glycolysis Flashcards
What kind of metabolic process is glycolysis?
a catabolic process that converts 1 molecule of glucose into 2 pyruvate molecules
what are the 2 major products from glycolysis?
ATP and NADH
what kind of metabolic process is glycogen synthesis?
an anabolic process
-glycogenolysis
what happens to glucose that is not converted to pyruvate?
it is stored as glycogen
what is gluconeogenesis?
an anabolic process that converts pyruvate to glucose
is glycolysis an aerobic or anaerobic process?
it can occur in both conditions
how many reactions are there in glycolysis?
10 enzyme catalyzed rxn’s
where does glycolysis occur?
in the cytosol
what are the 2 stages of glycolysis?
energy investment
-glucose needs to be acitvated
-ATP consumed
-involves 6C sugars
energy payout
-enegry harvested from ATP
-NADH generated
-involves 3C sugars
what kinds of steps are regulated?
irriversible reactions
what enzyme catalyzes the first step of glycolysis? what does it do?
hexokinase
-converts glucose into glucose 6-phosphate (adds a phosphate group)
what enzyme catalyzes the third step of glycolysis? what does it do?
phosphokinase-1 (PFK-1)
-converts fructose 6-phosphate into fructose 1,6-bisphosphate (addition of another phosphate group)
what enzyme catalyzes the 6th step of glycolysis? what does it do?
glyceraldehyde 3-phosphate dehydrogenase (G3P dehydrogenase)
-converts glyceraldehye 3-phosphate into 1,3-biphosphoglycerate (addition of phosphate)
what enzyme catalyzes the 10th step of glycolysis? what does it do?
pyruvate kinase
-converts phosphoenolpyruvate (PEP) into pyruvate
what is made after the energy investment stage of glycolysis? how many ATP are used?
glucose –> GAP (x2)
-2 ATP are needed per glucose molecule
is the rxn catalyzed by hexokinase regulated? coupled? reversible? what kind of reaction is it?
step 1 in glycolysis
-irreversible
-regulated
-coupled (ATP used)
-high energy molecule consumed
-phosphate transfer rxn
in step 2 of glycolysis what occurs?
a reversible isomerization reaction of glucose
6-phosphate to fructose
6-phosphate
-not coupled
-not regulated
-adehyde to ketone
is the rxn catalyzed by PFK-1 regulated? coupled? reversible? what kind of reaction is it?
-regulated (rate limiting**)
-irreversible
-coupled (ATP) used
-phosphate transfer rxn
what is the rate limiting step in glycolysis?
step 3; conversion of F6P to
F-1,6BP
-regulated by PFK-1
what occurs in the 4th step of glycolysis?
A reversible lysis reaction that converts Fructose 1,6-BP to DHAP and GAP
-not regulated
-not coupled
-lysis rxn
what occurs after the 4th step (lysis) in glycolysis?
DHAP must be converted into GAP in order to form 2 GAP molecules
-reversible
-isomerization
-not regulated
-not coupled
what is the overall reaction in the energy payout stage? how maby ATP are made?
2 GAP –> 2 pyruvate
4 ATP are made for every glucose molecule
What kind of reaction occurs in step 6 of glycolysis?
a reversible oxidation reaction that converts GAP to 1,3-BPG
-catalyzed by GAPDH
- energy capture step
-produces NADH
-phosphate addition NOT transfer
-1,3-BPG is a high energy intermediate
what makes 1,3-BPG a high energy intermediate?
it has a large phosphate transfer potential
what occurs in the 7th step of glycolysis?
ATP is made from 1,3-BPG
-reversible
-energy capture step
- coupled to a substrate level phosphorylation
-phosphate transfer
-1 ATP per 1,3-BPG –> 2ATP total
what occurs in the 8th step glycolysis?
a reversible isomerization
of 3-phosphoglycerate to 2-phosphoglycerate
what occurs in the 9th step of glycolysis?
PEP is generated through a dehydration reaction (H2O removed)
-reversible
-PEP is a high energy intermediate
what occurs in the last step of glycolysis?
pyruvate is made by a substrate-level phosphorylation (phosphate transfer) reaction
-irreversible
-coupled (ATP synthesis)
-energy capture step
-catalyzed by pyruvate kinase
-2 ATP made per glucose
in the final step of glycolysis, what is the high energy intermediate created? how is it converted into pyruvate?
enolpyruvate is a high energy intermediate that spontaneously rearranges to form pyruvate
what is the overall reaction for the investment phase of glycolysis? what is made and what is used?
made: 2 GAP , 2 ADP , 2H+
used: 1 glucose, 2ATP
what is the net production of ATP from glycolysis? in what stage is ATP made/consumed?
2 ATP total
2 used in phase 1
4 made in phase 2
which reactions are considered “energy capture” steps?
step 6 (NADH) , 7 (ATP) and 10 (ATP)
what is an “energy capture step”?
a step that creates a high energy intermediate to be used in the next rxn’s
-6,7,10
which reactions in glycolysis use ATP?
1 and 3
which reactions in glycolysis make ATP?
7 and 10
which reactions in glycolysis make high energy intermediates?
6 and 9
1,3-BPG and PEP
which reaction is the oxidation step? what catalyzes it?
step 6
-conversion of GAP into 1,3-BPG catalyzed by GAP-DH
which reactions in glycolysis are coupled?
1 (ATP used) , 3 (ATP used) , 7 (ATP made), 10 (ATP made)
which reactions are irreversible (regulated) ?
1, 3 and 10
why is glycolysis regulated?
to ensure that energy needs are met and that glucose is not wasted
what 4 processes regulate the rate of flux in metabolic pathways?
1) substrate concentration
-glucise import
2) alterations of enzyme activity
3) alteration of the amount of enzyme
4) compartmentation
what is compartmentation?
regulation at the level of transporters
-increase/decreasing number of transporters
what are the quick regulators for the flux of metabolic pathways?
-substrate availibilty
-alteration of enzyme activity
what 3 enzymes regulate processes in glycolysis?
hexokinase
PFK-1
pyruvate kinase
what are inhibitors of PFK-1?
ATP, citrate and PEP
what are activators of PFK-1?
AMP and Fructose 2,6-BP
what is an inhibitor of pyruvate kinase?
ATP
how is hexokinase regulated?
through product inhibition of Glucose 6-phosphate
what is special about glucose 6-phosphate (G6P)?
it can be used as a pre-cursor to make glycogen
how does AMP/ADP regulate PFK-1 levels?
When cellular energy levels are low, ADP and AMP concentrations increase due to ATP hydrolysis. ADP and AMP bind to allosteric sites on PFK-1, causing a conformational change that increases the enzyme’s affinity for its substrate, fructose-6-phosphate (F6P), and enhances its catalytic activity.
how does PEP regulate PFK-1 levels?
increased levels of PEP will cause a negative feedback resulting in decreased release of PFK-1
how does ATP regulate PFK-1 levels?
ATP serves as an allosteric inhibitor of PFK-1. When cellular energy levels are high and ATP concentrations increase, ATP binds to an allosteric site on PFK-1, causing a conformational change that reduces the enzyme’s affinity for F6P and decreases its catalytic activity.
what does high levels of PEP indicate in glycolysis?
signal that the products of glycolysis are not being consumed
what line would correspond to increased PEP?
the line on the far right
-PEP is a heteroallosteric inhibitor so it would shift to the right indicating a decreased affinity
what line would correspond to increased [AMP]?
the line on the far left
AMP is a positive heteroallosteric activator so it will cause a shift to the left, indicating an increase in activation
how is pyruvate kinase regulated?
allosteric regulation
-inhibited by ATP (product inhibition)
-activated by Fructose 1,6-BP (feed forwrad activation)
what other pathways is the regulation of pyruvate essential to?
glycolysis and gluconeogenesis
Pyruvate activates glycolysis by signaling sufficient substrate availability. It inhibits gluconeogenesis to prevent excessive glucose production, maintaining metabolic balance between glucose breakdown and synthesis.
what effect does F-1,6 BP have on pyruvate kinase?
it will activate pyruvate kinase
-heteroallosteric activator
-feed forward activation
what affect would increased [ATP] have on this graph?
it will shift the graph to the right
-ATP acts as an inhibitor
what must occur in order to maintain
“steady state” ?
reversible reactions help maintain a steady state
-coordination of PFK-1 and PK must be maintained (if one is active the other must be as well)
how many isomerization reactions are there in glycolysis? when do they occur?
3
-step 2, 5 and 8
when does the lysis reaction occur in glycolysis?
step 4
-lysis of F-1,6BP to create GAP and DHAP
in what step does a dehydration reaction occur in glycolysis?
step 9
-dehydratoin to obtain PEP
what is the pre-cursor of glycogen?
glucose 6-phosphate (G6P)
how are the glycosidic bonds in glycogen broken?
inorganic phosphate is used to break glycosidic bonds
Glycogen (N units) + Pi → Glycogen (N-1 units) + Glucose-1-phosphate Glucose-1-phosphate ⇌ Glucose-6-phosphate
how much ATP is needed to generate G6P from glycogen
none
what is the net generation of ATP from the metabolism of glycogen?
3 ATP are made as opposed to 2 in phase 1
-increased net yield of 1 ATP
what anaerobic reactions can pyruvate take part in? what are the products?
pryuvate reduction to form:
ethanol (yeast)
lactate formation in muscle cells
what aerobic reaction can pyruvate take part in? what does this form?
oxidative phosphorylation
-Acetyl coA
why is anaerobic processes involving pyruvate required?
it allows for NAD+ to be regenerate in order to be used in glycolysis under anaerobic conditions
how many pyruvate, NADH and ATP does glycolysis produce?
2 of each
what enzyme converts pyruvate to L-Lactate?
Lactate dehydrogenase (LDH)
what kind of product is lactate?
a “dead-end” product
-not an acid
what kind of reaction occurs from the production of lactate from pyruvate?
a reduction reaction
how is lactate exported from the muscle to the blood?
a specific membrane transporter protein
what happens to the pH of the blood when lactate is produced?
the pH in the bloodstream is lowered as a result of the movement H+ with the movememt of lactate
how does the lowered pH in the blood affect O2 binding to hemoglobin?
affinity for Hb will decrease as a result of the lowered pH (bohr effect)
how does the pH of the muscle cells change as a reuslt of lactate production?
pH increases as H+ and lactate leave the muscles
how is lactate metabolic fuel for cardiac tissue?
In cardiac tissue, lactate serves as a metabolic fuel during periods of increased energy demand or when glucose availability is limited. Lactate can be converted to acetyl-CoA, which enters the citric acid cycle to generate ATP through oxidative phosphorylation
what 2 steps are involved in the anaerobic process of pyruvate to make ethanol? how does this differ from the production of lactate?
decarboxylation and reduction
-there is an additional step of decarboxylation involved in the production of ethanol
what are the final products of anaerobic ethanol production?
ethanol, NAD+ and CO2
what reactions does the pyruvate dehydrogenase reaction link?
links glycloysis with the citric acid cycle
where does the pyruvate dehydrogenase rxn occur?
the mitochondril matrix
what catalyzes the pyruvate dehydrogenase rxn?
pyruvate dehydrogenase complex
-PDC / PDH
why do aerobic processes occur in the mitochondrial matrix?
so that they are connected to the ETC for oxidation
where does glycolysis generate pyruvate?
in the cytosol
what transporter is needed to transport pyruvate across the inner mitochondrial membrane? what is it transported with?
pyruvate translocase
-proton transported with pyruvate
where is pyruvate converted into acetyl coA?
the mitochondrial matrix
is acetyl-coA a high energy molecule? why or why not?
yes
-it has a thioester bond; a high energy bond
how is the acetyl group attached in acetyl coA?
it is attached via a thioester bond
what is the derivative of CoA?
vitamin B5
is the formation of acetyl coA reversible or irreversible?
it is a key irreversible step in carbohydrate metabolism
true or false: you can make glucose from fat but you cannot make fat from glucose
FALSE
-other way around; you can make fat from glucose but not glucose from fat
what are the productse from the pyruvate dehydrogenase rxn?
Acetyl-coA, NADH and CO2
what cofactors are needed for the pyruvate dehydrogenase rxn?
-NAD+
-FAD
-CoA
what is the pyruvate dehydrogenase complex? what is it regulated by?
a multienzyme complex respomnsible for catalyzing the rxn
-regulated by kinases and phosphatases
what 3 compounds regulated PDH ?
NADH (inhibitor)
-allostery
-protein kinase activation
Acetyl-coA (inhibitor)
-protein kinase activation
Ca+ (activator)
-protein phosphatase activation
-dephosphorylation of PDH
what deactivates PDH?
phosphorylation of PDH by a kinase
What activates PDH? What enzyme does this?
dephosphorylation of PDH by phosphotase
does NADH inhibit or activate PDH?
inhibit
does AcetylcoA inhibit or activate PDH?
inhibit
does Ca+ inhibit or activate PDH?
activate
is the phosphorylation that regulates PDH reversible or irreversible?
it is tightly regulated by reversible phosphorylation
is the pyruvate dehydrogenase complex inhibited by substrate or product availability?
inhibited by the products
-NADH and Acetyl-coA
how is the pyruvate dehydrogenase complex activated by substrate availability?
activation by the substrates
-NAD+ and HS-CoA
