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Biochemistry and metabolism > Glycolysis and gluconeogenesis > Flashcards

Glycolysis and gluconeogenesis Flashcards

1
Q

What does anabolism and catabolism mean?

A

Anabolism: the synthesis of complex molecules from simpler ones with the energy necessary for synthesis usually being derived from ATP.
Catabolism: the breakdown of energy rich molecules (carbs/lipids/proteins) to simpler ones (CO2/H2O/NH3) with the energy being released being conserved as ATP for use in anabolic reactions.
Theses pathways constitutes a cells metabolism

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2
Q

What are the 3 phases of glycolysis?

A
  1. Energy investment
  2. Cleavage
  3. Energy investment
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3
Q

What is Gibbs free energy defined as in metabolism?

A

The energy derived from the oxidation of dietary fuels.
This energy is transduced into useful work and conserved as metabolites.

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4
Q

In terms of Gibbs free energy what is a exergonic and endergonic reaction?

A

ΔG < 0 , spontaneous exergonic reaction
ΔG > 0, non spontaneous exogenic reaction

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5
Q

What is step 1 of the first phase of glycolysis?

A
  1. Glucose is phosphorylated by hexokinase and ATP to form glucose 6-phosphate + ADP (Endergonic).
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6
Q

What is step 2 of the first phase of glycolysis?

A

Glucose 6-phosphate is isomerised by phosphoglucose isomerase (PGI) / phosphoexose isomerase to form fructose 6- phosphate via acid base catalysis. Δ G of this isomerization is near 0 so the reaction proceed in either direction under physiological conditions.

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7
Q

What is step 3 of the first phase of glycolysis?

A

Phosphorylation of fructose 6-phosphate to fructose 1,6-bisphosphate by phospho-fructokinase-1
(Endergonic)

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8
Q

What is step 4 of the first phase of glycolysis?

A

Fructose 1,6-bisphosphate is cleaved in half by Aldolase to give glyceraldehyde 3- phosphate (this is the one we want) and dihydroxyacetone

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9
Q

What happens after cleavage fructose 1,6-bisphosphate?

A
  1. Dihydroxyacetone is isomerised by triosephosphate isomerase (TPI) to give glyceraldehyde 3-phosphate (GAP).
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10
Q

Give an overview of the first phase of glycolysis.

A

Glucose (6xC) -> 2 x glyceraldehyde 3-phosphate (3xC each)
2 x ATP used

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11
Q

What is step 6 of Glycolysis (2nd phase)

A

GAP is oxidised and phosphorylated to give 1,3 -bisphoshoglycerate by glyceraladerhyde 3-phosphate dehydrogenase. Inorganic phosphate is used as the substrate (instead of ATP) NAD is reduced to NADH as result of oxidation of GAP

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12
Q

What is step 7 of Glycolysis (2nd phase)

A

1,3 -bisphoshoglycerate is used to phosphorylate ADP to ATP by phosphoglycerate kinase to form 3-phosphoglycerate.
2ADP - > 2ATP

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13
Q

What is step 8 of Glycolysis (2nd phase)

A

The position of phosphoryl group of 3-phosphoglycerate is rearranged by phospho-glycerate mutase to give 2-phosphoglycerate.

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14
Q

What is step 9 of Glycolysis (2nd phase)

A

2-phosphoglycerate is dehydrated by Enolase to give Phosphoenolpyruvate.

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15
Q

What is the last step glycolysis?

A

Phosphoenolpyruvate donates the phosphoryl group to ADP to pyruvate kinase to give pyruvate.
2ADP - > 2ATP
This is a high energy exergonic reaction.

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16
Q

What is used as an index to measure the energy status of a cell?

A

Energy charge: related to the concentrations of the adenylate nucleotides?

17
Q

What is the signaling process for energy demand in cells?

A

When ATP is rapidly consumed the enzyme adenylate kinase provides ATP from ADP.
ADP + ADP ⇌ ATP + AMP
This isn’t a very efficient way to produce ATP.
AMP serves as a signal for low energy state and promotes the activity of phosphofructokinase.

18
Q

How does the feedforward regulation of glycolysis work? (in muscle)

A

AMP -> phosphofructokinase promotion -> increased fructose 1,6-bisphosphate which promotes more pyruvate kinase activity = more ATP

19
Q

How is phosphofructokinase affected by ATP?

A

ATP causes a conformational change on phosphofructokinase -> allosteric deactivation (this is reversed by AMP)

20
Q

How is glucose typically transported?

A

Plasma -> glucose transporter -> inside cell
Transmembrane proteins undergo conformational changes to move glucose across the membrane.
Glucose = *
* -> */ -> /*\ -> \/ * (in the cell)

21
Q

How does the affinity of glucose in different tissues vary?

A

Different tissues have different glucose transporters (glut) with different affinities for glucose
High affinity: Erythrocytes, Brain (and others)
Medium affinity: Muscles and Adipose tissue
Low affinity: Liver and Pancreatic cells

22
Q

What does a high affinity for glucose mean practically in different tissues.

A

When plasma has low glucose concentrations (fasting) these tissues will still have glucose uptake.
low mol/L of glucose = high affinity due to concentration gradient

23
Q

Why do erythrocytes have a high demand for glucose.

A

They have no mitochondria (or nucleus)
Rely entirely on glycolysis (hence glucose) occurring in the cytosol for ATP.
ATP to power ion pumps is required for maintaining membrane potential difference to keep biconcave shape.

24
Q

What are the key enzymes involved at the control points of glycolysis. How are they regulated?

A
  1. Hexokinase (phosphorylates glucose)
  2. Phosphofructokinase (phosphorylates phospho 1-fructose)
  3. Pyruvate kinase (makes pyruvate)
    ATP inhibits pyruvate kinase and hexokinase
    AMP increases the activity of Pyruvate kinase and phosphofructokinase
25
Q

What is the first level of glucose regulation?

A

GLUT / glucose transporters via controlling the flow of glucose into the cytoplasm

26
Q

How is hexokinase regulated?

A

It is allosterically inhibited by glucose 6-phosphate (G6P).

27
Q

What is the difference between hexokinase and glucokinase?

A

Glucokinase is the liver’s equivalent of hexokinase (hexokinase found in tissues with high glucose affinity) and has a lower affinity for glucose as the liver is less demanding for glucose. Glucokinase is also inhibited by insulin and fructose 6-phosphate.
Hexokinase: Low km/vmax = high affinity
Glucokinase: High km/vmax = low affinity relative to each other

28
Q

What is the livers unique way of regulating glycolysis?

A

The conversion of phosphoenolpyruvate to pyruvate can be regulated to slow glycolysis by ATP phosphorylation of pyruvate kinase to make innactive phosphorylated pyruvate kinase.
This is done so glucose is not used by the liver and saved for more energy demanding tissues.
When glucose is abundant to enzyme is dephosphorylated via water to allow the liver to store glucose as glycogen.

29
Q

What are the 3 different uses of pyruvate?

A
  1. Anaerobic (lactic fermentation) -> lactate
  2. Aerobic oxidation -> TCA cycle and oxidative phosphorylation
  3. Anaerobic alcoholic fermentation -> ethanol
30
Q

What happens to pyruvate in an oxygen deficit and why?

A

Pyruvate will be pushed to lactic fermentation in order to produce NAD+ for glycolysis

31
Q

What enzyme is used to facilitate the change of pyruvate in anaerobic situations?

A

Lactate dehydrogenase converts pyruvate to lactate (to make NAD+ for glycolysis), the enzyme also facilitates the reverse reaction depending on which substrate is more abundant.

32
Q

What is the cori cycle?

A

When lactate is released into the blood to be transported to the liver where it is converted to pyruvate and then glucose by 6 ATP. This is also known as gluconeogenesis. (also in the kidneys)

33
Q

What substrates can feedback into gluconeogenesis?

A

The end product pyruvate (and oxaloacetate) and the intermediate dihydroxyacetone phosphate.

34
Q

How does pyruvate enter gluconeogenesis?

A

Pyruvate -> oxaloacetate via pyruvate carboxylase -> phosphoenolpyruvate (high energy substrate) via phosphoenolpyruvate carboxylase.
2 x ATP, 1 x NADH and 1 x GTP

35
Q

How is dihydroxyacetone phosphate regenerated for use in gluconeogenesis?

A

Glycerol -> Glycerol phosphate -> DHAP
Glycerol kinase -> glycerol phosphate dehydrogenase
1 x ATP

36
Q

What is the economy for making 1 glucose by gluconeogenesis?

A

3 ATP
1 NADH
1 GTP

Biochemistry and metabolism (7 decks)

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