Metabolism L3.1

Question 1

Diagram showing overview of Catabolism

Answer 1

Question 2

State location of glycolysis

Answer 2

Cytosol

Question 3

Describe the end of stage 2 catabolism

Answer 3

Pyruvate (end product of aerobic glycolysis) does not directly enter TCA cycle (stage 3 catabolism)

Pyruvate must be transported from cytosol to mitochondria via PYRUVATE TRANSLOCASE

(In mitochondrial matrix, pyruvate converted to acetyl CoA)

Question 4

Describe how pyruvate is converted into acetyl CoA in mitochondrial matrix during end of stage 2 catabolism

Answer 4

Pyurvate undergoes oxidative decarboxylation
(IRRERVSIBLE) by pyruvate dehydrogenase

Question 5

State cofactors required by pyruvate dehydrogenase

Answer 5

Thiamine phosphate
FAD
NAD+
CoA
Lipoic acid

Question 6

State the source of cofactors required by pyruvate dehydrogenase

Answer 6

Vitamin B (B1, b3, B5)

Question 7

State why converstion of pyruvate to Acetyl CoA is sensitive to vit B deficiencies

Answer 7

Pyruvate to Acetyl Coa = oxidative decarboxylation reaction by Pyruvate Dehydrogenase
This enzyme requires cofactors, (thiamine, CoA, NAD+, FAD)
These cofactors are provided from Vit B (B3, B5)

Question 8

Diagram showing regulation of reaction catalysed by Pryuvate Dehydrogenase

Answer 8

Question 9

How is PDH regulated (activated and inhibited) during conversion of pyruvate to acetyl CoA

Answer 9

Activated by:

1. Pyruvate
2. CoA
3. NAD+
4. ADP
5. Insulin

Inhibited by:
1. Aceytol CoA
2. ATP
3. NADH+ + H+

Question 10

State cause of Pyruvate Dehydrogenase Deficiency

Answer 10

Genetic defect in pyruvate dehydrogenase

Question 11

State effects of pyruvate dehydrogenase deficiency

Answer 11

No acetyl CoA
So, no energy release in aerobic metabolim
To compensate, anaerobic metabolism occurs, (reduction of pyruvate to lactate), too much lactate then accumulates in blood, leads to LACTIC ACIDOSIS

Question 12

Lactic acidosis recap

Answer 12

Question 13

State where TCA cycle occurs

Answer 13

Mitochondria

Question 14

Summary of TCA cycle

Answer 14

Question 15

Diagram showing TCA cycle

Answer 15

Only memorise important reactions

Question 16

Diagram showing TCA cycle: GTP (ATP) synthesis + reducing power release

Answer 16

Question 17

Why are there 2 x TCA cycles per mole of glucose?

Answer 17

For each mole of glucose, 2 moles of pyruvate are produced in glycolysis.

Therefore, the 2 pyruvates are both oxidatvely decarboxylised into Acetyl CoA molecules.

So, 2 x Acetyl CoA, therefore, 2 rounds of TCA cycle

Question 18

Stage 1 of TCA Cycle

Answer 18

Acetyl CoA (2C) undergoes condensation with oxaloacetate (4C) to form citrate (6C)

CITRATE SYNTHASE

Question 19

Stage 4 of TCA Cycle

Answer 19

Oxidative decarboxylation of isocitrate (6C) to form alpha-ketoglutarate (5C)

ISOCITRATE DEHYDROGENASE

NADH + H+ produced

Question 20

Stage 5 of TCA cycle

Answer 20

Oxidative decarboxylation of alpha-ketoglutarate to form succinyl-CoA (4C)
(alpha-ketoglutarate dehydrogenase)

NADH + H+ produced

Question 21

Stage 6 of TCA cycle

Answer 21

Succinyl-CoA cleaved to form
1. Succinate
2. CoA
by subtsrate phosphorylation

THIOKINASE

(GTP formed)

Question 22

Stage 7 of TCA cycle

Answer 22

Oxidation of succinate to fumerase

Succinate Dehydrogenease
FADH2 produced

Question 23

Stage 8 of TCA cycle

Answer 23

Fumerate hydrated to malate

FUMERASE

Question 24

Stage 9 of TCA cycle

Answer 24

Malate oxidised to oxaloacertate

Malate dehydrogenease

NADH + H+ produced

Question 25

State points of regulation within TCA cycle

Answer 25

Reactions 1,4, 5 1. Citric synthase Activated: Acetyl CoA Inhibited: Citrate 2. Isocitrate dehydrogenase Activated: ADP Inhibited: ATP, NADH + H+ 5. alpha-ketoglutarate dehydrigenase Activated: ADP Inhibited: ATP, NADH + H+, succinyl CoA

Question 26

TCA cycle provides intermediates for anabolic processes

Answer 26

Question 27

State the location of oxidative phoshorylation

Answer 27

Mitochondria (inner mitochondrial membrane)

Question 28

State conditions required for oxidative phosphorylation

Answer 28

O2

Question 29

Summarise oxidative phosphorylation

Answer 29

Electrons from NADH+ + H+ and FADH2 transferred to O2. The carriers above are now re-oxidised to NAD+, FAD) Free energy from electron transport drives synthesis of ATP

Question 30

Describe oxidative phosphorylation

Answer 30

2 phases: 1. Electron transport 2. ATP synthesis Electrons transferred from NADH+ + H+ and FADH2 through series of protein complexes to O2 (IN MORE DETAIL: PCI + PCII pass electrons from NADH+ + H+ and FADH2 TO PCIII and PCIV. PCIV passes electrons to oxygen, which forms water). PCI, PCIII, PCIV pump H+ from matrix to intermembrane space using free energy released during electron transport) This releases energy 30% of this energy used to move H+ across membrane and rest is lost as heat Movement of H+ creates H+ conc gradient cross inner membrane (proton motive force) H+ conc gradient dissipated (reduced) by ATP synthase H+ pumped into matrix (favoured by electrochemical gradient) Energy released from flow of H+ used by ATP synthase to synthesise ATP from ADP and Pi.

Question 31

Energetics of oxidative phosphorylation

Answer 31

Question 32

Question 33

Describe the net synthesis of ATP from glucose

Answer 33

Question 34

Compare oxidative vs substrate level phosphorylation

Answer 34

Question 35

Describe Regulation of oxidative phosphorylation

Answer 35

High ATP - Rate of oxidative phosphorylation decreased. No substrate for ATP synthase. Conc. of H+ atoms No, inward flow of H+ atoms stops. Prevents firther H+ pump, stops electron transport Low ATP - Rate of oxidative phosphorylation increased

Question 36

Describe what factors affect the efficiency of oxidative phosphorylation

Answer 36

Tightness of coupling og electron transport to ATP synthesis. Coupling depend s on tissues: - Higher in tissues with higher energy demand (exercising muscle tissue) Uncoupling occurs in brown adipose tissue. Therefore, oxidative phosphorylation is less efficient This allows extra heat generation rather than ATP

Question 37

State conditions under which oxidative phosphorylation can be inhibited

Answer 37

1. Anaerobic 2. Excessive reactive oxygen species 3. Cabron monoxide, cyanide (inhibit electron transport) Cyanide - prevents acceptance of electrons by O2 therefore, no electrochemical gradient across mitochondrial membrane, no ATP synthesis Leads to death

Question 38

State the role of synthetic uncouplers

Answer 38

e.g. 2,4 dinitrophenol (DNP) (uncoupling electron transport from ATP synthesis) 1. Increase permeability of mitochondrial inner membrane to H+ 2. Dissipates H+ conc gradient 3. No movement of H+ / No proton motive force 4. Uncouples electron transport from ATP synthesis 5. No ATP synthesis,increased heat production, leads to death

Question 39

Why was DNP used medically as a weight loss drug?

Answer 39

Increased metabolic rate, increase heat production

Question 40

Why was DNP banned from human consumption?

Answer 40

e.g. 2,4 dinitrophenol (DNP) (uncoupling electron transport from ATP synthesis) 1. Increase permeability of mitochondrial inner membrane to H+ 2. Dissipates H+ conc gradient 3. No movement of H+ / No proton motive force 4. Uncouples electron transport from ATP synthesis 5. No ATP synthesis,increased heat production, leads to death

Question 41

Describe the process of uncoupling in brown adipose tissue

Answer 41

Brown adipose tissue has UCP1 (uncoupling protein - thermogenin) (present in inner mitochindrial membrane) UCP-1 activated in response to cold / stress 1. Noradrenaline released from sympathetic nervous system 2. Binds to beta adrenergic receptros on BAT 3. Stimulates hydrolysis of triacylglycerols relasing fatty acids 4. Fatty acids oxidised in mitochondria, providing reducing power for oxidatiove phosphorylation 5. Fatty acids activate UCP1, transports H+ from intermembane space into matrix, but no ATP synthesis 6. Electron transport uncoupled from ATP synthesis. Energy from dissipation of H+ conc gradient used to generate heat This process is known as NON-SHIVERING THERMOGENESIS.

Question 42

State causes of oxidative phosphorylation diseases

Answer 42

Mutations in mitochondrial DNA (greater mutation rate than nuclear DNA)

Question 43

State causes and symptoms of Leber hereditary optic neuropathy (LHON)

Answer 43

Mutation in gene coding for PTC 1 Presnets with loss of vision

Question 44

State causes and symptoms of Leigh syndrome (subacute necrotising encephalopathy)

Answer 44

Mutation in gene coding for ATP synthase Presents with progressive loss of mental and physical abilities in infancy