2.1 - Cell Metabolism 1

Question 1

Types of reactions that define metabolism

Answer 1

• Oxidation-reduction - electron transfer
• Ligation requiring ATP cleavage - formation of covalent bonds
• Isomerisation - rearrangement of atoms to form isomers
• Group transfer - transfer of a 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 their removal to form double bonds

Question 2

Glycolysis - main concepts

Answer 2

• Essentially an anaerobic process occurring in the cytoplasm
• Involves formation of a high energy compound (uses ATP), and the splitting of a high energy compound (generates ATP)

Question 3

Glycolysis step 1

Answer 3

Glucose —> glucose-6-phosphate (+ H+)

• hexokinase
• group transfer
• requires one ATP —> ADP
• essentially irreversible reaction that commits the cell to subsequent reactions and traps glucose inside the cell by means of the negative charge (can no longer fit through glucose transporters)

Question 4

Glycolysis step 2

Answer 4

Glucose-6-phosphate —> fructose-6-phosphate

• phosphoglucose isomerise
• isomerisation

Question 5

Glycolysis step 3

Answer 5

Fructose-6-phosphate —> fructose-1,6-biphosphate

• phosphofructokinase
• group transfer
• requires one ATP —> ADP
• regulation of phosphofructokinase is a key control step for the entry of sugars into the glycolysis pathway

Question 6

Glycolysis step 4

Answer 6

Fructose-1,6-biphosphate —> glyceraldehyde-3-phosphate + dihydroxyacetone phosphate

• aldolase
• hydrolytic
• DHAP cannot undergo glycolysis so needs to be converted

Question 7

Glycolysis step 5

Answer 7

Dihydroxyacetone phosphate —> glyceraldehyde-3-phosphate

• triose phosphate isomerase (TPI)
• isomerisation
• deficiency in TPI is the only glycolysis enzymopathy that is fatal - as too little ATP is made if only half the glucose is metabolised

Question 8

Glycolysis step 6

Answer 8

(2x) glyceraldehyde-3-phosphate —> 1,3-biphosphoglycerate

• glyceraldehyde-3-phosphate dehydrogenase
• redox and group transfer
• NAD+ + Pi —> NADH (generates more ATP later)

Question 9

Glycolysis step 7

Answer 9

1,3-biphosohoglycerate —> 3-phosphoglycerate

• phosphoglycerate kinase
• group transfer (of high energy phosphate group to ADP - kinases transfer phosphate groups to molecules)
• ADP —> ATP = energy out

Question 10

Glycolysis step 8

Answer 10

3-phosphoglycerate —> 2-phosphoglycerate

• phosphoglycerate mutase
• isomerisation

Question 11

Glycolysis step 9

Answer 11

2-phosphoglycerate —> phosphoenolpyruvate + H2O

• enolase
• group removal / dehydration

Question 12

Glycolysis step 10

Answer 12

Phosphoenolpyruvate —> pyruvate

• pyruvate kinase
• group transfer
• ADP —> ATP

Question 13

Net result of glycolysis

Answer 13

• 2 ATP molecules + 2 NADH molecules (can generate ATP)
• remember each reaction after step 5 happens twice as two glyceraldehyde-3-phosphate molecules are made

Question 14

Fates of pyruvate - alcoholic fermentation

Answer 14

Pyruvate —> acetaldehyde

• pyruvate decarboxylase
• H+ —> CO2

Acetaldehyde —> ethanol

• alcohol dehydrogenase
• NADH + H+ —> NAD+
• anaerobic conditions, characteristic of yeasts
• regenerates NAD+ = glycolysis can continue in conditions of oxygen deprivation (needed for dehydrogenation of G3P which is the first step in generating ATP)

Question 15

Fates of pyruvate - generation of lactate

Answer 15

Pyruvate —> lactate

• lactate dehydrogenase
• NADH + H+ —> NAD+
• redox: NADH oxidised, pyruvate reduced
• anaerobic, characteristic of mammalian muscle during intense activity when oxygen is a limiting factor
• regenerates NAD+ = glycolysis can continue in conditions of oxygen deprivation (needed for dehydrogenation of G3P which is the first step in generating ATP)

Question 16

Creatine phosphate as a buffer for ATP

Answer 16

Creatine phosphate <—> creatine + ATP

• creatine kinase
• ADP + H+ —> ATP
• in the muscle, the amount of ATP needed during exercise is only enough to sustain contraction for a second, so a large reservoir of creatine phosphate is on hand to buffer demands for phosphate

Question 17

Fates of pyruvate - acetyl CoA generation

Answer 17

Pyruvate + CoA —> acetyl CoA + CO2

• pyruvate dehydrogenase complex (PDH)
• NAD+ —> NADH
• occurs in the mitochondria
• acetyl CoA formed is committed to entry into the TCA cycle
• Acetyl CoA (C-S bond, ribose, phosphate, adenine): the thioester bond is a high-energy linkage so is readily hydrolysed, enabling 2C acetyl group to be donated to other molecules

Question 18

Beri-Beri

Answer 18

• results from poor PDH function
• a deficiency of thiamine is the cause of Beri-Beri, whose symptoms include damage to the PNS, weakness of the musculature and decreased cardiac output
• the brain is vulnerable as it relies heavily on glucose metabolism
• thiamine pyrophosphate is a cofactor of the PDH complex, it readily loses a proton and the resulting carbanion attacks pyruvate