Gluconeogenesis

Question 1

Gluconeogenesis definition

Answer 1

metabolic pathway synthesising new glucose molecules from non glucose substrates such as lactate, glycerol and some amino acids.
Requires energy

Question 2

What compound must these non carbohydrate precursors be converted into first

Answer 2

pyruvate
(or other intermediates of glycolysis)

Question 3

Conversion of lactate into pyruvate equation

Answer 3

lactate + NAD+ ——–> pyruvate + NADH + H+
catalysed by lactate dehydrogenase
Reversible

Question 4

Conversion of alanine to pyruvate equation

Answer 4

alanine + alpha-ketoglutarate ——> pyruvate + glutamate
catalysed by aminotransferase
Reversible

Question 5

Conversion of glycerol to DHAP equation

Answer 5

glycerol ——> glycerol-3-phosphate (catalysed by glycerol kinase and use of ATP)
glycerol-3-phosphate —-> dihydroxyacetone phosphate (catalysed by glycerol phosphate dehydrogenase and reduction of NAD+)

Question 6

Where does gluconeogenesis occur

Answer 6

mainly in the liver
some in the kidney

Question 7

First reaction in gluconeogenesis
(reactants, products, catalysts)

Answer 7

conversion of pyruvate to phosphoenolpyruvate
catalysed by pyruvate carboxylase and phosphoenolpyruvate carboxykinase

Question 8

first step of converting pyruvate to phosphoenolpyruvate (first reaction gluconeogenesis)

Answer 8

pyruvate + HCO3- + ATP —-> oxaloacetate + ADP + Pi
catalysed by pyruvate carboxylase
pyruvate is carboxylated

Question 9

second step of converting pyruvate to phosphoenolpyruvate (first reaction gluconeogenesis)

Answer 9

oxaloacetate + GTP —> phosphoenolpyruvate + CO2 + GDP
catalysed by phosphoenolpyruvate carboxykinase
oxaloacetate is simultaneously decarboxylated and phosphorylated
PEP is metabolised by the enzymes of glycolysis in reverse

Question 10

Second reaction in gluconeogenesis

Answer 10

fructose 1,6-bisphosphate + H2O —> fructose 6-phosphate + PO3^2-
catalysed by fructose 6-phosphatase

Question 11

terminal reaction in gluconeogenesis

Answer 11

glucose 6-phosphate + H2O —> glucose + PO3^2-
catalysed by glucose 6-phosphatase

Question 12

why dont the last two steps involve the reverse reactions of the glycolysis ones involving kinases

Answer 12

this would involve the thermodynamically unfeasible re-synthesis of ATP from ADP
instead doing a hydrolytic reaction where water releases inorganic phosphate

Question 13

overall equation for gluconeogenesis

Answer 13

2 pyruvate + 6ATP + 2NADH —> glucose + 6Pi + 6ADP + 2NAD+

Question 14

which subcellular compartment is pyruvate carboxylase localised to

Answer 14

mitochondria

Question 15

which subcellular compartment is phosphoenolpyruvate carboxykinase localised to

Answer 15

cytoplasm

Question 16

which subcellular compartment is fructose-1,6-bisphosphatase localised to

Answer 16

cytoplasm

Question 17

which subcellular compartment is glucose-6-phosphatase localised to

Answer 17

endoplasmic reticulum

Question 18

pyruvate enters the mitochondria for carboxylation but oxaloacetate cannot be transported out of the mitochondria.
1. Why?
2. How is this problem overcome?

Answer 18

1. because neither the liver nor kidney have a transporter for oxaloacetate
2. malate dehydrogenase converts oxaloacetate into malate which can be transported into the cytosol. once in the cytosol, malate is converted back into oxaloacetate. NADH is produced which can be used in subsequent reactions

Question 19

5 components of the glucose 6-phosphate transporter in the ER

Answer 19

1. catalytic subunit of glucose 6-phosphatase
2. a calcium binding stabilising protein (SP) involved in catalysis
3. a transporter protein (T1) for glucose 6-phosphate
4. transporter protein (T2) to remove Pi from ER
5. transporter protein (T3) to transport glucose into the cytosol