Module 2 Glycolysis

Question 1

where does glycolysis occur

Answer 1

in the cytosol

Question 2

Glycolysis

Answer 2

the sequence of reactions that converts one molecule of 6 carbon molecule glucose to two molecules of three carbon molecule pyruvate

Question 3

what are the two major functions of glycolysis

Answer 3

1. Generates ATP
2. a number of intermediates of this pathway serve as building blocks for the biosynthesis of other biomolecules such as amino acids and fatty acids

Question 4

how much atp is created and consumed in glycolysis

Answer 4

two ATP consumed in the first stage of the pathway, but 4 ATP produced in the second stage (2 ATP produced per 3 carbon molecule)

Question 5

what is the net ATP produced

Answer 5

2 ATP per molecule of glucose

Question 6

how does glucose enter the cell

Answer 6

NOT through diffusion through the membrane.

it needs GLUT (GLUT 1-5) transporters (specific protein transporters)

Question 7

energy consumption phase

Answer 7

steps 1-5

Question 8

energy producing phase

Answer 8

steps 5-10

Question 9

what are the steps of glycolysis

Answer 9

1. phosphorylation of glucose
2. Glucose-6-P converted to Fructose-6-P
3. Fructose-6-P is phosphorylated
4. Cleavage of fructose 1,6 Bisphosphate to GAP and DHAP
5. oxidation GAP to 1,3-BPG
6. phosphoryl transfer from 1,3 BPG to 3 PG
7. Step 7: 3-phosphoglycerate kinase is converted to 2-phosphoglycerate by phosphoglycerate mutase

Question 10

step 1 phosphorylation of glucose

Answer 10

phosphorylation of glucose

glucose enters the cell and is rapidly phosphorylated by hexokinase (while using ATP) to form glucose-6-phosphate and consumes 1 ATP

Question 11

step 2

Answer 11

Glucose-6-P is converted to Fructose-6-P

an isomerization reaction (no atoms lost or added, just a rearrangement

done by phosphoglucose isomerase. the reaction is necessary because glucose-6-p is not readily cleaved into 3-carbon fragments, but fructose-6-P is

Question 12

Step 3

Answer 12

Step 3: Fructose-6-P is phosphorylated at a second carbon to form fructose-1,6-bisphosphate

irreversible reaction

catalyzed by phosphofructokinase, which is regulated allosterically.

IMPORTANT REGULATORY STEP

CONSUMES A SECOND ATP

Question 13

Step 4

Answer 13

Step 4: Cleavage of fructose 1,6-bisphosphate to two different 3-carbon molecules

(DHAP and GAP)

GAP is the molecule that proceeds directly onward in the pathway. DHAP can be converted to GAP by an isomerase

Question 14

Step 5

Answer 14

Step 5: Oxidation of glyceraldehyde-3-P powers the formation of 1,3-bisphosphogycerate which has high phosphoryl-transfer activity.

uses a dehydrogenase, which is an enzyme that catalyzes redox reactions and utilizes electron acceptors such as NAD+ and FAD

a phosphate group is attached to a carboxylic acid group, and this has high phosphoryl transfer potential, which will allow for the synthesis of ATP in the next step

Question 15

Step 6

Answer 15

Step 6: Phosphoryl transfer from 1,3-bisphosphoglycerate to ADP to form ATP

the first energy producing step in glycolysis

catalyzed by phosphoglycerate kinase

ate formed here is called substrate level phosphorylation

produces 3 phosphoglycerate and ATP

two ATP formed at this step with every glucose started with

Question 16

step 7

Answer 16

Step 7: 3-phosphoglycerate kinase is converted to 2-phosphoglycerate by phosphoglycerate mutase

mutates are isomerases that reposition phosphate groups within a molecule

ATP is formed when phosphenolpyruvate is converted to pyruvate by pyruvate kinase

Question 17

what is the overall free energy change in glycolysis

Answer 17

-22 kcal/mol

Question 18

does glycolysis flow in both ways

Answer 18

no, it flows towards the production of pyruvate

Question 19

what is the pathway from glucose to pyruvate called

Answer 19

anaerobic glycolysis

Question 20

why does glycolysis not come to a halt

Answer 20

because of the replenishing of NAD+ achieved through the metabolism of pyruvate

Question 21

what are the three possible fates of pyruvate

Answer 21

1. acetaldehyde then ethanol: occurs in yeast. consists of decarboxylation (loss of CO2) reaction to form acetaldehyde and a redox reaction whereby acetaldehyde becomes reduced to ethanol from electrons donated by NADH
2. Lactate: NADH is used to reduce pyruvate to lactate, and in the process regenerating NAD+. Thus, the conversion of glucose to lactate is also redox neutral

3 acetyl CoA: where most energy is obtained from pyruvate, because acetyl CoA is the entry point into the citric acid cycle. NAD+ is not regenerated in this reaction.

Question 22

Auto-brewery syndrome

Answer 22

people can create ethanol from pyruvate due to fermentation in the gut. this intoxicates them. its due to fermentation in the lack of oxygen. they have an imbalance in their microbiome that is often caused by antibiotics, poor diet, or health conditions. treatment is dietary changes, probiotics, and sometimes medication

Question 23

Lactose intolerance

Answer 23

has trouble metabolizing lactose due to a deficiency in the enzyme lactase found in our small intestine. 75% of the world is lactose intolerant.

Question 24

fructose conversion in liver

Answer 24

fructose is phosphorylated to fructose 1 p by fructokinase, then split into 3 carbon molecules to dihydroxyacetone phosphate and glyceraldehyde by a special aldolase. this pathway bypasses phosphofructokinase which is the key regulatory step in glycolysis, leading to uncontrolled metabolic flux. as a result, excess pyruvate is formed and converted to acetylene co a which is a precursor for fatty acid synthesis. these fatty acids are stored in adipose tissue and may accumulate in the liver.

Question 25

what are the regulated enzymes in glycolysis

Answer 25

hexokinase, phosphofructokinase, and pyruvate kinase

Question 26

what are the two main roles of glycolysis

Answer 26

-break down glucose and produce ATP -provide building blocks for biosynthesis

Question 27

where does control points in metabolism occur

Answer 27

at irreversible steps

Question 28

what are the three control points in glycolysis

Answer 28

1. hexokinase 2. phosphofructokinase 3. pyruvate kinase these are all regulated by allosteric effectors and covalent modification

Question 29

glycolysis in muscle

Answer 29

provides ATP that is used for muscle contraction and is primarily controlled by the energy state of the cell, which is represented by the ATP:AMP ratio High ATP - glycolysis slows down High AMP - glycolysis speeds up

Question 30

key regulatory enzymes in muscle

Answer 30

PFK is the most important control point. it is controlled allosterically. decreases affinity for substrate fructose-6-P. AMP competes for the same site. when it's bound it does not inhibit the enzyme. this is how the ratio of ATP: AMP controls the rate of glycolysis hexokinase is also an allosteric mechanism. glucose-6-P levels are watched. it slows the first step of glycolysis which will cause glucose to build up in muscle and slow the uptake of glucose from the blood into the muscle pyruvate kinase in allosterically inhibited by ATP and activated by fructose 1,6-bisP. this metabolite is an intermediate in glycolysis, and the product of PFK, which is the major rate limiting enzyme. a rise in fructose 1-6 bisP is a clear indication of increased influx through the pathway, so pyruvate kinase activity is increased to handle the increased flux that is headed in its direction

Question 31

glycolysis in liver

Answer 31

does not rely on glycolysis for ATP. helps regulate blood glucose. glucose is taken up as: stored as glycogen used to generate reducing power in the form of NADPH which is used for biosynthesis converted via glycolysis to molecules that serve as building blocks for synthesis of other biomolecules

Question 32

key regulatory signals in the liver

Answer 32

1. Phosphofructokinase (PFK) is inhibited by citrate since it is formed from acetyl CoA which in turn is a product of pyruvate metabolism. A high level of citrate is an indicator that biosynthetic precursors are at sufficient levels, and metabolizing more glucose through glycolysis can be slowed. 2. Glycolysis in the liver responds to high blood sugar in a unique way. When glucose rises in the blood after a meal, the liver takes up much of this. There is more flux through glycolysis which leads to build up of fructose-6-P levels, so the enzyme PFK is activated to handle the increase in this metabolite. 3. To achieve this, some of the fructose-6-P is converted to fructose-2,6-P. Fructose-2,6-bisP is an allosteric activator of PFK, which it does by increasing its affinity for one of its substrates and by blunting the inhibitory effect of ATP Fructose-2,6-bisP is NOT part of glycolysis itself, but acts as a powerful signal and will be discussed in a future module.

Question 33

how is hexoinase regulated in the liver

Answer 33

The liver has a unique form of hexokinase called glucokinase Glucokinase in the liver is unique from that in muscle in two ways: Much higher Km (lower affinity) for glucose, so it becomes relevant only when glucose is abundant Not inhibited by glucose-6-phosphate, allowing continued uptake, phosphorylation, and storage of excess glucose after meals This setup ensures that liver only takes in and stores glucose after other tissues (like brain and muscle) have had their share.