biochem lecture 4 pt 2 Flashcards
what happens when there’s no O available
in order for cell to generate ATP in absence of oxygen there is a need for NAD+ (oxidized NAD)
what serves as an electron acceptor in redox rxn for G3P to 1,3-BPG
NAD+ (oxidized NAD)
what do we generate after NAD+ accepts electron
NADH
what is goal of fermentation
to regenerate NAD+
why is the goal of fermentation to generate NAD+
without that glycolysis won’t be able to continue
what happens to everything in the absence of oxygen
shut down TCA, ETC, ox phos
what happens to electrons in absence of O
no place for electrons to be donated to; no electron acceptor
basically what happens if no O2 available to keep redox balance
everything backs up and stops
what are fermentation reactions a way for
maintain redox balance so that you don’t have accumulation of NADH and everything stops
what happens if redox balance is disrupted
stuff accumulates and later stops
why does glycolysis continue when TCA cycle and ETC shut down
because in fermentation reactions you generate oxidized NAD+ which allows glycolysis to keep going
define fermentation
energy extraction (like ATP formation thru substrate level phosphorylation) w/o oxygen consumption
is there a net change in [ ] of NAD+ and NADH in fermentation
nope
basically what is fermentation
means by which ATP production (primarily thru substrate-level phos) occurs without consumption of oxygen
what happens cuz there’s no final electron acceptor in absence of oxygen
we are maintaining some redox balance by transferring electrons from NADH to something else
how do we maintain the redox balance in absence of oxygen
by transferring electrons from NADH to something else
what is that “something else” (that we transfer electrons from NADH to)
usually a product that’s generated at end of fermentation pathway –> ethanol or lactate
basically how does fermentation maintain redox balance
by transferring electrons from NADH to ethanol or lactate
describe lactic acid fermentation
conversion of glucose to lactate
how many steps in lactic acid ferementation
one step process
when does lactic acid fermentation occur
when we have oxygen depletion in muscle in mammals (extended muscle contraction)
what happens despite oxygen being depleted
doesn’t change the fact that muscle needs ATP E; just needs from a diff source
basically where is the ATP that muscle needs coming from (in short erm)
in lactic acid fermentation step
how many redox reactions in lactic acid fermentation
2 redox reactions
is there a net change in oxidation state of carbons in glucose
nope; same H:C ratios for glucose and lactate
is there energy extracted in conversion of glucose to lactate
yup; 2 ATP per glucose
describe what happens to pyruvate at end of glycolysis in lactic acid fermentation
pyruvates at end of glycolysis are gonna be used in a redox reaction that oxidizes NADH to NAD+, and reduces pyruvate to lactate
what is the issue after glycolysis
NAD is reduced to NADH
what do we need to do to keep glycolysis going
find a way to oxidize NADH to NAD+
why do we say there is no net change in [ ] of NAD+ and NADH (oxidized vs. reduced NAD)
because the cell just cycles back between oxidized and reduced forms (basically we’re carrying out cyclical redox reactions involving NAD)
what enzyme in lactic acid fermentation
lactate dehydrogenase
what does fermentation allow for
regeneration of NAD+ (oxidized) in order to extract energy (ATP) from glucose; no net change in [NAD+] and [NADH]; same ratios
what is the biggest takeaway in fermentation
need to regenerate NAD+
what happens without NAD+
we can’t continue glycolysis
why is there no net change in NADH vs NAD+
b/c its just cycling b/w reduced and oxidized forms
what does oxidizing to NAD+ allow
keeps glycolysis going, enable cell to keep generating ATP in absence of oxygen
which generates more ATP, glycolysis (fermentation) or cell respiration
cell respiration by a lot, but still
describe fermentation as a solution
short-term solution
what happens in the long run
we will need oxygen at some point
describe ethanol fermentation
two steps, converts pyruvate –> acetaldehyde –> ethanol
what is first enzyme in ethanol fermentation
pyruvate decarboxylase
what does pyruvate decarboxylate do
pyruvate –> acetaldehyde; carries out a decarboxylation rxn where we release one of the Cs from pyruvate in the form of CO2
what does decarboxylation do
generates acetaldehyde intermediate
what is second enzyme
alcohol dehdyrogenase
what happens to acetaldehyde intermediate
goes thru redox reaction
describe alcohol dehydrogenase
same as lactate dehydrogenase
what does alcohol dehydrogenase do
regenerates oxidized NAD (so NAD+) ***CRITICAL STEP and reduces acetaldehyde to form ethanol
do lactic acid and ethanol fermentation have the same goals
yup; to reoxidize NAD so it can be fed back into glycolysis and keep it going
what does anaerobic fermentation lead to
production of 2 ATP/glucose
what does ox phos yield
up to 38 ATP/glucose
who gives more
ox phos (cell respiration)
what did Pasteur discover
yeast consumes a lot more glucose vs/ yeast grown in oxygen
pasteur effect
yeast cultures grown anaerobically are able to consume glucose via glycolysis a lot more glucose compared to aerobically
why do anaerobic yeast cultures consume more glucose
ramping up of glycolysis is a way of maintaining the same level of ATP in cell under anaerobic conditions vs aerobic
how do cells generate same numbers of ATP in absence of oxygen
by ramping up glycolysis; increasing production of glycolytic enzymes, increasing rate & level of glycolysis in cell
so who has more glycolytic activity
anaerobic conditions
what is pasteur effect
yeast consume more sugar when grown under anaerobic conditions
who has faster rate of ATP production
anaerobic glycolysis, up to 100x faster than ox phos (but uses way more glucose)
on an absolute scale who has more ATP
anaerobic glycolysis, but number of ATP per glucose is same (we also use more glucose)
who has more ATP per unit
both have same; 2 ATP per glucose
basically what is pasteur effect
we are increasing expression of enzymes that carry out steps of glycolysis
how is it the same ATP per unit
we feed more glucose into glycolysis
what 2 enzyme deficiencies affect enzymes that are in glycolytic pathway
hexokinase deficiency and pyruvate kinase deficiency
what step is hexokinase
first step
what step is pyruvate kinase
last step
what do both of these deficiencies do
affect our ability to transport, carry, deliver oxygen to tissues
what is responsible for oxygen transport & deliveries
red blood cells
why are red blood cells responsible
cuz they have a lot of hemoglobin
what is hemoglobin
oxygen binding protein
what is hemoglobin structure
tetrameric structure so its affected by allosteric mechanisms
where does the link between hemoglobin and glycolysis come from
an intermediate; 1,3-BPG
what does BPG have an effect on
hemoglobin’s affinity for oxygen
where does BPG bind to hemoglobin
central portion of tetramer of hemoglobin (where the 4 subunits meet)
what’s at the central portion
a lot of salt bridges, electrostatic interactions
what is result of BPG binding to hemoglobin
perturbs salt bridges, lowers hemoglobin’s affinity for oxygen
describe BPG in normal conditions
BPG is an important player in facilitating dumping of oxygen into tissues that need it from hemoglobin
what do these two deficiencies do to BPG
altered levels of BPG
what does hexokinase do
reduced ATP and BPG production
describe hexokinase deficiency
can’t convert glucose to G6P, since 1,3-BPG formation occurs after this step, if first step can’t occur then 1,3-BPG is not formed
what does less BPG to do hemoglobin’s affinity for oxygen
BPG binds to hemoglobin and lowers its affinity; less BPG increases hemoglobin affinity
what happens w/ increased hemoglobin affinity
hemoglobin needs to bind AND release oxygen; if too much affinity it can’t release oxygen
basically what does less BPG do
greater affinity for oxygen, and thus harder to release
what kinda protein is hemoglobin
allosterically regulated protein
what kinda curves do we associate hemoglobin with
sigmoidal curves
what does oxygen binding to hemoglobin do
influences the affinity of binding of subsequent oxygens to other 3 subunits of tetramer
what curve associated w/ protein allostery
sigmoidal curve
sigmoidal curve is specifically associated with what
cooperativity allostery
what are cooperative effects
if we have a binding of ligand, it binds to 1 of 4 subunits. transmits conformational changes in tetramer that leads to elevation/increase in affinity of binding oxygen to other three subunits.
what is increase in affinity further increased with
each oxygen that binds
describe middle trace
normal; shallow slope
what happens to slope as you increase [ ] of oxygen
steepens a lot til it levels off
what happens in hexokinase deficient individuals
lowers BPG; increases affinity; leftward shift in curve
what does leftward shift mean
increased affinity (achieve same percent at lower value)
rightward shift
lowering of affinity (achieve same percent at higher value; takes more to achieve the same)
what is pyruvate kinase deficinecy
block occurs after step of BPG forms; buildup. concentrations of intermediates will increase, so more BPG
what happens to BPG levels in pyruvate kinase deficient ppl
higher levels of BPG
what does more BPG do
lowers hemoglobin’s affinity for oxygen
what happens in both cases
problems in ATP production; reduction in O2 delivery, but for diff reasons
hexokinase
hemoglobin has too much affinity, hangs on to O very tightly, not much will be dumped off
pyruvaye
don’t have enough O binding to begin with, so less is delivered
what do tumors have more of
enhanced glucose uptake & glycolysis rates
glucose uptake correlated w/
tumor aggressiveness and poor prognosis
what happens to cancer cells
grow more rapidly than blood cells that nourish them; starved for oxygen, need ATP
why do tumors have increased glycolytic capacity
uncontrolled cell division, need more ATP to carry out processes
what happens in tumors
hypoxia
what is hypoxia
low levels of oxygen
HIF 1
hypoxia inducible transcription factor
how are tumor cells clever
can adjust to hypoxic conditions
what does HIF 1 do
increase expression of glycolytic enzymes as well as various glucose transport proteins
GLUT
example of glucose transporter
what do tumor cells do under hypoxic conditions
increase rate of glucose uptake and rate of glycolysis
what does increasing glucose uptake and glycolysis allow tumors to do
enables these oxygen and nutrient starved tumor cells to keep growing and dividing
what else does HIF-1 do
increases expression of VEGF
VEGF
vascular endothelial growth factor
what does VEGF do
stimulates vascularization within the tumor
what does VEGF increase
angiogenesis
what does tumor need as it grows
needs a way to increase nutrient uptake and ATP
how does VEGF increase nutrient uptake
VEGF released by tumor cells stimulates vascularization or blood supply to growing tumor
what is VEGF triggered by
HIP-1
angiogenesis
formation of blood vessels
warburg effect
tumor cells increase rate of glucose consumption (have increased metabolic activity, increased levels of glycolysis)
