Metabolism

Question 1

Definition of metabolism and common diseases involving it:

Answer 1

All chemical reactions that maintain the living state of cells and organisms

Common diseases involving metabolism:
- Diabetes
- Obesity
- Cancer

Question 2

Features of metabolism

Answer 2

Redox reactions:
- Oxidised: loses electrons
- Reduced: gains electrons

Electron carriers:
- NADPH + H+
- NADH + H+

Glucose oxidises to CO2 and H2O

Question 3

Stages of catabolism of fuel molecules

Answer 3

Glucose:
1. Glucose enters cells
2. Acetyl-CoA production
3. Acetyl-CoA oxidation
4. Electron transfer and oxidative phosphorylation

Question 4

Structure and functions of major carbohydrates

Answer 4

Glucose:
- 6 carbons
- OH on carbon 1

ATP:
- Three phosphate groups
- One ribose sugar
- One base

Question 5

How is glucose transported into the cell?

Answer 5

Via:
- Na+/glucose symporters
- Passive facilitated diffusion glucose transporters

Question 6

Describe glycolysis and name its central intermediate compounds:

Answer 6

Steps:
1. Glucose trapped and destabilised
2. Aldolase generates 2 inter convertible three-carbon molecules
3. Generation of ATP

Compounds:
1. Glucose > fructose-1,6-bisphosphate via 2 ATP
2. Fructose-1, 6-bisphosphate > 2x triose phosphates
3. 2x triose phosphate > 2x pyruvate via via 4 ADP and 2 NAD+

Summary:
Glucose + 2ADP + 2Pi + 2NAD+ —> 2pyruvate + 4ATP + 2H2O + 2NADH + 2H+

Question 7

Key regulatory mechanisms of phosphofructokinase:

Answer 7

Activated by AMP
- Increases glycolysis when energy is needed

Inhibited by:
- ATP: Slows glycolysis when energy is abundant
- Citrate: Slows pyruvate energy to TCA cycle
- H+: Slows glycolysis if too much lactic acid produced

Question 8

Anabolism and catabolism

Answer 8

Anabolism: Assembling of molecules - required energy

Catabolism: Breaking down of molecules to yield energy

Question 9

Lactic acid system:

Answer 9

NADH used to ferment pyruvate to lactic acid

NADH regenerated at beginning of stage 3 of glycolysis

Question 10

Cancer and glycolysis

Answer 10

The Warburg Effect:
Cancer cells produce energy by high rate of glucose metabolism to lactate

Treating cancer:
- 2-deoxygenated-glucose blocks breakdown of G6P
- 3-bromopyruvate blocks production of 1,3 bisphosphoglycerate
- Dichloroacetate promotes conversion of lactic acid to pyruvate

Question 11

Importance of regenerating NAD+

Answer 11

Limited amounts present in cell

NADH must be re-oxidised to NAD+ or glycolysis cannot continue

Regenerated in final stage of glucose catabolism - electron transport chain

Question 12

TCA cycle reactions

Answer 12

Six-carbon unit decarboxylated twice yielding CO2

Four oxidation reactions yields NADH + H+ and FADH2

One GTP formed

4 carbon unit recreated

Question 13

TCA cycle location

Answer 13

Mitochondrial matrix

Exception: Succinate dehydrogenase is in mitochondrial membrane

Question 14

Control in TCA cycle:

Answer 14

High ATP, NADH and acetyl-CoA means plenty of energy

High ADP and NAD+ means lack of energy

High succinyl-CoA and acetyl-CoA means plenty of precursor molecules for biosynthetic reactions

Question 15

Pyruvate in aerobic conditions:

Answer 15

Glycolysis

TCA cycle/PDC:
- Enters mitochondrial matrix via pyruvate transporter (facilitated diffusion)

PDC:
1. Pyruvate loses CO2 and HETPP is formed
2. Hydroxyethyl group transferred to lipoic acid and oxidised to form acetyl dihydrolipoamide
3. Acetyl group transferred to CoA
4. Dihydrolipoamide reoxidised

Question 16

Pyruvate in anaerobic conditions:

Answer 16

Ketone body formation:
- Acetyl CoA diverted to ketones

Oxaloacetate consumed for gluconeogenesis

Fatty acids oxidised to provide energy in absence of glucose

Question 17

Disorders

Answer 17

PDC Deficiency:
- Neurological diastase in children

HLRCC:
- Multiple systematic benign and malignant tumours

Question 18

Electron transport chain

Answer 18

1. Electrons from NADH and FADH2 reduce O2 to H2O
2. Energy of electron transport pumps protons (H+) from mitochondrial matrix to inter membrane space
3. Protons flow back across membrane through transporter linked to ATP synthase down conc. gradient
4. Energy of proton flow phosphorylates ADP to ATP

Question 19

Activation of ATP synthase:

Answer 19

Flow of protons turn rotor causing conformational change

Question 20

ATP synthase structure in the mitochondrion:

Answer 20

F1 subunit in mitochondrial matrix
F0 subunit - hydrophobic, in inner membrane
Stator: a, b, alpha, beta _ subunits
Rotor: c, gamma, _ subunits

Question 21

Sources of ATP generation:

Answer 21

NADH is energy source:
- NADH/FADH2 from TCA made in matrix
- Cannot cross inner mitochondrial membrane
- Shuttles allow energy to be coupled to ATP generators

Question 22

Links between glycolysis, the TCA cycle, and oxidative phosphorylation

Answer 22

2NADH from glycolysis = 1.5 ATP
2NADH from oxidative phosphorylation = 2.5 ATP
2FADH2 = 1.5 ATP
6NADH from citric acid cycle = 2.5 ATP