Exam 4 - Cell Cycle, Apoptosis, Regulation Flashcards
What stage does the dividing cell leave the cell cycle?
G1
In rapidly dividing embryonic cells, dominant stage in cell cycle?
M + S
cyclin with increased concentration after interphase
cyclin B
cyclin present in most stages of cell cycle
cyclin D
restriction point characteristics
within G1
commits cells to divide
makes cell insensitive to mitogens beyond this point
G1 checkpoint in animals
R point
modes of CDK regulation
interaction with CDK inhibitors
ubiquination of cyclins
phosphorylation of CDKs
begins cyclin ubiquination
cyclin destruction box
most frequently mutated protein in human tumors
p16
p21 mode of CDK inhibition
bind to active site
INK4 mode of CDK inhibition
replace cyclin
result of Cdc25 deficit and Wee1 excess
elongated cells
increased G2 phase
activates Cdc2
Cdc25
inhibits Cdc2
Wee1
Wee1
inhibits Cdc2
prolongs G2
result of Wee1 deficit and excess Cdc25
small cells
decreased G2 Phase
chemical modification mediating cyclin destruction
ubiquitination
most important checkpoints in cell cycle
G2-M
G1-S
effect of CDK inhibitor on cell cycle
disrupts G1-S transition
mechanism of INK4 family as inhibitors
disrupt association of cyclin with CDK
characteristics and features of apoptosis (10)
activation of caspase in cytoplasm activation of nucleases in nucleus occupation of death receptor on membrane release of cyt c from mitochondria dimerization of Bcl-2 family translocation of phosphatidylserine ATP dependency internucleosomal DNA fragmentation (ladder pattern) absent at 4-deg no inflammation cell shrinkage membrane blebbing lamin breakdown phosphorylation of bad protein(?)
caspase where extrinsic and intrinsic caspase cascades converge
caspase 3
pyknosis
nuclear shrinkage
DNA condenses
(during apoptosis)
karyolysis
nuclear fading
chromatin dissolution from nucleases
(during apoptosis)
karyorrhexis
nuclear fragmentation
pyknotic nuclear membrane ruptures and fragments
(during apoptosis)
karyokinesis
nuclear division
during cell division
effect of c-Myc
increases apoptosis
reduces tumor growth
no effect from loss of function mutation of one of its alleles
serum and urine osmolarity in distended bladder (1L H2O intake)
serum: 250 mmOsm/L
urine: 100 mOsm/L
baroreflex mechanism
baroreceptors are stimulated
medullary constriction center is inhibited
vagal parasympathetic system is excited
net effect of vasodilation and lower heart rate and strength of contraction
estimated fluid volume in interstitial compartment of a 50kg male
7.5 L
interstitial fluid = 15% BW
total body water
60% BW
ICF volume
40% BW
ECF volume
20% BW
plasma volume
5% BW
ISF volume
15% BW
osmotic pressure
pressure needed to prevent movement of water from area of high water concentration to area of low water concentration
counteracting mechanism to decrease in effective circulating volume
increase rate of Na+ retention
effect of lower effective circulating blood volume on ADH
increased ADH release
renal sodium and fluid retention
effect of stimulation of low pressure stretch receptors
increase release of atrial natriuretic peptide (from heart)
primary regulator of sympathetic nervous system
rostral ventrolateral medulla
factors increasing salt and water excretion
↓ sympathetic response
↓ ADH
↑ ANF
main regulator of sodium excretion
aldosterone
impermeant solutes
mostly electrolytes (Na, Cl, K)
examples of permeant solutes
glycerol, urea
causes anisosmotic volume change
alterations in extracellular osmolality
causes isosmotic volume change
change in intracellular osmolality
low pressure strectch receptors
cardiac atria receptors
cardiopulmonary receptors
effect of stimulation of cardiac atria receptors
increased release of ANF
increased neural impulses from hypothalamus to medulla
reduced sympathetic neural discharge to kidney and ADH secretion
increase in salt and water excretion by kidney
provides stimulus for earliest release of ADH
increase in plasma (ECF) osmolarity
cause of isosmotic change in cell volume
increased ICF osmolarity
can be caused by head trauma, stroke
effect of drinking urine
increase in effective circulating (plasma, ECF) volume
dehydration
correction treatment priority for dehydrated survivor
intravascular volume
threshold for thirst
295 mOsm/L
manifestations of plasma/intravascular volume depletion
low BP
rapid pulse
manifestations of interstitial volume depletion
poor skin turgor
dry tongue
sunken eyes
manifestations of ICF volume depletion
hallucinations
disturbance of function
concentration determining steady state volume of cell
extracellular impermeant solutes
mechanism protecting brain from rapid increase in plasma osmolarity
electrolyte gain
converts prothrombin to thrombin
Factor Xa
converts fibrinogen to fibrin
thrombin
catalyzes hydrolysis of fibrin
plasmin
activated by tissue thromboplastin/factors
extrinsic pathway
activates extrinsic pathway
tissue thromboplastin/factor
activated by contact with certain surfaces (e.g. collagen)
intrinsic pathway
activates intrinsic pathway
contact with certain surfaces such as collagen
mechanism of heparin as anticoagulant
interferes with final common pathway of coagulation
The immune system exhibits tolerance to both self and non-self molecules. T/F?
T
The core function of the immune system is destruction of non-self molecules. T/F?
F.
Some non-self molecules such as food and fetus are tolerated.
Most antibodies are normally coded for by unmodified germline DNA sequences. T/F?
F.
Most antibodies arise from modification of germline DNA.
Both heavy and light chains determine antibody class. T/F?
F.
Only the constant region of the heavy chain determines antibody class.
Only the heavy chain contributes to antigen binding by antibodies. T/F?
F.
Both heavy and light chains contribute to antigen binding by antibodies.
IgA normally crosses the placental barrier. T/F?
F.
IgG can cross placental barrier, not IgA.
IgM normally constitutes the majority of circulating antibodies in plasma? T/F?
F.
IgG is most abundant in plasma.
IgG normally appears in primary response to first exposure to an antigen. T/F?
F.
IgM is responsible for primary response to first exposure.
constitutes majority of circulating antibodies in plasma
IgG
first to appear in primary response to first exposure
IgM
Ig capable of crossing placenta
IgG
endotoxin from Gram negative bacteria
lipopolysaccharide (LPS)
main function of lysozymes
catalyze hydrolysis of bacterial cell walls
cytokines
non-antibody molecules regulating immune function via auto/paracrine signals
chemokines
specialized cytokines
attract leukocytes and promote endothelial adhesion
phagocytes
neutrophils
macrophages
monocytes
hallmark of inflammation
increased vascular permeability
Activation of complement pathways contibutes to opsonization. T/F?
T
Class I MHC location
most nucleated cells
Class I MHC role
present fragments of endogenous protein antigens (from APC)
enable recognition of antigens by cytotoxic T cells
coreceptor on cytotoxic T cells for antigen recognition
CD8
cytotoxic T cells
destroy targets by inducing apoptosis
coordinate adaptive immune responses
immunization requiring actual antigen exposure
active immunization
principle underlying most vaccination schemes
active immunization
example of passive immunization
maternal antibody transfer
Blood-group antigens include MHC proteins. T/F?
F
MHC antigens include blood-group antigens. T/F?
T
HLAs are blood-group antigens. T/F?
F.
It is an MHC antigen.
stimulate cell-mediated killing by cytotoxic T cells and macrophages
Th1 cells
stimulate antibody production by helping B cells
Th2 cells
stimulate immune responses against extracellular pathogens
Th17
mechanism of cyanide poisoning
hypoxic cellular damage
blocks cell enzyme action (cytochrome oxidase of mitochondria)
effects of cell hypoxia
increased production of lactic acid and inorganic phosphates
decreased cell pH
consequences of decreased IC ATP cell injury
ER swelling cellular swelling loss of microvilli blebs clumping of nuclear chromatin lipid deposition
effects of inhibition of Na-K-ATPase pump
apoptosis
influx of Na+ and Ca++ (also H2O)
efflux of K+
ER and cellular swelling, loss of microvilli, blebs
changes due to ischemia
decreased glycogen
decreased oxidative phosphorylation
decreased ATP
increased anaerobic glycolysis
Because of interdependent nature of cellular systems, damage to one part may result in secondary injury to other systems. T/F?
T
Cell injury results from functional and biochemical abnormalities in one or more essential cellular components. T/F?
T
Biochemical and morphological manifestations of injury are usually seen first before loss of cellular function. T/F?
F
loss of cell function -> biochemical manifestations -> morphological manifestations
cell’s ability to achieve new steady state compatible with viability in environment
adaptation
major mechanisms for electrical injury
disruption of cell membranes alteration of biomolecular conformation change in RMP eliciting muscle tetany converting electrical energy to heat mechanical injury from direct trauma caused by abnormal contraction-relaxation
causes injury from ionizing radiation
free radical formation and breaking of chemical bonds
mechanism of cell damage from extreme cold
formation of crystals that puncture cells
slow metabolic activites to near/total cessation
mechanism of cell damage by rheumatic fever
inflammatory/immune response injuring cardiac cells
example of physiologic atrophy
post-menopause uterine atrophy
cells commonly affected by hypertrophy
non-dividing cells such as cardiac and skeletal muscles
effect of hypertrophy
increase in cell size
increased functioning tissue mass
example of metaplasia
Barrett’s esophagus
- normaly columnar epithelia is replaced by squamous epithelia
hyperplasia
increase in total number of cells
metaplasia
reversible change in cell structure due to noxious stimulus
dysplasia
abnormal cell growth with disordered cellular morphology, organization, and function
pathologic
hypertrophy
increase in cell size
cellular dysplasia
always pathologic
precursor to cancer
disordered cell morphology, organization, function
abnormal cell growth
secondary organ following bone marrow dysfunction
spleen
RBC in anemic patient
hypochromic
microcytic
common blood lines in normal bone marrow
erythropoeisis
granulopoeisis
ABO blood type with most antibodies in plasma
O
most accessible site to perform bone marrow biopsy in adult
pelvis
central executioner for apoptosis
caspase
role of insulin in homeostasis
efferent pathway
effect of steroid hormones
positive feedback of hypothalamo-pituitary tract axis
increase in LH, FSH, testosterone
neurotransmitters derived from tyrosine
epinephrine
norepinephrine
thyroxin
body’s response to low intravascular volume and high serum osmolarity
increased ADH
stimulation of sympathetic nervous system
indirect acting toxic substance
needs to be metabolized by body to produce toxic metabolite
e.g. acetaminophen/paracetamol
state in which cell milieu is within narrow range or physiologic parameters and cells is able to maintain normal structure and function
homeostasis
apoptitic pathway
triggers -> modulators -> effectors -> substrates -> DEATH
triggers of apoptosis
loss of GF loss of O2 loss of adhesion activation/occupation of death receptors radiation and chemotherapy
modulators of apoptosis (7)
FADD, TRADD, FLIP
Bcl-2 family and cyt c
p53, Mdm2
effectors of apoptosis
caspases
proteins which degrade other proteins
caspases
inactive caspase precursors
procaspases
results in irreversible breakdown of nuclear membrane
cleavage of lamin proteins
effect of Ras
increases tumor growth
reduces apoptosis
viruses inhibiting caspases
CrmA
baculovirus p35
Ebstein Barr Viruses
increased Bcl-2
usually means poor prognosis
determines chemosensitivity
FasL induction with Doxorubicin
hallmarks of cancer (12)
self-sufficiency in growth signals insensitivity to anti-growth signals tissue invasion and metastasis limitless replicative potential sustained angiogenesis evading apoptosis oxidative stress DNA damage mitotic stress proteotoxic stress metabolic stress evading immune surveillance
longest phase in the cell cycle
interphase
what happens in G1?
organelle duplication without DNA replication
what happens in S phase?
semi-conservative DNA replication
protein joining sister chromatids
cohesin
what happens in G2?
formation of mitotic spindle
increase in cellular content
what happens in M phase?
mitosis and cytokinesis
stages of mitosis
prophase: chromatin -> chromosome
prometaphase: x nuclear membrane, / kinetochores
metaphase: chromosomes in the middle
anaphase: chromosomes to opposite poles
telophase: cytokinesis, chromosome -> chromatin
requirements for chromosome transmission
only one centromere
functional telomeres
chromosomes fully replicated
chromosomes adequate size
drives cell cycle
CDK
CARD 153! Congrats on reaching this far!
I have no more Biochem jokes, but make sure to SMIIILE! =D
Studying is fun! #mantra
number of CDK targets in humans
292
activate CDK
cyclin
cyclin in G1-S transition
cyclin E
cylcin A - more in S phase
cyclin in M phase entry
cyclin B
cyclin binding early to mid-G1
cyclin D
regulation of CDK
cyclin synthesis and destruction
phosphorylation
binding to CKI (inhibitory proteins)
controls cyclin destruction
ubiquitination
cyclin destruction box
mitotic phase with highest cyclin B
metaphase
mitotic phase with lowest cyclin B
telophase
DNA damage checkpoints
late G1
S phase
G2 checkpoint
between G2 and M phases
requires complete DNA synthesis
spindle assembly checkpoint
between metaphase and anaphase
requires complete chromosome-spindle attachment
prolonged G1 state
G0
most frequently mutated CKI in human tumors
p16
mutant proto-oncogenes
oncogenes
role of p53
tumor suppressor
triggers apoptosis of damaged cells
What did the french biochemist do with his twins?
He baptised one and saved the other for a control.
@@ Kaloka.
Done with this batch. Good luck sa’tin! =D
