Unit 2 Flashcards
How do cells harvest energy?
- glycolysis
- krebs cycle
- pyruvate oxidation
- etc and chemiosmosis
How does glycolysis harvest cell energy?
- not efficient
- doesn’t require O2
- all cells can do
How does pyruvate oxidation harvest energy?
conversion of pyruvate to acetyl co a
How does the electron transport and chemiosmosis generate energy for the cell?
- sometimes ETC is leaky and could be used from other processes so we don’t know exact number of ATP formed
- most efficient in prokaryotes because they don’t need to transport across mitochondria
Where is the electron transport chain done?
outer plasma membrane mitochondria membrane
What are the glycolysis substrates and products?
substrate: glucose
products: ATP, electron carriers (NADH), pyruvate which then goes to ACA
What does the electron tansport do?
turns glucose do into CO2
What do electron carriers do?
- produce ATP with ATP synthase
What is the order of energy formation in cells?
- glycolysis
- pyruvate oxidation
- krebs
- etc
Where do pyruvate oxidation and krebs cycle take place?
- mitochondrial matrix
Where does glycolysis take place?
in cytoplasm
What is the rate limiting step in glycolysis
PFK1
- takes the longest
What is the electron acceptor in glycolysis?
- NAD+
NaD+ oxidized
NADH is reduced
What is pyruvate?
- a 3 c molecule converted to ACA under aerobic conditions
What does pyruvate dehydrogenase do?
catalyzies pyruvate oxitation
Do tumors want to undergo pyruvate oxidation?
no
they want to turn it off so it can’t mutate and be detected
What happens to pyruvate under anaerobic conditions?
- converted to lactate/ lactic acid
- releases ethanol and acetylaldehyde
Where does the citric acid cycle take place?
- mitochondrial matrix
What is the citric acid cycle?
- biochemical pathway of 9 steps
- releases Co2
- reduces electron carriers
What are the substrates and products of the citric acid cycle?
- substrate is ACA, produces ATP, NADH, FADH2, releases Co2
- produces 1 atp per pyruvate or 2 per glucose
What are the electron carriers in the citric acid cycle?
- NADH FADH2
Do tumors want to undergo the citric acid cycle?
no
What is the electron transport chain?
- series of membrane bound electron carriers
- electrons from NADH and FADH2 are transfered to complexes of ETC
- creats an H ion gradient between 2 mitochondrial membanes during ATP synthase
What is NADH dehydrogenase?
- 1st complex in ETC
- accepts NADH
- not mutated in cancer
Do tumors want to undergo the citric acid cycle?
no
What is ATP synthase?
- has rotor with ADP and P
- as the H ions come down concentration gradient it rotates
- exposes ATP binding sites
- ## synthesizes ATP
What is chemiosmosis?
- H+ funnel taking H down concentration gradient to the matrix
- ADP and P are exposed to bind
How are cells regulated?
- phosphorylation
- ligand binding
- substrate availability
- metabolic re-programing
Why do cells need to get rid of pyruvate?
because its toxic and high levels and wee need it to generate electron acceptor
What does hexokinase do?
- helps cordinate glycolysis with tca cycle
- all activity is increased
What does hexokinase do in cancer cells?
- acts as a transcription inhibitor
- breaks down fructose and manose
- involved in first enzymatic reaction in glycolysis (also called gly1)
- mutated so glycolysis can’t be coordinated with TCA cycle
What does negative feedback of glycolyiss and gluconeogenesis do?
- product inhibits upstream production
- allows for self regulation and stops wast to increase efficiency
What are the three main regulatory steps of glycolysis?
- hexokinase
- phosphofructo kinase
- pyruvate kinase
What does kinase do?
phosphorylates
What does phosphotase do?
- dephosphorylates
What happens when PFK2 is not phosphorylated?
- activates glycolysis by making PFK1 pfk1
- catalyzes phosphorylation of F6p to F26BP
What happens if F26bp is added to glycolysis?
pfk1 is more active
What does low atp in glycolysis do?
drives pfk1 to act faster
What is the Warburg Effect?
- cancer ramps up glycolyiss, its main source of ATP for the cell
- helps cells avoid the mitochondria
- cancer has extra glucose transports
- activates pentose phosphate pathway
Why do cancer cells avoid the mitochondria?
- mitochondria has apoptotic proteins
Why does cancer have extra glucose transporters?
- now takes up (steals) glucose from healthy cells making them more susceptible to mutations
What does the pentose phosphate pathway do?
- produces NADPH
- protects cells from ROS (oxidizing agent bad for cell)
- mitochondria doesn’t know what to do with NADPH
- alternastive pathway to glycolysis
- produces ribosome
- ## doesn’t use pyruvate
What controls if cell can do aerobic or anaerobic processes?
h1f1
What does inhibited Beta oxidation do?
- turn fatty acids into ACA
- gets rid of ACA becasue its used in gluconeogenesis
- cancer cells don’t do gluconeogenesis so you need this turned off
- would inhibit future beta oxidation
What are the cell cycle checkpoints?
- G1-M transition
- Metaphase anaphase transition
- GO restriction pt
- very likely more
What is the G2-M transition influenced by?
- cell size, DNA damage, DNA replication
What is metaphase anaphase transition influenced by?
- chromosome attachements to spindle
What is the g0 restriction pt influenced by?
growth factors, nutrients, cell size, DNA damage
What cells don’t typically go through the G0 restriction point
cells that don’t typically divide
- brain cells, stem cells, heart cells
What does active CDK stimulates?
- nuclear envelope breakdown
- chromosome condensation
- mitotic spindle formation
- targeted protein deregulation (degrades membrane and extra intracellular pathogens)
What happens if spindle fibers weren’t securely attached to it?
it would lead to incorrect chromosome number?
- this gets worse as we age
What is prophase?
chromosomes form
spindle fibers form
nuclear membrane begins to form
What is metaphase?
chromosomes in center
spindle fibers attach to centromere
What is anaphase?
- chromatids split, go to opposite sides
What is telophase?
- new membranes form
- spindle fibers disappear
What is interphase?
DNA replicaiton
What does F26BPase do?
- acts on kkinases just like pfk2 except it moves the cell away from glycolysis
- main mechanism for regulating glycolysis
How does F26BP activate glycolysis?
- allosteric activator
- activates PFk1
- high PFK2 increases F26BP levels leading to more PFK1 activation leading to glycolysis
0
What does CAMP do with F26BP
- loweres levels of F26BP to reverse increase in glycolysis
What does F26BP do?
- activate glycolysis or inhibit gluconeogenesis
What is AKT?
- protooncogene
- supresses apoptosis
- promotes cell growth
How is AKT activated
phosphorylated
What does BAD do when phosphorylated?
- inhibits apoptosis even if there is DNA damage
What is the difference between apoptosis and necrosis?
- apoptosis is controlled mechanisms that forms pieces ready to be digested and recycled
- necrotic death is uncontrolled and could damage surrounding cells
What do viruses infecting cells do?
- triggeres TNFalpha to bind recruiting t-cells to destroy the cells
- triggeres increase in CD95 receptor proteins to recruit adaptor proteins
- executioner pathway activated
- initiator caspase is inactive unless triggered by ligand
What happens if an initiator caspase is triggered by a ligand?
- activated executioner caspase
What do executioner caspases do?
- destroys cell
- forms apoptotic bodies
How does the absence of survival/ growth factors cause cell death
- pro-apoptotic proteins are inserted into the mitochondrial membrane and release cyt c
- cyt c then triggers Ca2+ release from ER by binding to IP3 receptor and activate procaspase forming apoptosome
- additional antiapoptiotic proteins in a healthy cell
What are the pro-apoptotic proteins?
BAX
BAK
BAD
What are the BCL2 family apoptotic proteins?
- BAX
- BAD
- BAK
- BH3
When does an absence of survival/ growth factors typically happen
- embryonic development and possibly aging cells
What are Bax and Bak associated with?
viral apoptosis
What is BH3 and BAD associated with?
survival factors
What does BAD cause?
- BCL2 associated apoptotic death
- binds BCL2 and BCLXL, inactivating its anti-apoptotic mechanisms
What happens if BAD is phosphorylated?
- it loses its ability to bind and then becomes anti-apoptotic
When are pro-apoptotic proteins released?
after releasing CYT C and activating caspase
What are the anti-apoptotic proteins?
BCL2 and BCLXl
What do anti-apoptotic proteins do?
- inhibit CytC release and caspase activation
What are the cell death pathways?
- executioner: death receptor, initiator caspase with incorporated death receptor, executioner procaspase to executioner caspase to apoptosis
- no survival factors: no survival factors to death promoting proteins to CYT C to initiator procaspase to apoptosome with initiator caspase to executioner procaspase to executioner caspase to apoptosis
- dna damage: damage to P53 to death promoting proteins to cyt c to initiator procaspase to apoptosome with initator caspase to executioner procaspase to executioner caspase to apoptosis
What happens if there is a mutated executioner or initiator?
no apoptosis leading to cancer
What happens if FAS is mutated?
- can’t bind to immune cells = no apoptosis = cancer
What part of the cell cycle is the anaphase promoting complex in?
- m phase
- part of MA transition
What part of the cell cycle is the mitotic CDK in?
M phase
G2
What part of the cell cycle is inactivated mitotic cyclin in?
g2 phase
What part of the cell cylce is active mitotic CDK cyclin in?
- G2-M transition
- MA transition
How is mitotic cyclin and cdk activated?
- mitotic cyclin is added to a phosphorylated CDK
What does phosphorylated AKT do?
- activates BAD, phosphorylated bad would then inhibit apoptosis
- activates RHEB to TOR to activate cell growth
What dows an activated PI3K do?
- activates a phosphorylated AKT
What are the three ways to stop damages DNA?
- checkpoint kinases going to unphosphorylated P53 leasing to degredation
- checkpoint kinase to phosphorylated kinase to p21 (CDK inhibitor) inhibiting CDK Cyclin complex then leading to cell cycle arrest due to no phosphorylated RB protein
- checkpoint kinase to phosphorylated P53 to PUMA (BCL binding proteins) inhibiting BCL2 leading to apoptosis (inhibition of an apoptosis inhibitor)
What is the main mechanism of G1
- growth factor activates ras pathway triggering CDK cyclin leading to the disconnect of E2F and RB after RB is phosphorylated then leading to gene transcription and mRNA translation
- atp is still needed
What must happen for anaphase promoting factor to be active?
- anaphase promoting factor isn’t active until all replicated chromosomes are attached and all chromatids are attached to each other
How is active APC formation inhibited until it is ready?
madbub is bound to the cromatids
How does the anaphase promoting complex work?
- once spindle fibers are attached mad bub disengages and binds to cyclin
- the active APC then degrades mitotic cyclin
seperase enzyme is bound to securin to inactivate it, but active apc degrades securin allowing securase to degrade cohesion allowing chromatids to split
What must be present for the m to G1 transformation, and g2 m transition
- mitotic promoting factor activing and mitotic cyclin
When does mitosis start?
g2 m transition
How does the mitotic cdk cyclin complex become active?
- When mitotic Cdk and mitotic cyclin come together they form an inactive complex
- the phosphate croups attached to the CDK by inhibitory kinases inhibit them
- activating phosphate groups then add an activating kinase but as long as an inhibitory phosphate is still present it is still inactive
- once a phosphatase removes the inhibitory phosphates the complex is active and continually stimulates more phosphatase
