Metabolism 3: Glycolysis Flashcards
What is glycolysis?
The sequence of reactions that metabolises glucose to pyruvate with the accompanying production of energy
What are the overall products of glycolysis?
Glycolysis converts glucose into two three carbon units and two molecules of adenosine triphosphate (ATP)
Where is glucose metabolised in humans?
In cytosol in the cytoplasm - enters by a specific transporter
What are the two classifications of monosaccharide?
Aldoses and ketoses
How does glucose interconvert between alpha and beta forms?
By mutorotation
The reversible ring opening of each anomer to the open chain aldehyde form
Why is beta pyranose more common than alpha pyranose?
Because large groups prefer to be as spaced out as possible
In beta pyranose, the -OH groups are in the cis form, and point as far away as possible
What is the most common sugar consumed in our diets?
Sucrose
A disaccharide made up of a 6-membered ring of glucose and a 5-membered ring of fructose
How is sucrose broken down in the body?
Salivary glands in the mouth release salivary amylase which partially hydrolyses sucrose in the mouth
In the stomach, acid further hydrolyses
The majority of sugar digestion occurs in the small intestine catalysed by membrane-bound sucrase
What is the first step of glycolysis?
Phosphorylation of glucose by ATP to give glucose-6-phosphate
Which enzyme catalyses step 1 of glycolysis?
Hexokinase
What are the two parts to step 1 of glycolysis?
Attachment of glucose to hexokinase
Hydrolysis of ATP
Where does equilibrium lie in step 1 of glycolysis?
In favour of the products because the overall free energy is negative
What condition is important for the first part of step 1 of glycolysis, and why?
Glucose must bind to hexokinase in a water-free environment to prevent ATP hydrolysis from occuring at this stage in the reaction
Ensures that glucose acts as the nucleophile
How does glucose act as a nucleophile in step 1 of glycolysis?
Aspartic acid residues in hexokinase act as a base to deprotonate the -OH group on carbon-6 of glucose
Allows O- to act as a nucleophile
Nucleophilic attack occurs on the terminal phosphate of ATP
New covalent bond forms, phosphorylating glucose and forming a molecule of ADP
Which bond breaks to form ADP in step 1 of glycolysis?
The phosphoanhydride bond between beta and gamma phosphates in ATP
What is an amino acid residue?
An amino acid that has been incorporated into a protein with its free amino acids and carboxyl groups replaced by linkages to neighbouring residues
How does glucose bind to hexokinase in step 1 of glycolysis?
Via induced-fit mechanism
What is the role of Mg2+ ions in step 1 of glycolysis?
Mg2+ is a cofactor
Mg2+ binds to ATP to form MgATP - stabilises ATP by reducing electrostatic repulsion by partially neutralising the negative charges on the oxygens in the phosphate groups
What is the second step of glycolysis?
Conversion of glucose-6-phosphate to fructose-6-phosphate
Which enzyme catalyses step 2 of glycolysis?
PhosphoGlucose Isomerase (PGI)
Describe how step 2 of glycolysis occurs.
1) Pyranose ring opens via the breaking of the hemiacetal bond to form an open chain
2) Isomerisation occurs in a mechanism of proton transfer catalysed by acid-base chemistry using active site amino acid residues
3) The carbonyl on carbon-1 of glucose is protonated, converting the aldehyde group into a hydroxy group
4) Hydroxyl group on carbon-2 of glucose is deprotonated, forming an enediol intermediate
5) A proton is then transferred to carbon-2, enabling the rearrangement into the ketose form
6) Hemiketal bond forms, allowing the ring structure of fructose-6-phosphate to form
What are the three amino acid residues involved in step 2 of glycolysis?
Glutamic acid (Glu)
Lysine (Lys)
Histidine (His)
What is a hemiacetal bond?
The bond between the -OH group and the aldehyde group in glucose
This bond is why the sugar ring is closed
Breaking this ring leads to formation of the open-chain form of the molecule
What is a hemiketal bond?
The bond between the -OH group and the ketone group in glucose
This bond must be formed at the end of step 2 of glycolysis to form a closed ring ketose structure
Is there a cofactor involved in step 2 of glycolysis?
No
Active site residues on the surface of PhosphoGlucose Isomerase catalyse the reaction
What is the third step of glycolysis?
The phosphorylation of fructose-6-phosphate to form fructose-1,6-bisphosphate
Which enzyme catalyses step 3 of glycolysis?
Phosphofructokinase (PFK)