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Muscles work better when?
when O2 is aroud
What are the pathways glucose can go through?
(fermentation)--> ethanol or lactate
(O2)--> Complete oxidation
Why does it covert?
monosaccharide; six carbon aldose
We want the carbon exposed because its a potential site for phosphorylation; we need two sites though, so we have to convert it to a ketone
Fructose has __.
Lots of __ to be removed and use as __.
Any enzyme working on it only works on an __.
two potential phosphorylation sites
open ring form (has to open it up)
binding site of one side of cell opens to other side of cell
glucose transport protein
Explain the family of glucose transporters.
members of family of proteins that have structure in common
12 transmembrane segments
all single polypeptide chains (500 amino acids long)
binding sites for glucose in extracellular domain, always on outside
Glucose transport proteins arrangement in the membrane?
don't stretch out; form a more complex unit; undergo eversion to get glucose out of cell
What do the different forms of glucose transport proteins affect?
affinity for glucose
enables cells that really need energy in times of distress to get it
What would a low Km and high Km indicate for the glucose transporters?
low Km: binds glucose at low concentration: high affinity
high Km: binds at high concentration
Once glucose is in the cell, what happens?
it can go through a pathway
Stages of the glycolytic pathway.
stage one: investment and cleavage--> 6 carbon glucose--> 2 3 carbon phosphorylated molecules
2 ATP are lost
Stage 2: net gain phase
If glucose gets out, what happens?
you can't get energy from it. Keep it in by changing characteristics
1st step of glycolysis results in __.
one molecule of ATP lost
Why is hexokinase unique?
not active until substrates are bound; induced fit model of activity; suggests a conformational change
Inactive form of hexokinase?
hexokinase has a hinge open. You don't want ATP in active site, hydrolyzed for no reason.
Closes when glucose binds, changes conformation, hinge closes, and 2 lobes come closer; a hydrophobic pocket forms--> ATP binds--> hydrolysis
What is wrong with glucose 6-phosphate an what has to change?
- there is no substrate in ring form.
- So, its opened up. Yet, in its open chain form, it is an alehyde, which isn't useful because we want a free carbon.
It is converted to fructose 6-phosphate, which is converted to its ring form.
SUMMARY: G6P is converted to F6P by opening it, isomerizing it, and reforming the five carbon ring
Committed step of glycolysis
you can't back up or remake the ATP
ATP is a __.
Changing up the molecule and creating something that __.
has high transfer phosphoryl potential
What is the last step of the first stage of the pathway?
chop it in half to two different reverse aldol condensation
2 3 carbon sugars form--> DHAP (dihydroxyacetone) and GAP (glyceraldehyde 3-phosphate)
last part of stage 1 is conversion of DHAP to GAP
GAP does what?
DHAP does what?
GAP: next substrate in pathway
DHAP: must be converted to GAP
What is the structure of triose phosphate isomerase?
unique structure: antiparallel beta sheets--> barrel/ alpha helices
important amino acid side chains= histidine and glutamic acid
What is important about the loop?
important because a conformational change occurs with that loop of protein
connects beta sheet core to alpha helix (periphery)
What does the enediol intermediate need to be ?
needs to be trapped
What is the main goal of the triose phosphate isomerase?
- transfer electrons from one another
- side chains needed for this
Key: enediol intermediate (unstable) gets phosphorylated
What is the first step of the triose phosphate isomerase reaction?
What is the purpose of the loop?
Stage 1: invested one ATP to get phosphate or--> highly unstable
it closes down like a lid on the active site and locks the enediol intermediate, preventing its release until reaction is complete
Summarize part one?
Invested energy to charge up to part where it has some phosphoryl potential but not able to transfer it yet
What is stage two all about?
generate a molecule with high transfer ph. potential
What does glyceraldehyde 3- phosphate dehydrogenase?
Take inorganic phosphate and add to substrate
How to get the glyceraldehyde 3-phosphate dehyrogenase reaction to happen?
dehydrogenase: enzyme that couples two reactions; the highly unfavorable with the highly favorable
remove electrons and protons with release of free energy
How is energy captured when coupling reactions?
in the thioester intermediate
a phosphate in a covalent bond between enzyme and substrate
What is another cofactor?
In the glyceraldehyde 3- phosphate dehydrogenase reaction, what needs to happen?
What is the key?
remove electrons from teh carbonyl carbon and donate to NAD+. To do this, cysteine acts as a nucleotide, drawing electrons to it and making transfer easier.
cysteine acts as nucleophile
What is the second step in the glyceralehyde-3-phosphate dehydrogenase pathwy?
evidence shows NADH must leave and be replaced by NAD+