biochem lecture 9 pt 1 Flashcards
glwhat molecules can be used to synthesize glucose via gluconeogenesis
pyruvate, lactate, etc.
gluconeogenesis
synthesis of glucose from non carbon precursors
what are glycolysis and gluconeogenesis
opposite pathways
what do both pathways have in common
reciprocally regulated
what do mammals require to sustain us
carbs
where do we get carbs
diet, glycogen stores (liver and muscle), gluconeogenesis
absorptive phase
immediate access of glucose from the things we eatt
post-absorptive phase
short term starvation conditions; we rely on glycogen stores to provide glucose source
what do we rely on for glucose in short-term starvation conditions
glycogen stores
what happens if we don’t get more glucose (no more from diet or we’ve depleted stores)
we begin gluconeogenesis
how does gluconeogenesis initiate/progress
initiates slowly overtime, gradually increases to sustain organ function
what happens when you go beyond intermediate starvation to prolonged starvation (many days)
we see decrease in gluconeogenesis
why is there decrease in gluconeogenesis after a while
cuz there is a lack of carbon skeletons necessary to provide glucose via gluconeogenesis
what do you need in order to sustain life
supplementation of carbs
main sources of glucose needed to sustain life
dietary/exogenous, glycogen stores, and gluconeogenesis
when are glucose stores depleted
periods of starvation, fasting beyond a day
gluconeogenes invovles
pyruvate –> glucose
how many pyruvates do we need to make 1 glucose
2 pyruvates
what is required
2 NADH, 4 ATP, 2 GTP
glucogenic molecule
any molecule that can be converted into pyruvate
examples of glucogenic molecules
lactate, AAs, glycerol
so what does that mean if a molecule is glucogenic
can derive gluocse from that precursors
what are glycerol again
backbone of neutral fats
what are bypass reactions
unique to gluconeogenesis
describe bypass rxns
diff enzymes that catalyze a step in glycolysis, deff enzymes catalyzing the reverse step
what are irreversible glycolytic enzymes
hexokinase, PFK, pyruvate kinase
what are enzymes of gluconeogenesis
pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphate, glucose-6-phosphate
what are irreversible steps in glycolysis
exergonic
what are these steps then in other drxn
exergonic
each of these bypass rxns enzyme catalyzes what
an exergonic step
are these steps reversible or irreversible
technically reversible, but its mostly unidirectional so irreversible
what is importance of having unique enzymes
is something is unidirectional, then we can’t have the same enzymes
in order to have each of those steps occurring in one direction, and not influenced by flux, what do you need
need a different enzyme
how are the 3 glycolytic and 4 gluconeogenic enzymes controlled
reciprocally controlled by same hormones insulin and glucagon
describe example of this reciprocal control
if you’re stimulating glycolysis, means that 3 enzymes that catalyze 3 exergonic steps are gonna be active, while simultaneous inactivation of gluconeogenic bypass rxn enzymes
what is understanding the importance of bypass rxns crucial force
understanding how we have reciprocal control in a seemingly reversible process (glycolysis vs. gluconeogenesis)
what are key points of regulation going to involve
these bypass reactions
what 4 enzymes are bypass reactions in gluconeogenesis catalyzed by
pyruvate carboxylase, phosphoenolpyruvate carboxylase, fructose-1,6-bisphosphatase, glucose-6-phosphotase
why is it 4 steps instead of 3
process for PEP to pyruvate conversion in glycolysis is one step BUT pyruvate to PEP is two step process (via formation of oxaloacetate)
what catalyzes the first step in pyruvate to PEP
pyruvate carboxylase
what catalyzes the 2nd step
phosphoenolpyruvate carboxylase
what enzyme catalyzes the bypass of pyruvate kinase
pyruvate carboxylase
what do carboyxlaes do
tack on carbons to structures
what do decarboxylases do
remove carbons from structure
what does pyruvate carboxylase do
addition of carbon in form of bicarbonate to pyruvate, generates oxaloacetate
what rxn does pyruvate carboxylase do
pyruvate –> oxaloacetate
what rxn (thermodynamically speaking) is pyruvate carboxylase catalyzing
exergonic or irreversible step
what cofactor requirement do carboxylases have
biotin
what activates carboxylase
acetyl CoA
what is acetyl CoA an indicator of
low E state in the cell;
what is acetyl CoA serving as low E indicator important for
important for catalyzing synthesis of glucose
what kinda rxn is this first bypass step
anaplerotic rxn
what is an anaplerotic rxn
rxns that replenish intermediates in a pathway
what is oxaloacetate synthesized for
final product in TCA: in order to keep eTCA going, we have synthesis of oxaloacetate thru this bypass rxn
what does the second enzyme do
oxaloacetate –> phosphoenolpyruvate
what enzyme for second one
phosphoenolpyruvate carboxykinase (PEPCK)
when does PEPCK synthesis increase
increases in fasting
where does first bypass step occur
pyruvate to oxaloacetate conversion is in mitochondrial matrix
where does second bypass step occurs
in cytosol
so what is needed in order for gluconeogenesis to occur
oxaloacetate needs to go thru interconversion steps involving malate formation
describe thermodynamics of pyruvate carboxylase
metabolically irreversible
what does pyruvate use as a cofacto
biotin
what is pyruvate carboxylase allosterically activated by
acetyl CoA
what kinda rxn is pyruvate carboxylase step
anaplerotic for TCA cycle
how is pyruvate carboxylase anaplerotic for TCA cycle
cuz it replenishes oxaloacetate for TCA cycle
where does pyruvate carboxylase step occur
mitochondria
what is biotin utilized by
carboxylase
how is biotin utilized
covalently associated to specific lysine residue in active site of carboxylase
what happens to pyruvate and where
pyruvate is carboxylated into oxaloacetate, by pyruvate carboxylase, in mitochondria
what is needed for pyruvate to enter gluconeogenic pathway
needs to enter mitochondrial matrix
how does pyruvate get into mitochondrial matrix
specific transporters
basically what is needed for pyruvate to go into TCA cycle
needs to get into mitochondrial matrix
what happens to pyruvate in mitochondria
converted to oxaloaecetate by pyruvate carboxylase
what happens to oxaloacetate in mitochondria
converted to malate
who does oxaloacetate –> malate
malate dehydrogenase
what does oxaloacetate to malate conversion allow for
export of carbon skeletons originally derived from pyruvate back into cytosol from mitochondrial matrix
sum up conversion step in first two bypass rxns
pyruate –> oxaloacetate (in mitochondria) –> malate (shuttled out of mitochondria) –> oxaloacetate
why do we need to do a bunch of conversion reactions
becuase there is no oxaloacetate transporter, so it can’t be shuttled out of mitochondria
what enzyme carries out this interconversion
malate dehydrogenase
sum up what malate dehydrogenase does
oxaloacetate –> malate (by malate dehydrogenase), malate shuttled out of mitochondria into cytosol, then cytosolic malate dehydrogenase which does malate –> oxaloacetate
what enzyme does oxaloacetate –> malate
malate dehydrogenase
what enzyme does malate –> oxaloacetate
cytosolic malate dehydrogenase
what happens once we get malate –> oxaloacetate
we can continue on w/ gluconeogenesis
what is 3rd bypass rxn
fructose -1,6-bisphosphate –> fructose-6-phosphate
what enzyme for 3rd bypass rxn
fructose-1,6-bisphosphatase
what kinda rxn (thermodynamically) is fructose-1,6-bisphosphatase
metabolically irreversible rxn
what are allosteric inhibitors of F-1,6-BPase
AMP, fructose-2,6-bisphosphate
what is the glycolytic counterpart for this 3rd bypass rxn
conversion of F6P into F,1-6-BP