Gluconeogenesis Flashcards

1
Q

gluconeogenesis definition

A

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

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2
Q

what are the main substrates for gluconeogenesis?

A

lactate, glycerol and amino acids such as alanine and glutamine

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3
Q

what does gluconeogenesis take place?

A

primarily in the liver and partially in the kidney cortex

pathway involves a mitochondrial section and cytosolic section

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4
Q

daily glucose requirements by different organs

A

brain 110g

muscle- 30g

renal medulla- 30g

erythrocytes- 25g

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5
Q

which organs can’t use fatty acids + why?

A

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

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6
Q

how long would our fasting stores last?

A

12 hours

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7
Q

differences between glycolysis and gluconeogenesis

A

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

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8
Q

stages of mitochondrial part of gluconeogenesis

A
  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
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9
Q

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

A

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

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10
Q

stages of cytosolic part of pathway

A
  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
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11
Q

stages of SER part of pathway

A

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

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12
Q

where is glucose 6 phosphatase expressed

A

only expressed in the kidney and liver

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13
Q

what transporter does the glucose travel through?

A

GLUT 2 from SER to blood

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14
Q

how many substrates needed + why?

A

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

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15
Q

how is pyruvate derived during gluconeogenesis?

A

lactate and alanine supplied to the liver from circulation

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16
Q

how is lactate converted to pyruvate?

A

oxidised using NAD to pyruvate, catalysed by lactate dehydrogenase

17
Q

how is alanine converted to pyruvate?

A

catalysed by alanine aminotransferase, with the release of NH3

18
Q

where is lactate produced?

A

produced in anaerobically respiring muscle to reform NAD

19
Q

What is this cycle called + explain?

A

Cori cycle

glycogen broken down to lactate in the muscles

lactate goes to liver where it reforms glucose in gluconeogenesis

20
Q

explain how glutamine is used in gluconeogenesis

A
  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
21
Q

how are triglycerides in adipose used in gluconeogenesis

A
  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
22
Q

why can’t fatty acids be used?

A

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

no net carbons left once reach oxaloacetate

23
Q

3 different ways gluconeogenesis is controlled

A

allosteric control by metabolites- acute

covalent modification by hormones- acute

transcriptional control of gluconeogenic genes/enzymes by hormones - chronic

24
Q

substrates and their enzymes

A

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

25
Q

glucagon and glucocorticoid hormonal affects on transcription

A

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

decreased synthesis of
glucokinase
pyruvate kinase

26
Q

insulin affects on transcription

A
increased synthesis of 
glycogen synthase
hexokinase
phsphofructokinase
pyruvate kinase
decreased synthesis of
pyruvate carboxylase
phosphoenoxypruvate carboxylase
fructose 1,6-bisphosphatase
glucose 6 phosphatase
27
Q

why does gluconeogenesis decrease with prolonged starvation?

A

depletes fat stores, muscle wastage