Glycolysis and the TCA Cycle

Question 1

What are the 6 types of metabolic reaction?

Answer 1

Redox
Ligation requiring ATP cleavage
Isomerization
Group Transfer
Hydrolytic
Addition or removal of functional groups

Question 2

Where does glycolysis occur?

Answer 2

The cytoplasm/cytosol

Question 3

What is the net gain of ATP and NADH from glycolysis?

Answer 3

2

Question 4

What are the two main aims of glycolysis

Answer 4

Formation and splitting of a high energy compound

Question 5

Why is initially phosphorylating the glucose important?

Answer 5

It makes it more reactive.

It commits it to the subsequent reactions by giving it a negative charge, preventing it from leaving the cell.

Question 6

What enzyme converts Dihydroxyacetone into glyceraldehyde 3-phosphate and why is this important?

Answer 6

TPI (Triose phosphate isomerase) as a deficiency in TPI is the only glycolytic enzymopathy that is fatal, with must sufferers dying within the first 6 years of their life.

Question 7

What are the three fates of pyruvate?

Answer 7

Pyruvate has three main fates:
Alcoholic fermentation
Lactate production
Acetyl CoA production

Question 8

What is alcoholic fermentation characteristic of and under what conditions does it occur?

Answer 8

Alcoholic fermentation is characteristic of yeasts and can occur under anaerobic conditions.

Question 9

How does alcoholic fermentation generate NAD+?

Answer 9

Acetaldehyde (ethanal) is reduced by alcohol dehydrogenase to form ethanol. This oxidises NADH and H+ into NAD+.

Question 10

What is lactate production characteristic of and under what conditions does it occur?

Answer 10

Lactate production is also anaerobic and is characteristic of mammalian muscle during intense activity when oxygen is a limiting factor.

Question 11

How does lactate production generate NAD+?

Answer 11

Pyruvate is converted to lactate by lactate dehydrogenase, oxidising NADH and H+ into NAD+.

Question 12

What is the common purpose behind both alcoholic fermentation and lactate production and why?

Answer 12

Allowing NAD+ to be regenerated and thus glycolysis to continue in conditions of oxygen deprivation, conditions in which the rate of NADH formation by glycolysis is greater than its rate of oxidation by respiratory (electron transport) chain.

Question 13

Apart from lactate production and alcoholic fermentation, what else can happen to pyruvate?

Answer 13

Acetyl CoA can be generated in the mitochondria.

Question 14

What is special about Acetyl CoA?

Answer 14

It is the building block for many important biological molecules.
It has a high energy thioester bond, allowing it to be easily hydrolyzed and so can easily donate its acetate group.

Question 15

What is Beri-Beri a result of?

Answer 15

A deficiency of thiamine (derivative of vitamin B1) leading to poor PDH (pyruvate dehydrogenase complex) function, specifically the thiamine pyrophosphate enzyme.

Question 16

What are the symptoms of Beri-Beri and what organ is particularly vulnerable?

Answer 16

Symptoms include damage to the peripheral nervous system, weakness of the musculature and decreased cardiac output.
The brain is particularly vulnerable due to its heavy reliance on glucose metabolism.

Question 17

What converts pyruvate into acetyl CoA?

Answer 17

PDH (Pyruvate dehydrogenase complex) which is a mixture of enxymes.

Question 18

What does the formation of acetyl CoA also form?

Answer 18

NADH

Question 19

Each turn of the Krebs cycle produces what?

Answer 19

2 CO2 as waste
3 NADH
1 GTP
1 FADH2

Question 20

The Krebs cycle enzymes are all what (apart from one)?

Answer 20

Water-soluble proteins in the mitochondrial matrix.

Question 21

Why is it important that the TCA cycle only occurs in aerobic conditions?

Answer 21

The bulk of ATP is generated when the reduced coenzymes are re-oxidised with the help of oxygen (oxidative phosphorylation).
This re-oxidation means that the TCA cycle only operates under aerobic conditions.

Question 22

Amino acids can also enter the TCA cycle. What must happen to the amino acids first?

Answer 22

Removal of amine group that will later be excreted as urea. The carbon skeleton is then funneled into the production of glucose or fed into the Krebs cycle.

Question 23

Degradation of all twenty amino acids gives rise to what seven molecules?

Answer 23

Pyruvate
Acetyl CoA
Acetoacetyl CoA,
Alpha-ketoglutarate
Fumarate
Oxaloacetate
Succinyl CoA
Acronym to help remember: Proteins And Amino Acids Follow Our Sugars

Question 24

Protein metabolism involves what main reactions?

Answer 24

Transamination reactions.

Question 25

What do transamination reactions consist of?

Answer 25

An amine group is transferred from one amino acid to a keto acid forming a new pair of amino keto acids.

Question 26

NADH produced in glycolysis needs to enter the mitochondria to be utilised by the process of OP and to regenerate NAD+. How does NADH, or more accurately, its high-energy electrons, cross from the cytosol into the matrix of the mitochondria?

Answer 26

The glycerol-phosphate shuttle and the malate-aspartate shuttle.

Question 27

How does the glycerol-phosphate shuttle work?

Answer 27

In the glycerol-phosphate shuttle, electrons from NADH (rather than NADH itself) are carried across the mitochondrial membrane via a shuttle.

Cytosolic glycerol 3-phosphate dehydrogenase transfers electrons from NADH to DHAP to generate glycerol 3-phosphate.

A membrane-bound form of the same enzyme transfers the electrons to FAD. These then get passed to co-enzyme Q, part of the electron transport chain.

Question 28

How does the malate-aspartate shuttle work

Answer 28

Oxaloacetate is converted by MDH (malate dehydrogenase) and NADH into malate which can enter the mitochondria.

In the mitochondria, malate is converted back into oxaloacetate by MDH and NAD+ (which gets turned into NADH, now there is NADH in the mitochondria) which is then converted into aspartate by AT (aspartate transaminase) and glutamate (which gets turned into alpha ketoglutarate).

Aspartate can then leave the mitochondria, where it can be converted by AT and alpha ketoglutarate (which gets turned into glutamate) into oxaloacetate.

Question 29

How much ATP does NADH later produce?

Answer 29

3

Question 30

How much ATP does FADH2 later produce?

Answer 30

2

Question 31

How much ATP does GTP later produce?

Answer 31

1

Question 32

Overall, how much ATP does the oxidation of one acetyl CoA molecule produce (from later OP)?

Answer 32

12
3NADH = 9 ATP
1FADH = 2 ATP
1GTP = 1 ATP

Question 33

What is the link between cancer and TCA enzymes?

Answer 33

Mutations in the TCA genes have been shown to decrease TCA activity and enhance anaerobic glycolysis.
The preferential generation of lactate from glucose even under conditions of ample O2 (Warburg Effect) is characteristic of cancerous cells.