Gluconeogenesis

Question 1

gluconeogenesis definition

Answer 1

a metabolic pathway that results in the synthesis of glucose from certain non carbohydrate substrates

Question 2

what are the main substrates for gluconeogenesis?

Answer 2

lactate, glycerol and amino acids such as alanine and glutamine

Question 3

what does gluconeogenesis take place?

Answer 3

primarily in the liver and partially in the kidney cortex

pathway involves a mitochondrial section and cytosolic section

Question 4

daily glucose requirements by different organs

Answer 4

brain 110g

muscle- 30g

renal medulla- 30g

erythrocytes- 25g

Question 5

which organs can’t use fatty acids + why?

Answer 5

brain, renal medulla and red blood cells

fatty acids bound to albumin cannot pass the blood-brain barrier

breaking down fatty acids requires a lot of ATP, and thus more oxygen and thus more superoxides and oxidative stress

Question 6

how long would our fasting stores last?

Answer 6

12 hours

Question 7

differences between glycolysis and gluconeogenesis

Answer 7

some enzymes in glycolysis are irreversible, so need different enzymes

energy input for gluconeogenesis exceeds reversed glycolysis, 6 ATP vs 2

different control mechanisms

involves mitochondria, not just the cytosol

Question 8

stages of mitochondrial part of gluconeogenesis

Answer 8

1. pyruvate to oxaloacetate, catalysed by pyruvate carboxylase, using ATP
2. oxaloacetate reduced to malate using NADH and catalysed by malate dehydrogenase
3. malate diffuses across mitochondrial inner membrane
4. malate oxidised to oxaloacetate, forming NADH and catalysed by malate dehydrogenase
5. phosphoenolpyruvate carboxykinase catalyses oxaloacetate to phosphoenolpyruvate using GTP

Question 9

why does this long-winded mitochondrial pathway need to take place?

Answer 9

in glycolysis phosphoenolpyruvate to pyruvate is catalysed by pyruvate kinase in an irreversible reaction, so cannot just back track

oxaloacetate cannot diffuse through membrane, so malate has to be formed

Question 10

stages of cytosolic part of pathway

Answer 10

1. phosphoenolpyruvate to 2-phosphoglycerate catalysed by enolase
2. 2 phosphoglycerate to 3 phosphoglycerate catalysed by phosphoglycerate mutase
3. 3-phosphoglycerate to 1,3 biphosphoglycerate catalysed by phosphoglycerate kinase using ATP
4. 1,3-biphosphoglycerate to glyceraldehyde 3 phosphate catalysed by glyceraldehyde 3 phosphate dehydrogenase using NADH
5. glyceraldehyde 3 phosphate to dihydroxyacetone phosphate catalysed by triose phosphate isomerase
6. glyceraldehyde 3-phosphate and dihydroxyacetone phosphate to fructose 1,6- diphosphate catalysed by aldolase
7. fructose 1,6-bisphosphate to fructose 6 phosphate, catalysed by fructose 1,6-bisphosphatase
8. fructose 6 phosphate to glucose 6 phosphate catalysed by phosphoglucose isomerase

Question 11

stages of SER part of pathway

Answer 11

glucose 6 phosphatase catalyses the conversion of glucose 6 phosphate to glucose

Question 12

where is glucose 6 phosphatase expressed

Answer 12

only expressed in the kidney and liver

Question 13

what transporter does the glucose travel through?

Answer 13

GLUT 2 from SER to blood

Question 14

how many substrates needed + why?

Answer 14

need two pyruvates, double everything up prior to glyceraldehyde 3 phosphate, as this needs to be converted to dihydroxyacetone phosphate and then react with itself

4 ATPs

4 NADH

2 GTP

2 PYRUVATES

Question 15

how is pyruvate derived during gluconeogenesis?

Answer 15

lactate and alanine supplied to the liver from circulation

Question 16

how is lactate converted to pyruvate?

Answer 16

oxidised using NAD to pyruvate, catalysed by lactate dehydrogenase

Question 17

how is alanine converted to pyruvate?

Answer 17

catalysed by alanine aminotransferase, with the release of NH3

Question 18

where is lactate produced?

Answer 18

produced in anaerobically respiring muscle to reform NAD

Question 19

What is this cycle called + explain?

Answer 19

Cori cycle

glycogen broken down to lactate in the muscles

lactate goes to liver where it reforms glucose in gluconeogenesis

Question 20

explain how glutamine is used in gluconeogenesis

Answer 20

1. glutamine from muscles converted to glutamate with the release of NH3
2. glutamate to alphaketoglutarate with the release of NH3
3. joins the Krebs cycle to form malate and then goes through same process as before

Question 21

how are triglycerides in adipose used in gluconeogenesis

Answer 21

1. form glycerol and fatty acids
2. glycerol produces glycerol 3-phosphate
3. glycerol 3-phosphate to dihydroxyacetone phosphate
4. dihydroxyacetone phosphate to fructose 1,6-bisphosphate
5. joins the pathway

Question 22

why can’t fatty acids be used?

Answer 22

acetyl CoA is 2C and 2 carbon dioxide molecules lost in TCA, which means two carbons gone

no net carbons left once reach oxaloacetate

Question 23

3 different ways gluconeogenesis is controlled

Answer 23

allosteric control by metabolites- acute

covalent modification by hormones- acute

transcriptional control of gluconeogenic genes/enzymes by hormones - chronic

Question 24

substrates and their enzymes

Answer 24

citrate and glucagon indirectly increase fructose 1,6 bisphosphate activity

glucagon increases phosphoenolpyruvate carboxykinase activity

acetyl CoA increases pyruvate carboxylase activity

glucagon decreases pyruvate kinase activity

Question 25

glucagon and glucocorticoid hormonal affects on transcription

Answer 25

increase synthesis of pyruvate carboxylase phosphoenolpyruvate carboxykinase fructose 1,6-bisphosphatase glucose 6-phosphatase decreased synthesis of glucokinase pyruvate kinase

Question 26

insulin affects on transcription

Answer 26

``` increased synthesis of glycogen synthase hexokinase phsphofructokinase pyruvate kinase ``` ``` decreased synthesis of pyruvate carboxylase phosphoenoxypruvate carboxylase fructose 1,6-bisphosphatase glucose 6 phosphatase ```

Question 27

why does gluconeogenesis decrease with prolonged starvation?

Answer 27

depletes fat stores, muscle wastage