits are stable when they are:
GTP-bound
hydrolysis of GTP cap off of MT subunits =>
catastrophe
what does taxol do?
prevent MT depolymerization
cell checkpoints make sure that the previous phase has been:
completed correctly
checkpoint proteins are NOT
involved in the cycle phase, but monitor it
loss of checkpoint =>
genetic instability
P'n of Y15 of Cdk's =>
INactivation
which protein P's Y15 of Cdk's?
Wee1
which protein de-P's Cdk's?
**Cdc25**

=> activation of Cdk's
each cell must receive a complete:
set of replicated DNA
what holds sister chromatids together?
**cohesin**
how does the cell get rid of cohesin so that the chromatids can split?
**separase** (via APC activation)
if DNA is damaged, the cell must repair it before:
division
in absence of damage, p53 is kept at:
low levels
what keeps p53 at regular low levels?
Mdm2

- an **E3 ubiquinating** protein
DNA damage => P'n of p53 =>
Mdm2 dissociates => p53 free to activate p21

=> inhibition of Cdk's
***p53 is activated by:***
almost any cell stress or damage
high p53 (as with DNA damage) =>
arrest, repair, apoptosis, senescence
stress environment => increase in
ARF => inhibition of Mdm2 => increased p53 => inhibition of cell cylce
DNA tumor viruses are normally:
non-integrative
is a tumor virus' genome were to accidentally integrate into the host genome,
the viral genome would be constitutively expressed
viral genome constitutively expressed =>
E7 and E6 proteins made
HPV's E7 protein binds to:
Rb => pulls it off E2F => S-phase genes expressed
HPV's E6 protein binds to:
p53 => degradation of p53 => cell cycle continues unabated
(normally, E7 and E6 are destroyed, but not if
the viral genome has integrated
polynoma virus =
exactly like HPV, except uses Tag protein rather than E7/E6
vaccine against the polynoma virus =
Gardasil
Gardasil is given to younger people because:
HPV cancer is dormant for many years, despite being infected via sexual activity
**sporadic cancers always lose:**
two critical **tumor suppressor pathways**
****p16 and ARF are encoded on:****
***the same locus***

- mutation in one => mutation in the other
the p16/ARF locus is frequently mutated in cancers =>>
automatic two hits
mutation of p16/ARF locus can be
inherited
Li-Frauman disease =
cancer e/w
most cancers arise:
spontaneously, in somatic cells

- NOT inherited
almost all cancers have a non-overlapping alteration in the:
ARF - Mdm2 - p53 pathway
nutlins bind Mdm2, compete for
p53

- to stop p53 in cancer cells
MT's are highly
dynamic
dynamic instability of MT's, 4 stages:
assembly => catastrophe => disassembly => rescue
which end of MT's is anchored to the centrosome?
the negative end
MT's are stabilized by the addition of which 2 proteins?
1. MAP's (MT-Associated Proteins)

2. Tau
Tau ~
Alzheimer's
**major function of MT's =
transport of intracellular storage
***2 kinds of MT transport proteins**
1. dynein

2. kinesin
dynein moves stuff to:
the minus end
kinesins move stuff to
the + end

(some exceptions)
dendritic MT's ~ non-uniform poloarity
+'s face opposite sides
what does the drug colchicine do?
blocks MT polymerization by blocking tubulin
Interphase ~
centrosome duplicated
anaphase A and MT's:

(2)
1. kinetochore MT's shorten

2. dynein moves chromosomes toward poles
anaphsae B and MT's:
check
anaphase and MT's:
spindles get shorter as chromatids are pulled father apart, while poles move in opposite directions
prophase and MT's:
mitotic spindles assemble
prometaphase and MT's:
spindles attach to kinetochores
metaphase and MT's:
spindles run the length of kinetochore to centrosome
telophase and MT's:
contractile ring forms
contractile ring =
actin + myosin
Intermediate Filaments:

(3)
1. ***no motoer proteins = no movement***

2. no polarity => low solubility

3. basic unit = tetramer
function of intermediate flimanets =
mechanical strength/structure
animals with soft bodies have lots of
intermediate filaments
8 tetramers form a rope-like sturcture; cross-section =
32 monomers
cytokeratins also called:
keratins or tonofilaments
keratin is present in:
ALL epithelial cells
keratins are made up of paired subunits:
1 acidic,

1 neutral or basic
keratins attach to:

(2)
1. desmosomes

2. hemidesmosomes
***mutated keratin =>
blistering/skin rips off

= epidermolysis bullosa simplex (EBS)
2 other examples of intermediate filaments:
1. neurofilaments

2. vimentin
vimentin is cross-linked to MT:

(2)
1. depends on MT's for its own structure

2. will collapse when MT's disassemble
nucleus transport: anything greater than _______ requires transport through __________
50 kDa;

nuclear pores
**everything that goes to the nucleus requires:
NLS
***which Ras-family GTP-binding protein regulates nuclear entry?***
**Ran**
what are the 3 major kinds of nuclear lamina?
A, B, C
***P'n of nuclear lamins =>
**breakdown of nuclear envelope**
***Hutchinson-Gilford Progeria =
***mutation in gene for lamin A***

=> premature ageing
cancer and an 18-wheeler:
you need a lot of wheels to come off before things get serious
****p53 is altered in:
***every cancer***

- it's not sufficient, but it's necessary for cancer
cause of most cancer is NOT
infection

- but mutation from the inside
4 different ways of achieving cancer:
1. genetic instability

2. abnormal proliferation

3. changes in adhesion/migration of cells

3. induction of new blood vessels (angiogenesis)
Ras => MAPK, and PI3K, =>
increase in proliferation via Cyclin D and c-myc
mutated Ras in a constitutively active state =>
abnormal proliferation
constitutive action of all the parts of the TKR pathway, whether through increased expressions or increased activity, =>
cancers
Mdm2 ~
checkpoint
reciprocal translocation in CML =>
BRC-ABL = novel oncogene, the Philly
fusion of BCR-ABL disrupts normal auto-inhibitory domain of ABL =>
constitutively-active kinase (ABL) => activation of many parts of TRK pathway => abnormal proliferation of cells => CML
Which drug targets the Philly chromosome specifically?
Gleevec
point mutations => resistance => Gleevec ineffective =>
relapse

==> another specific drug against new mutations, => remission
loss of Cdk control =>
abnormal proliferation
stimulation of VEGFR =>
angiogenesis
VEGFR =
vascular endothelial growth factor receptor
cancer occurs later in life b/c
mutations need to accumulate past the "break point"
inc. in heterogeneity of cancer cells => inc risk that you'll have:
a cell resistant to chemo

=> relapse
chemotherapy induces
apoptosis
EVERY cell in every *multicellular* organism has
apoptosis
6 features of apoptosis:
1. cell shrinks

2. organelles preserved

3. membrane blebs

4. chromatin condenses

5. DNA fragments

6. dying cells get phagocytosed
3 features of Necrosis:
1. cell shrinks

2. organelles break

3. *major* inflammation
apoptosis requires:
ATP,

and sometimes proteins synthesis
***apoptosis DOES occur in neurons;
we make twice as many neurons as we need during development

- we lose half of them as development progresses

- apoptosis is turned off after development ends
too much apoptosis =>

(3)
1. stroke, SC injury

2. neurodegenerative diseases

3. AIDS
too little apoptosis =>

(2)
1. cancer

2. autoimmune disease
(T-cells aren't eliminated)
Ced's ~
C. elegans apoptosis
Extrinsic/Death Receptor Pathway: immune cells =>
Fas L TNF => FLTNFR => recruits Caspase 8 => cleaves Caspase 3 => activation => apoptosis
***what's the quickest pathway to apoptosis?***
the extrinsic pathway
Intrinsic Pathway
BCL-2 family proteins regulate Cytochrome C => binds to Apaf-1 => bind to Caspase 9 => activation of Caspase 3 => apoptosis
in a healthy cell, Cytochrome C is necessary for
energy production
what do Bcl's do?
punch holes in the mit, allow Cytochrome C's to leave
what's the key trigger/committed step of the intrinsic pathway?
Cytochrome C release
**p53 can induce cell death by becoming active and
increasing the transcription of apoptotic proteins
***viruses can stop apoptosis of infected cells via:***
IAP's

(Inhibitors of Apoptotic Proteins)
to inhibit IAP's so that apoptosis can continue, the mit releases:
smac
caspase inhibitors can provide
neuroprotection from caspases
problem with giving caspase inhibitors for a long time:
may develop cancer
EM: the darker mit are being:
autophagocytosed
EM: Smooth ER is always near:
the glycogen rosettes
EM: multi-vesicular bodies =
late endosomes
EM: classic peroxisome =
medium gray with darker gray inside
EM: polysomes =
circular mRNA with ribosomes
Rhabdomyolysis =
destruction of skeletal muscle

=> myoglobin in the urine
Ketone formation is regulated by _____________, not _____________
mass action;

hormones
FA synthesis requires
NADPH
Platelets do NOT have a:
nucleus,

and just about no protein synthesis ability

- ***but they do have enzymes like COX***
Phalloidin stabilizes:
F-actin
Krebs is located in the:
***mit. matrix***
Beta-2 integrins ~
inflammation
proteins destined for the ECM are
made on RER
what activates the light chain kinase of nonmuscle myosin?
calcium
genome instability ~
new mutations acquired much more rapidly
when insulin’s not around, proteolysis occurs => AA’s for GNG

- but are those AA's used by the skeletal muscle itself?
yes.
PPaRalpha =
a TF

- so is PPaRy
malonyl CoA inhibits
CPT-1
FFA's contribute to insulin resistance in liver and muscle because they:
block the TKR cascade.



- MAPK and PKB not stimulated as they should be => dec. in their effects

(see Sheet)
Cyclin D is the only cyclin that responds to:
extracellular GF's
cholesterol is synthesized from HMG CoA in the
cytosol

(80% in the liver)
the S phase releases ___________ to drive cycle from G1 to S phase
active Cdk2
P'd p53's =
Mdm2 NOT attached => high p53
inc Mdm2 = dec. p53 =
dec tumor suppression
***c-myc =
TF for cell growth => proliferation

- stimulated byTKR pathways
constitutively-active Ras => over-activity of:
c-myc and Cyclin D