Fate of Pyruvate

Question 1

what is the net redox yield from glycolysis?

Answer 1

2NADH + 2H+

Question 2

how is redox balance maintained?

Answer 2

only limited NAD+ in a cell
glycolysis reduces it to NADH + H+
NADH re-oxidised to let glycolysis continue
NAD+ regenerated through oxidative metabolism of pyruvate

Question 3

how is NADH involved in oxidative phosphorylation ?

Answer 3

NADH delivers electrons to resp chain

NAD+ then regenerated as electron acceptor for stage 1 (glycolysis) and 2 (krebs) of metabolism

Question 4

where does the TCA cycle occur?

Answer 4

mitochondrial matrix

Question 5

where are the reuired substances for metabolism found?

Answer 5

inner membrane = proteins fro stage 3, ATP synthase, transport proteins
Matrix = TCA cycle enzymes (appart from succinate dehydrogenase)

Question 6

how does pyruvate enter the mitochondrial matrix?

Answer 6

H+ gradient from the cytosol to the matrix

H+/Pyruvate symport (facilitated diffusion)

Question 7

how is pyruvate metabolised to acetyl-CoA in the mitochondrial matrix?

Answer 7

PDC catalyses oxidative decarboxylation of pyruvate to acetyl CoA (irreversible)

Question 8

what is PDC and what does it do?

Answer 8

pyruvate dehydrogenase complex
3 enzymes allosterically regulated by phosphorylation
catalyses conversion of pyruvate to acetyl CoA, activity also determines glucose oxidation

Question 9

what are the reactions catalysed by PDC in the conversion of pyruvate to ACetyl CoA?

Answer 9

1. pyruvate loses CO2 and HETPP is formed
2. hydroxyethyl transferred to lipoic acid and oxidised forming acetyl dihydrolipoamide
3. acetyl group transferred to CoA
4. Dihydrolipoamide reoxidised

Question 10

give a brief overview of the TCA cycle

Answer 10

8 reactions
2C unit condense with 4C unit forming 6C unit
6C unit is decarboxylated twice giving 2CO2
four oxidation reactions occur givin 3NADH + 3H+ and FADH2
one GTP formed (energy)
4C unit reformed

Question 11

how is succinate dehydrogenase formed and where is it found?

Answer 11

succinate + FAD > fumarate + FADH2

found in inner mitochondrial membrane

Question 12

is the TCA cycle involved in anabolism or catabolism?

Answer 12

catabolism

Question 13

what do all products of the stage 2 metabolism have in common?

Answer 13

all can give rise to acetyl CoA and as a result can be oxidised completely to CO2 via TCA

Question 14

what happens with each turn of the TCA cycle?

Answer 14

uptake of 2 carbon atoms in the form of acetyl CoA and release of 2 carbon atoms as CO2
transfer of 3 pairs of electrons to NAD+ forming NADH + H+ and transfer of 1 pair of electrons to reduce FAD to FADH2

Question 15

what happens with each substrate level phosphorylation reaction?

Answer 15

formation of GTP from GDP + Pi

Question 16

how is the TCA cycle controlled?

Answer 16

Plenty energy = high ATP, NADH and acetyl CoA
Lack of energy = High ADP and NAD+
Plenty precursors = high succinyl CoA and acetyl CoA

Question 17

what is the net yield from each glucose molecule?

Answer 17

4 ATP
10 NADH
10 H+
2 FADH2
6 CO2

Question 18

what is pyruvate dehydrogenase complex deficiency?

Answer 18

stage II metabolic disorder
X linked
fatal in males
survivable in carrier females

Question 19

how does pyruvate dehydrogenase complex deficiency present?

Answer 19

largely as neurological disease in children

• poor muscle tone, lack of co-ordination
• retardation and seizures
• persistent lactic acidosis
• respiratory problems

Question 20

what is HLRCC?

Answer 20

hereditary leiomyomatosis and renal cell cancer
defect in fumarase hydratase
multiple systemic benign and malignant tumours (often in kidney)
link between TCA and cell proliferation