Glycolysis

Question 1

Define Glycolysis

Answer 1

“The sequence of reactions that metabolises one molecule of glucose to two molecules of pyruvate with the net production of two molecules of ATP”

Question 2

What molecules are formed in glycolysis, starting from glucose and ending at pyruvate?

Answer 2

1. Glucose
2. Glucose 6-phosphate
3. Fructose 6-phosphate
4. Fructose 1,6-bisphotphate
5. Glyceraldehyde 3-phosphate (and dihydroxyacetone phosphate)
6. 1,3-Bisphosphoglycerate
7. 3-Phosphoglycerate
8. 2-Phosphoglycerate
9. Phosphoenolpyruvate
10. Pyruvate

Question 3

Fill in the missing molecules:

Answer 3

Question 4

Fill in the missing enzymes:

Answer 4

Question 5

What are the types of reactions that the enyzmes in glycolysis carry out?

Answer 5

1. Phosphoryl transfer
2. Isomerisation
3. Phosphoryl transfer
4. Aldol Cleavage
5. Isomerisation
6. Phosphorylation couples to oxidation
7. Phosphoryl transfer
8. Phosphoryl shift
9. Dehydration
10. Phosphoryl transfer

Question 6

Stage one begins with the conversion of glucose into ________ ___________, which consists of three steps: phosphorylations, isomerisation, and another phosphorylation. It is completed with the cleavage of the ________ ___________ into two three-carbon fragments: _________ __________** and ________________ _________.**

Answer 6

Stage one begins with the conversion of glucose into fructose 1,6-bisphosphate, which consists of three steps: phosphorylations, isomerisation, and another phosphorylation. It is completed with the cleavage of the fructose 1,6-bisphosphate into two three-carbon fragments: **glyceraldehyde 3-phosphate **and dihydroxyacetone phosphate.

Question 7

Glucose enters cells through specific transport proteins and has one principal fate: it is ___________** **by ATP to form ______ __________. This step is notable for two reasons: (1) _______ _________ cannot pass through the membrane because it is not a substrate for the glucose transporters, and (2) the addition of the _________ group acts to destabilize glucose, thus facilitating its further metabolism. The transfer of the _________ group from ATP to the hydroxyl group on carbon __ of glucose is catalyzed by __________.

Answer 7

Glucose enters cells through specific transport proteins and has one principal fate: it is **phosphorylated **by ATP to form glucose 6-phosphate. This step is notable for two reasons: (1) glucose 6-phosphate cannot pass through the membrane because it is not a substrate for the glucose transporters, and (2) the addition of the phosphoryl group acts to destabilize glucose, thus facilitating its further metabolism. The transfer of the phosphoryl group from ATP to the hydroxyl group on carbon 6 of glucose is catalyzed by hexokinase.

Question 8

What is the equation for the formation of **acetyl CoA **from pyruvate?

Answer 8

Pyruvate + NAD⁺ + CoA → acetyl CoA + CO₂ + NADH + H

Question 9

What is the function of a kinase?

Answer 9

Kinases are enzymes that catalyze the transfer of a phosphoryl group from ATP to an acceptor.

Question 10

The isomerization of glucose 6-phosphate to fructose 6-phosphate is a conversion of an ______ into a ______.

Answer 10

The isomerization of glucose 6-phosphate to fructose 6-phosphate is a conversion of an aldose into a ketose.

Question 11

Glyceraldehyde 3-phosphate is on the direct pathway of glycolysis, whereas _____________ ________ is not. Unless a means exists to convert _____________ ________ into glyceraldehyde 3-phosphate, a three carbon
fragment useful for generating ATP will be lost. These compounds are isomers that can be readily interconverted: _____________ ________ is a ketose, whereas glyceraldehyde 3-phosphate is an _____. The isomerization of these three-carbon phosphorylated sugars is catalyzed by ______ _________ __________.

Answer 11

Glyceraldehyde 3-phosphate is on the direct pathway of glycolysis, whereas dihydroxyacetone phosphate is not. Unless a means exists to convert dihydroxyacetone phosphate into glyceraldehyde 3-phosphate, a three carbon fragment useful for generating ATP will be lost. These compounds are isomers that can be readily interconverted: dihydroxyacetone phosphate is a ketose, whereas glyceraldehyde 3-phosphate is an aldose. The isomerization of these three-carbon phosphorylated sugars is catalyzed by triose phosphate isomerase.

Question 12

What is the overall reaction for the conversion of glucose into pyruvate?

Answer 12

Glucose + 2P_i + 2 ADP + 2 NAD⁺→ 2 pyruvate + 2 ATP + 2 NADH + 2 H⁺ + 2 H₂

Question 13

What are the three main products that can be formed from pyruvate?

Answer 13

1. Ethanol
2. Lactate
3. Acetyl CoA

Question 14

_______is formed from pyruvate in a variety of microorganisms in a process called ______ ____** **fermentation. The reaction also takes place in the cells of higher organisms when the amount of oxygen is limiting, as in ______ cells during intense activity. The reduction of pyruvate by NADH to form ______ is catalysed by ______ _____________.

Answer 14

**Lactate **is formed from pyruvate in a variety of microorganisms in a process called **lactic acid **fermentation. The reaction also takes place in the cells of higher organisms when the amount of oxygen is limiting, as in muscle cells during intense activity. The reduction of pyruvate by NADH to form lacate is catalysed by lactate dehydrogenase.

Question 15

What is the purpose of the gluconeogenic pathway?

Answer 15

To convert pyruvate into glucose

Question 16

What are the main noncarbohydrate precursors for gluconeogenesis?

Answer 16

Lactate, amino acids, and glycerol

Question 17

Gluconeogenesis in the _____ and ______ helps to maintain the glucose level in the _____ so that the brain and muscle can extract sufficient glucose from it to meet their metabolic demands.

Answer 17

Gluconeogenesis in the **liver **and **kidney **helps to maintain the glucose level in the **blood **so that the brain and muscle can extract sufficient glucose from it to meet their metabolic demands.

Question 18

In glycolysis the following reaction occurs:

How is this bypassed in gluconeogenesis?

Answer 18

Question 19

In glycolysis the following reaction occurs:

How is this bypassed in gluconeogenesis?

Answer 19

Question 20

In glycolysis the following reaction occurs:

How is this bypassed in gluconeogenesis?

Answer 20

Question 21

In gluconeogenesis, oxaloacetate is transported from a mitochondrion in the form of ______: oxaloacetate is reduced to malate inside the mitochondrion by an NADH-linked ______ ____________.

Answer 21

In gluconeogenesis, oxaloacetate is transported from a mitochondrion in the form of malate: oxaloacetate is reduced to malate inside the mitochondrion by an NADH-linked malate dehydrogenase.

Question 22

To keep glucose inside the cell, the generation of free glucose is controlled in two ways.

1. The enzyme responsible for the conversion of glucose 6-phosphate into glucose, _______-__-___________, is regulated.
2. The enzyme is present only in tissues whose metabolic duty is to maintain _____-_______ homeostasis i.e. the _____ and ______.

Answer 22

To keep glucose inside the cell, the generation of free glucose is controlled in two ways.

1. The enzyme responsible for the conversion of glucose 6-phosphate into glucose, glucose 6-phosphatase, is regulated.
2. The enzyme is present only in tissues whose metabolic duty is to maintain blood-glucose homeostasis i.e. the liver and kidney

Question 23

The glycolytic pathway has a dual role; it degrades ________ to generate ATP and it provides building blocks for synthetic reactions, such as the formation of _____ ______.

Answer 23

The glycolytic pathway has a dual role; it degrades glucose to generate ATP and it provides building blocks for synthetic reactions, such as the formation of fatty acids.

Question 24

Reactions catalysed by what enzymes are virtually irreversible in glycolysis? [3]

Answer 24

Reactions catalysed by:

• Hexokinase
• phosphofructokinase
• pyruvate kinase

Question 25

Phosphofructokinase is the most important control site in the mammalian glycolytic pathway. High levels of ___ allosterically inhibit the enzyme. ___ binds to a specific _________ site that is distinct from the catalytic site. The binding of ___ \_\_\_\_\_\_\_ the enzyme’s affinity for fructose 6-phosphate. Thus, a \_\_\_\_ concentration of ___ converts the hyperbolic binding curve of fructose 6-phosphate into a sigmoidal one. AMP reverses the inhibitory action of \_\_\_, and *so the activity of the enzyme _________ when the ATP/AMP ratio is lowered*. In other words, *glycolysis is _________ as the energy charge falls*. A _______ in pH also inhibits phosphofructokinase activity by augmenting the inhibitory effect of \_\_\_. The pH might fall when muscle is functioning anaerobically, producing excessive quantities of _____ \_\_\_\_. The inhibitory effect protects the muscle from _______ that would result from the accumulation of too much acid.

Answer 25

Phosphofructokinase is the most important control site in the mammalian glycolytic pathway. High levels of **ATP** allosterically inhibit the enzyme. **ATP** binds to a specific **regulatory** site that is distinct from the catalytic site. The binding of **ATP** **lowers** the enzyme’s affinity for fructose 6-phosphate. Thus, a **high** concentration of **ATP** converts the hyperbolic binding curve of fructose 6-phosphate into a sigmoidal one. AMP reverses the inhibitory action of **ATP**, and *so the activity of the enzyme **increases** when the ATP/AMP ratio is lowered*. In other words, *glycolysis is **stimulated** as the energy charge falls*. A **decrease** in pH also inhibits phosphofructokinase activity by augmenting the inhibitory effect of **ATP**. The pH might fall when muscle is functioning anaerobically, producing excessive quantities of **lactic acid**. The inhibitory effect protects the muscle from **damage** that would result from the accumulation of too much acid.

Question 26

Hexokinase, the enzyme catalyzing the _____ step of glycolysis, is inhibited by its product, \_\_\_\_\_\_\_\_-\_\_-\_\_\_\_\_\_\_\_\_. _____ concentrations of this molecule signal that the cell no longer requires _______ for energy or for the synthesis of glycogen, a storage form of \_\_\_\_\_\_\_, and the \_\_\_\_\_\_\_will be left in the blood.

Answer 26

Hexokinase, the enzyme catalyzing the **first** step of glycolysis, is inhibited by its product, **glucose 6-phosphate**. **High** concentrations of this molecule signal that the cell no longer requires **glucose** for energy or for the synthesis of glycogen, a storage form of **glucose**, and the **glucose** will be left in the blood.

Question 27

The inhibition of **phosphofuctokinase** leads to the inhibition of what other enzyme?

Answer 27

Hexokinase

Question 28

Why is **phosphofructokinase** rather than **hexokinase** the pacemaker of glycolysis?

Answer 28

In muscle, **glucose 6-phosphate** can also be converted into glycogen. The first irreversible reaction **unique** to the glycolytic pathway, the **committed step**, is the phosphorylation of fructose 6-phosphate to fructose 1,6-bisphosphate. Thus, it is highly appropriate for **phosphofructokinase** to be the primary control site in glycolysis.

Question 29

Define **allosteric control**

Answer 29

The **regulation** of a protein by binding an effector molecule at a site **other** than the protein's active site. The site the effector binds to is termed the **allosteric site**.

Question 30

Pyruvate kinase, the enzyme catalyzing the _____ irreversible step in glycolysis, controls the _______ from this pathway. This final step yields ATP and \_\_\_\_\_\_\_\_, a central metabolic intermediate that can be ________ further or used as a building block. ATP allosterically ________ pyruvate kinase to slow glycolysis when the energy charge is \_\_\_\_. Finally, alanine also allosterically _______ pyruvate kinase—in this case, to signal that building blocks are abundant. When the pace of glycolysis \_\_\_\_\_\_\_\_\_, fructose 1,6-bisphosphate, the product of the preceding irreversible step in glycolysis, activates the ______ to enable it to keep pace with the oncoming high flux of intermediates.

Answer 30

Pyruvate kinase, the enzyme catalyzing the **third** irreversible step in glycolysis, controls the **outflow** from this pathway. This final step yields ATP and **pyruvate**, a central metabolic intermediate that can be **oxidized** further or used as a building block. ATP allosterically **inhibits** pyruvate kinase to slow glycolysis when the energy charge is **high**. Finally, alanine also allosterically **inhibits** pyruvate kinase—in this case, to signal that building blocks are abundant. When the pace of glycolysis **increases**, fructose 1,6-bisphosphate, the product of the preceding irreversible step in glycolysis, activates the **kinase** to enable it to keep pace with the oncoming high flux of intermediates.

Question 31

The **gluconeogenic pathway **converts pyruvate into what?

Answer 31

Glucose

Question 32

In contracting __________ muscle, the formation and release of _______ lets the muscle generate ATP in the absence of oxygen and shifts the burden of metabolizing _______ from muscle to other organs.

Answer 32

In contracting **skeletal** muscle, the formation and release of **lactate** lets the muscle generate ATP in the absence of oxygen and shifts the burden of metabolizing **lactate** from muscle to other organs.

Question 33

What are the two fates of **lactate **in the blood?

Answer 33

* In one fate, the plasma membranes of some cells contain carriers that make the cells highly permeable to lactate. These molecules diffuse from the blood into such permeable cells. Once inside these cells, lactate can be reverted back to **pyruvate** and **metabolized** through the citric acid cycle and oxidative phosphorylation to **generate ATP.** * In the other fate, excess lactate enters the **liver** and is converted first into pyruvate and then into glucose by the **gluconeogenic pathway**.

Question 34

Studies have shown that \_\_\_\_\_\_\_, like lactate, is a major precursor of \_\_\_\_\_\_\_ in the liver. The _______ is generated in muscle when the carbon skeletons of some amino acids are used as fuels. The nitrogens from these amino acids are transferred to pyruvate to form \_\_\_\_\_\_\_; the reverse reaction takes place in the liver. This process also helps maintain nitrogen balance.

Answer 34

Studies have shown that **alanine**, like lactate, is a major precursor of **glucose** in the liver. The **alanine** is generated in muscle when the carbon skeletons of some amino acids are used as fuels. The nitrogens from these amino acids are transferred to pyruvate to form **alanine**; the reverse reaction takes place in the liver. This process also helps maintain nitrogen balance.