Glycolysis I Flashcards
(52 cards)
What are the first five metabolic intermediates in glycolysis?
- Glucose
- Glucose-6-phosphate
- Fructose-6-phosphate
- Fructose-1,6-bisphosphate
- Glyceraldehyde-3-phosphate (and diacylglycerol)
What enzyme catalyzes the formation of glucose to glucose-6-phosphate?
Hexokinase
Hexokinase catalyzes what type of reaction?
A phosphorylation
What is the mechanism for hexokinase?
A phosphoryl transfer:
The hydroxyl group of glucose C6 acts as a nucleophile and attacks the gamma phosphate of ATP
What enzyme catalyzes the formation of fructose-6-phosphate from glucose-6-phosphate?
Phosphohexoisomerase
What is the mechanism of phosphohexoisomerase?
An aldo-keto isomerization
Is the first step of glycolysis reversible?
No
Is the second step of glycolysis - the aldoketo isomerization of glucose-6-phosphate to fructose-6-phosphate - reversible? If so, what is the reverse mechanism?
Yes, it is reversible
- General base 1 deprotonates C1 of fructose-6-phosphate; electrons flow to form C1-C2 alkene and hydroxyl group at C2 via deprotonation of general base 2
- The ENEDIOL intermediate is formed
- General base 2 deprotonates hydroxyl group at C1, forming the C1 carbonyl, and protonating the C1-C2 alkene from general base 1 to form glucose-6-phosphate
What is the second step of glycolysis?
The aldo-keto isomerization of glucose-6-phosphate to fructose-6-phosphate via phosphohexoisomerase
What is the third step in glycolysis?
The phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate by phosphofructokinase-1
Is the third step in glycolysis reversible?
No
Like the first step of glycolysis, the third step of glycolysis requires what cofactor?
ATP
What is the mechanism of phosphofructokinase-1?
Phosphoryl transfer:
The C1 hydroxyl of C1 functions as a nucleophile and attacks the gamma phosphate of ATP
Why are the first and third steps of glycolysis irreversible?
Because they are phosphoryl transfers from ATP
What is the fourth step of glycolysis?
The formation of glyceraldehyde-3-phosphate and dihydroxyacetone phosphate via aldolase from fructose-1,6-bisphosphate
What reaction does aldolase catalyze?
The making/breaking of carbon-carbon double bonds:
The formation of glyceraldehyde-3-phosphate and dihydroxylacetone phosphate from fructose-1-6-bisphosphate
What is the mechanism of aldolase?
The making and breaking of C=C bonds:
- The nitrogen of lysine (in active site of aldolase) attacks the carbonyl carbon of fructose-1,6-bisphosphate, forming a hydroxyl group in the process
- A hydrogen atom on the nitrogen of lysine “kicks back” and forms a double bond between the nitrogen and carbon, ultimately releasing water
- The oxygen atom of an aspartate residue (in active site of aldolase) acts as a general base, deprotonating the oxygen of hydroxyl group on C4, causing the bond between C3 and C4 to break and yielding glyceraldehyde-3-phosphat and an ENAMINE intermediate
- The lone pair on nitrogen “kicks back” and causes the alkene between C2 and C3 to deprotonate the aspartic acid residue
- A water molecule deprotonates and forms a hydroxyl group that acts as a nucleophile, attacking the carbon of the enamine
- The hydroxyl group “kicks back,” forming a carbonyl group that then kicks out the lysine residue and forming dihydroxyacetone phosphate
What two amino acid residues are crucial to the functioning of aldolase?
The lysine and aspartate residues
In the fourth step of glycolysis, aldolase contains a lysine residue that functions first as a _________________.
Nucleophile
Aldolase catalyzes a __________________ reaction, meaning that one of its byproducts is a water molecule.
Dehydration
The aspartate residue in aldolase functions first as a _________________ ______________, deprotonating C4 of the intermediate.
General base
Which amino acid residue in aldolase is responsible for triggering the C=C breakage?
Aspartate
The immediate products of aldolase’s cleavage of fructose-1,6-bisphosphate are glyceraldehyde-3-phosphate and an ________________ intermediate.
Enamine
Because an enamine is unstable, the lone pair on nitrogen reforms a double bond with carbon and the alkene deprotonates what amino acid residue in aldolase?
Aspartic acid
