Metabolism 3- metabolic pathways and ATP production 1

Question 1

What are the 3 principle food molecules in cell metabolism

Answer 1

Polysaccharides: simple sugars
Proteins: amino acids
Fats: fatty acids &
glycerol

Question 2

What basically happens in cellular metabolism

Answer 2

The energy stored in the chemical bonds of food molecules is harnessed and stored in the high energy bonds of ATP.

Question 3

What are the three main stages of cellular metabolism

Answer 3

Glycolysis
TCA
Oxidative phosphorylation

Question 4

What is glycolysis

Answer 4

• Oxidation of glucose within the cytosol of individual cells, generating ATP and NADH.

Question 5

Describe the 6 types of reaction that define metabolism

Answer 5

Oxidation-reduction Electron Transfer
Litigation requiring ATP cleavage Formation of covalent bonds (c-c bonds)

Isomerisation Rearrangement of atoms to give isomers

Group transfer Transfer of one functional group from one molecule to another

Hydrolytic Cleavage of bonds by the addition of water

Addition or removal of functional groups Addition of functional groups to double bonds or the removal of functional groups from double bonds.

Question 6

What happens to the free energy in glucose metabolism

Answer 6

Glucose is metabolised in step series- relatively small activation energies overcome by enzymes and body temp- liberating the free energy of glucose in small quantities and investing it in ATP.

Question 7

Describe, basically, the reaction of glycolysis

Answer 7

1 mole of glucose is converted into 2 moles of pyruvate, generating 2 moles of ATP.
Essentially, there are 2 main steps- formation of high energy compound ( requiring ATP)
Splitting of high energy compound ( releasing ATP).

Question 8

Describe reaction 1 of glycolysis

Answer 8

Glucose is converted into glucose-6-phosphate by a hexose kinase- phosphate group comes from hydrolysis of ATP.

Question 9

What is the importance of reaction 1

Answer 9

This reaction is essentially irreversible and commits the cell to the subsequent reactions. Also traps glucose inside the cell by means of the negative charge- no longer complementary to glucose transporter.

Question 10

Describe reaction 2

Answer 10

Glucose-6-phosphate undergoes an isomerisation reaction and is converted into fructose-6-phosphate by phosphoglucose isomerase.

Question 11

What is the logic behind reaction 2

Answer 11

Allows a highly symmetrical compound to be created- meaning that it can be split easily into two equal halves when cleaved.

Question 12

Describe reaction 3

Answer 12

Fructose-6-phosphate is phosphorylated into fructose-1,6-bisphosphate by phosphofructokinase. Phosphate group comes from hydrolysis of ATP. A highly symmetrical and high energy compound is created.

Question 13

Describe reaction 4

Answer 13

Lysis of fructose-1,6-bisphosphate catalysed by aldolase into 2 highly energetic compounds- glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. The latter cannot continue in glycolysis and needs to undergo further isomerisation reactions.

Question 14

Describe reaction 5

Answer 14

dihydroxyacetone phosphate is converted into glyceraldehyde-3-phosphate by triose phosphate isomerase.

Question 15

Describe reaction 6

Answer 15

2 moles of glyceraldehyde-3-phosphate are converted into 2 moles of 1,3 bisphosphoglycerate by glyceraldehyde
3-phosphate dehydrogenase
2 moles of redNAD produced
Phosphate comes from inorganic phosphate ions.

Question 16

Describe reaction 7

Answer 16

1,3 bisphosphoglycerate is converted into 3-phosphoglycerate by phosphoglycerate kinase. A phosphate group is transferred to ADP, producing ATP.

Question 17

Describe reaction 8

Answer 17

3-phosphoglycerate is converted into 2-phosphoglycerate by phosphoglycerate mutase.

Question 18

Describe reaction 9

Answer 18

2-phosphoglycerate is converted into phosphoenolpyruvate, catalysed by enolase in a dehydration reaction.

Question 19

Describe reaction 10

Answer 19

phosphoenolpyruvate is converted into pyruvate- catalyses by pyruvate kinase- phosphorylating ADP into ATP.

Question 20

Define substrate level phosphorylation

Answer 20

Substrate-level phosphorylation can be defined as the production of ATP by the direct transfer of a high-energy phosphate group from an intermediate substrate in a biochemical pathway to ADP, such as occurs in glycolysis.

Question 21

Describe alcohol fermentation

Answer 21

Pyruvate is converted into acetaldehyde by pyruvate decarboxylase- releasing C02.
Acetaldehyde is converted into ethanol by ethanol dehydrogenase- redNAD converted into NAD.This is the process of anaerobic respiration in yeast.

Question 22

Describe lactate fermentation

Answer 22

Pyruvate is converted into lactate. Catalysed by lactate dehydrogenase. redNAD donates proton to regenerate NAD. Process of anaerobic respiration in mammals.

Question 23

Why is the regeneration of NAD essential

Answer 23

They allow NAD+ to be regenerated and thus glycolysis to continue, in conditions of oxygen deprivation.

i.e. conditions in which the rate of NADH formation by glycolysis is greater than its rate of oxidation by the respiratory chain.

NAD+, you recall, is needed for the dehydrogenation of glyceraldehyde 3-phosphate, which is the first step in generating ATP for the body.

Question 24

Where is lactate dehydrogenase normally found

Answer 24

LDH is present in many body tissues, especially the heart, liver, kidney, skeletal muscle, brain blood cells and lungs.

Question 25

What can elevated levels of lactate dehydrogenase in the plasma be diagnostic of

Answer 25

``` stroke heart attack liver disease (e.g. hepatitis) muscle injury muscular dystrophy pulmonary infarction LDH should not be in the plasma- hence high levels in the plasma indicates tissue damage. ```

Question 26

Describe the importance of creatine phosphate

Answer 26

In muscle, the amount of ATP needed during exercise is only enough to sustain contraction for around one second. Thankfully a large reservoir of creatine phosphate is on hand to buffer demands for phosphate, hence it compensates the loss of ATP by making more ATP. Creatine phosphate --- creatine + ATP reversible reaction

Question 27

How can creatine kinase be used as a diagnostic tool

Answer 27

When a muscle is damaged, creatine kinase leaks into the bloodstream. Either total levels of creatine kinase or the tissue specific isoform can be measured to help to determine which tissue has been damaged Elevated levels can be used to: diagnose myocardial infarction (heart attack) determine the extent of muscular disease evaluate cause of chest pain help discover carriers of muscular dystrophy (Duchenne) The total creatine kinase test is about 70% accurate whilst isoenzyme testing is about 90% accurate.

Question 28

Describe the conversion of lactate into acetyl-coA

Answer 28

Pyruvate + coA --- acetylcoA + CO2. Catalysed by pyruvate dehydrogenase complex- NAD converted into redNAD. The acetyl CoA thus formed is committed to entry into the citric acid cycle and can ultimately produce ATP by the process of oxidative phosphorylation

Question 29

What does the pyruvate dehydrogenase complex consist of

Answer 29

3 enzymes and 5 cofactors.

Question 30

What are the 5 cofactors

Answer 30

Thiamine pyrophosphate (TPP), lipoamide, FAD, CoA and NAD+.

Question 31

What are the three enzymes in the pyruvate dehydrogenase complex

Answer 31

pyruvate decarboxylase lipoamide reductase- transacetylase dihydrolipoyl dehydrogenase

Question 32

Describe the characteristics of Thiamine pyrophosphate

Answer 32

Derivative of vitamin B1. Readily loses a proton and the resulting carbanion attacks that of pyruvate to yield hydroxyethyl-TPP. A deficiency of thiamine (vitamin B1) is the cause of Beri-Beri, whose symptoms include damage to the peripheral nervous system, weakness of the musculature and decreased cardiac output. The brain is particularly vulnerable as it relies heavily on glucose metabolism.

Question 33

Describe the characteristics of lipoamide

Answer 33

``` Functional group (undergoes oxidation and reduction). The long flexible arm of the molecule allows the dithiol group to swing from one active site to another within the complex. ``` Arsenite (AsO33-) and mercury have a high affinity for neighbouring sulphydryl groups, such as those that occur in reduced lipoamide and will readily inhibit pyruvate dehydrogenase.

Question 34

Describe the characteristics of FAD

Answer 34

FAD accepts and donates 2 electrons with 2 protons

Question 35

Explain how the pyruvate dehydrogenase complex functions

Answer 35

Decarboxylation of pyruvate to give hydroxyethyl TPP. Oxidation & transfer to lipoamide to give acetylipoamide. Transfer of the acetyl group to CoA to give acetyl CoA. Regeneration of oxidised lipoamide. Regeneration of oxidised FAD, generating NADH.

Question 36

Describe the role of glucose metabolism in cancer

Answer 36

Glucose is rapidly metabolised to lactate by aggressive tumour cells and the high uptake of glucose is the basis for [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging of tumours Cancer cells undergo selective reprogramming and use several mechanisms to increase the flux of glucose in glycolysis to aid tumour growth: Increased expression of glucose transporters (e.g. GLUT1) Increased expression of hexokinase and phosphofructokinase.