Chapter 12: Glucose Metabolism Flashcards
what is the ultimate goal of glycolysis?
To convert a 6 carbon glucose into two 3 carbon pyruvate molecules
is glycolysis anabolic or catabolic?
catabolic
glucose gets broken down
what is gluconeogenesis the reverse rxn for?
glycolysis
pyruvates are converted back to glucose
is glucose the only sugar that can undergo glycolysis?
no.
what happens to the pyruvate that gets produced by glycolysis?
gets broken down to acetyl CoA for use in the citric acid cycle
what ultimately happens to the carbons in a sugar that has been catabolized by glycolysis?
they are ultimately converted to CO2 that help produce electron carriers in the citric acid cycle (NADH and QH2)
What is QH2 the abbreviation for?
ubiquinol
what are the names of the two electron carriers that come out of the citric acid cycle and go in to the electron transport chain?
NADH and QH2
what do electron carriers (NADH and QH2) do in the electron transport chain?
establish a PROTON gradient across the mitochondrial membrane
what does the electron transport chain ultimately achieve?
significant ATP production via oxidative phosphorylation
what is acetyl CoA used for?
power the TCA (Krebs, citric acid) cycle
build up of fatty acid
CANNOT be used to make net glucose molecules
what is glycolysis?
the breakdown of glucose by enzymes, releasing energy and pyruvic acid.
How many ATP, pyruvate, and NADH molecules do you get for each glucose molecules that enters the glycolysis?
2 (net!) ATP (4 total)
2 pyruvates
2 NADH
what are the ‘recipe ingredients’ for the glycolysis pathway?
1 glucose
2 NAD+
2 ATP
2 (inorganic) phosphates
what are the products for the glycolysis pathway?
2 ATP
2 pyruvates
2 NADH
which molecule is bigger: glucose or pyruvate?
glucose
pyruvate is like two halves of a glucose
How many of the 10 steps in glycolysis are enzymatically catalyzed?
all ten of them
which 5 steps in glycolysis are the ‘energy investment’ phase?
the former 5 steps
all 5 of these steps must be completed in order to break even on the 2 ATP investment that was made
which 5 steps in glycolysis are the ‘energy payoff’ phase?
the latter 5 steps
this is where you start using high energy intermediates to begin MAKING ATP
When can the NADH (generated during glycolysis) NOT go on to be used for making additional ATP in the electron transport chain?
can’t be used under ANaerobic conditions
what does Dr. Shimko mean when he says that metabolism occurs by ‘compartmentalization’
certain activities occur within certain parts of the cell:
in keeping with ‘compartmentalization’, where does glycolysis occur within the cell?
the cytosol
in keeping with ‘compartmentalization’, where does gluconeogenesis occur within the cell?
the cytosol
what does it mean to say that a process is ‘cytosolic’?
it means the process occurs within the cell cytosol
Do you need to memorize all the structures in the metabolism chapters
yes 😵💫🤕
what do ‘kinase’ enzymes do?
phosphorylate (add phosphate to) things
what do ‘kinase’ enzymes usually use as their phosphate source?
ATP
what does hexokinase do in glycolysis?
uses ATP to add a phosphate (phosphorylate) glucose
which 3 steps in the glycolysis are IRreversible?
step 1: hexokinase uses ATP to phosphorylate sugar
step 3: Phosphofructo-kinase 1 uses ATP to phosphorylate the original sugar’s isomer
step 10: pyruvate kinase phosphorylate
which steps are most tightly regulated in the glycolysis: the reversible steps or the IRreversible steps?
IRreversible
How many of the 4 hexokinase isoforms are in the human body?
all 4
types 1-3 are in most of your cells, but type 4 is only found in the liver
what are the two names for the hexokinase isoform that is only found in the liver?
hexokinase 4
aka
glucokinase
why do we care about the glucokinase (hexokinse 4) that is only found in the liver?
this one is the only one that is selective such that it can only phosphorylate glucose
the other types can act on glucose AND fructose
what is a metabolite?
A substance made or used when the body breaks down food, drugs or chemicals, or its own tissue (for example, fat or muscle tissue)
what 2 other processes can glucose-6-phosphate be used for (besides continuing on into the glycolysis)?
pentose phosphate pathway
glycogen synthesis
what does it mean to call a pathway step a ‘committed’ step?
it means the step can only produce one outcome/can only follow one pathway
and/or the resulting product of that step can only be used for one purpose
when a sugar is chopped in two at the end of the glycolysis process, why does it matter that the two pieces are as identical as possible?
the two halves need to be able to interconvert in a single step
when a sugar is chopped in two at the end of the glycolysis process, why does it matter that the two pieces are as identical as possible?
the two halves need to be able to interconvert in a single step
when a sugar is chopped in two at the end of the glycolysis process, why can’t the two pieces be exactly identical?
to make both pieces identical, you’d have to phosphorylate the 1 and 6 carbons on the glucose…
but phosphorylating the C1 carbon would destroy its anomeric property, and it needs to keep its anomeric property because it needs to be able to do mutoratation/achieve its linear state in order to be cleaved in half at the end of glycolysis
why does the cell phosphorylate glucose asap/in the first step of glycolysis?
to prevent the glucose from exiting/escaping the inside of the cell.
phosphorylated glucose can’t leave the cell easily as regular glucose because phosphorylated glucose has a charge (that can scarcely cross the membrane) and bc phosphorylated glucose has no concentration gradient outside the cell
do cell membranes have transporters for phosphorylated glucose?
no. Cell has transporters for regular glucose but not for phosphorylated glucose
are hexokinases allowed to phosphorylate all the glucose willy nilly?
no
hexokinase must be regulated to keep it from hoarding all the glucose in any given cell
when you convert an anomeric phosphorylated glucose to fructose in step 2 of glycolysis, is the fructose anomeric as well?
yes
some of the steps in glycolysis are in equilibrium with one another. Are these equilibria guided by Le Chatlier principles?
Yes
are the enzymes in glycolysis identical to the enzymes in it’s reverse rxn (gluconeogenesis)?
7 of the enzymes are identical, but gluconeogenesis has different enzymes for overcoming the irreversible steps in glycolysis
what is the first ‘committed’ step in glycolysis?
step 3: Phosphofructo-kinase 1 uses ATP to phosphorylate the original sugar’s isomer
which committed step in glycolysis is considered THE committed step in glycolysis?
the first ‘committed’
why aren’t all cells able to engage in gluconeogenesis?
running glycolysis and glyconeogenesis ‘is a waste of ATP’
alternative pathways occur instead
Between which two carbons is the glycolysis sugar cleaved?
Between C3 and C4
This cuts the 6 carbon sugar right down the middle
At which glycolysis step is the 6 carbon sugar cleaved into two pieces?
Step 4: cleavage with aldolase
Which carbons from the cleaved 6 carbon sugar becomes dihydoxyacetone phosphate in step 4 of glycolysis?
Carbons 1-3
Which carbons from the cleaved 6 carbon sugar becomes Glyceraldehyde-3-phosphate in step 4 of glycolysis?
Carbons 4-6
do you still need to know the rxn rate enhancement types from the last exam?
YES!!!!
what 2 rate enhancement types does the aldolase enzyme use in step 4 of glycolysis?
covalent catalysis
base catalysis
during glycolysis, when the 6 carbon sugar is cleaved into two trios sugars, which of the two halves is more abundant and lower in engergy: dihydroxyacetone phosphate or glyceraldehyde 3-phosphate?
dihydroxyacetone phosphate is more abundant BECAUSE it is lower in energy
but it is readily isomerized into glyceraldehyde 3-phosphate as needed
in glycolysis, why is the enzyme triose phosphate isomerase so important?
it interconverts the two triose sugars (dihydroxyacetone phosphate or glyceraldehyde 3-phosphate) so that they can both be used in a single/commong pathway rather than needing their own separate pathways.
why does it matter that the triose phosphate isomerase is “perfect”?
being ‘perfect’ (having a rate determining step based on substrate diffusion rather than based on the chemistry step) means that the enzyme can readily keep pace with the demand for glyderaldehyde 3-phosphate
what do kinase enzymes (usually) do?
phosphorylate things
what do dehydrogenase enzymes (usually) do?
redox rxns
what do isomerase enzymes (usually) do?
interconvert isomers
which two steps in glycolysis have complicated ass mechanisms?
step 5 (cleavage of 6 carbon sugar to two 3 carbon sugars)
step 6 (oxidation and phosphorylation of sugar, reduction of NAD+)
how is it that in glycolysis’ step 5, the sugar is both oxidized AND phosphorylated?
the structure that gets attached to the sugar’s carbonyl carbon has an O-P-O structure, to the sugar gains a phosphate group and a bond to an O all at the same time
in which step of glycolysis does the cell break even (with regard to ATP investment)?
step 6
what is substrate level phosphorylation?
when you take a phosphate group from a high energy substrate and give it to ADP in order to make ATP
which step of glycolysis involves substrate level phosphorylation?
step 7
that step where Shimko was even more convoluted than usual. I think he’s smoking crack now.
In step 8 of glycolysis (phosphoglycerate Mutase Rxn) why is it necessary to increase the energy of the 3-phosphoglycerate?
making ATP is not favorable (breaking it is).
In order to make ATP from ADP or AMP, you need to take P from a substrate whose hydrolysis energy is high enough to offset the unfavorability of making ATP
In step 8 of glycolysis, how does the phosphoglycerate Mutase enzyme increase the energy of the sugar ( 3-phosphoglycerate)?
by moving the 3-phosphoglycerate sugar’s phosphate from C3 to C2
How does moving the 3-phosphoglycerate’s phosphate from C3 to C2 increase its energy in step 8 of glycolysis?
moving the sugar’s negatively charged phosphate closer to the sugar’s negatively charged carboxylate functional group causes electron repulsion that raises the energy of the structure.
as glycolysis progresses and sugar is being reacted upon, does the sugar increase in energy or decrease in energy?
increase. Each step brings its energy closer and closer to being able to be used to do substrate level phosphorylation
what enzyme adds phosphate to glucose in step 1 of glycolysis?
hexokinase
what enzyme converts glucose to fructose in step e of glycolysis?
Phosphoglucose isomerase
what enzyme adds phosphate to fructose-6-phosphate in step 3 of glycolysis?
Phosphofructokinase (PFK 1)
what enzyme cleaves fructose-1,6-bisphosphate in step 4 of glycolysis?
Aldolase
what enzyme interconverts dihydroxyacetone phosphate and glyceraldehyde-3-phosphate in step 5 of glycolysis?
Triose phosphate isomerase
what enzyme oxidizes and phosphorilzes glyceraldehyde-3-phosphate in one felt swoop in step 6 of glycolysis?
Glyceraldehyde-3-phosphase dehydrogenase
what enzyme takes a phosphate from 1,3-bisphosphoglycerate and gives it to ADP in step 7 of glycolysis?
Phosphoglycerate kinase
what enzyme moves phosphate from C3 to C2 in 3-phosphoglycerate in step 8 of glycolysis?
phosphoglyceromutase
what enzyme converts 2-phosphoglycerate into its high energy enol isomer during step 9 of glycolysis?
enolase
what enzyme takes phosphate away from phosphoenolpyruvate and gives it to ADP in step 10 of glycolysis?
pyruvate kinase
generally speaking, what are 4 types of reaction inhibition?
product inhibition
feed forward activation
covalent modification
synthesis/degradation
what is feed forward activation?
When an early product in a metabolic pathway allosterically activates an enzyme further downstream
Likely to occur if the system is running low on final product and an upstream product can speed up a slow,, downstream enzyme to speed up product production
what does ‘covalent modification’ describe?
what happens when you reversibly modify an enzyme (after the enzyme has been assembled in the cell) by covalently adding special groups to specific locations
does a metabolic product have to be close to an enzyme in order to inhibit it via product inhibition?
No. Often the product and the enzyme it inhibits are several steps apart (this saves energy)
does ‘covalent modification’ turn metabolic pathways on or off??
it can do either, depending on the situation
what are the two examples of ‘covalent modification’ that we discuss in our class?
phosphorylation by kinases
dephosphorylation by phosphatases
what kind of inhibition inhibits hexokinase in glycolysis?
product inhibition (glucose-6-phosphate)
what kind of inhibition inhibits hexokinase in glycolysis?
product inhibition ??? (glucose-6-phosphate)
why are ADP levels a better indicator of cell energy/sated state than ATP levels?
The range of critical values is wider and fluctuates more often (allowing a more precise monitoring of how sated the cell is)
what enzyme regulates Phosphofructokinase-1?
it’s arch nemesis, Phosphofructokinase-2 (which converts fructose-6-phosphate into Fructose-2,6-phosphate instead of Fructose-1,6-phosphate)
where in the body can you find cells capable of both glycolysis AND gluconeogenesis?
liver and (less so) kidneys
which metabolic pathway is favored when the cellular concentration of fructose-2,6-bisphosphate is HIGH: glycolysis or gluconeogenesis?
glycolysis
