Metabolism and its control Flashcards

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1
Q

Metabolism

A

The chemical processes that occur within a living organism in order to maintain life. Composed of anabolism (building up of complex molecules, requiring energy) and catabolism (breaking down into simple molecules, releasing energy).

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2
Q

Metabolic pathways

A

Starts with a specific metabolite, which undergoes a chain of enzymatically catalysed reactions to form a product. Metabolic pathways interconnect to form networks.

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3
Q

Redox reactions

A

Oxidation is loss of electrons (acquisition of oxygen), reduction is gain of electrons (loss of oxygen. Redox reactions are usually coupled due to electron transfer between molecules.

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4
Q

Types of metabolic reaction

A
  • hydrolysis/dehydration is the addition/removal of water
  • (de)phosphorylation is the removal/addition of a phosphate group
  • (de)carboxylation is the removal/addition of a CO2 molecule
  • ligation reactions involve the binding of molecules
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5
Q

Adenosine triphosphate

A

ATP is the energy currency of the cell, storing energy in 2 phosphoanhydride bonds. Hydrolysis of these bonds releases 7.3 kcal of energy. A constant supply of ATP is required for all cell processes eg. growth.

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6
Q

ATP production

A

ATP can be produced through substrate-level phosphorylation (anaerobic) or oxidative phosphorylation (aerobic). The steps involved in ATP production are:

  • Glycolysis
  • Oxidative decarboxylation
  • Krebs/TCA cycle
  • Electron transport chain
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7
Q

Glycolysis

A

Glycolysis occurs in the cytoplasm and involves two stages:
1) Priming step (energy investment)- two phosphorylation and one isomerisation reaction converts glucose into fructose-1,6-bisphosphate.
2) Splitting step (energy generation)- redox and dephosphorylation reactions convert two glyceraldehyde-3-phosphate molecules into two pyruvate molecules
The overall yield per 1 glucose is 2 pyruvate, 2ATP and 2NADH.

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8
Q

Anaerobic respiration

A

In the absence of oxygen, NAD+ cannot be regenerated during the electron transport chain. Pyruvate is converted into lactic acid and CO2 to replenish the NAD+ instead.

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9
Q

The Cori cycle

A

During times of low oxygen availability (ie. high exercise), the lactate produced by the muscles during anaerobic respiration is used by the liver to make glucose. In gluconeogenesis, lactate is converted back into pyruvate which is converted to glucose, involving reactions similar to the reverse of glycolysis. This process costs energy.

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10
Q

Pyruvate decarboxylation

A

In the mitohondria, pyruvate is converted into acetyl-CoA (an activated carrier of 2-carbon fragments) by a large, tightly regulated enzyme complex called pyruvate dehydrogenase (PDH). 1 NAD+ is reduced to NADH and one CO2 is produced per pyruvate. This process generates acetyl- CoA to enter the TCA cycle.

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11
Q

The Krebs (TCA) cycle

A

Involves the oxidative decarboxylation of carbon originating from oxaloacetate, which is replenished by acetyl-CoA. Occurs in the mitochondrial matrix and results in the generation of 3NADH and 1FADH2 per cycle, storing energy within these reduced electron carriers. 2 CO2 molecules are produced per cycle.

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12
Q

NAD+

A

A hydrogen carrier derived from niacin (vitamin B3) which acts as a coenzyme in redox reactions. Its oxidation generates 2.5 ATP molecules.

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13
Q

FAD

A

A hydrogen carrier derived from riboflavin (vitamin B2) which acts as a prosthetic group, and is contained within succinate dehydrogenase. Its oxidation generates 1.5 ATP molecules.

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14
Q

Electron transport chain

A

A series of enzymes located in the inner mitochondrial membrane, which use the energy from oxidising electron carriers to pump protons into the intermembrane space. The proton gradient is used to drive ATP synthase, generating ATP.

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15
Q

Final electron acceptor

A

Oxygen acts as the final electron acceptor on the electron transport chain, being converted into water in a reaction catalysed by cytochrome c oxidase (complex IV).

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16
Q

Substrate level phosphorylation

A

The direct transfer of phosphate from a substrate to ATP.

17
Q

Oxidative phosphorylation

A

The formation of ATP coupled to the oxidation of NADH or FADH2 by oxygen.

18
Q

Oxidation of cytosolic NADH

A

NADH molecules formed during glycolysis are located in the cytosol. They can only be oxidised inside the mitochondria, but are unable to cross the mitochondrial membrane. Two mechanisms enable their transfer;

  • the glycerol phosphate shuttle
  • the malate/aspartate shuttle.
19
Q

Glycerol phosphate shuttle

A
  • uses cytosolic NADH to reduce DHAP
  • forms glycerol-3-phosphate
  • diffuses into the mitochondria
  • oxidised by mitochondrial glycerol-3-phosphate dehydrogenase
  • forms DAHP and FADH2
20
Q

Malate/aspartate shuttle

A

-starts with cytosolic oxaloacetate
-reduced by malate dehydrogenase to form malate
-transported into the mitochondria
-reaction is reversed by mitochondrial malate dehydrogenase
OAA is unable to cross the inner mitochondrial membrane, so it is transaminated to aspartate (which can be transported to the cytosol) and converted back into OAA by cytosolic aspartate amino transferase.

21
Q

Control of metabolism

A

3 major control strategies:

  • enzyme levels
  • enzyme activity
  • substrate availability
22
Q

Control enzymes

A
  • GLUTs= glucose transporters
  • phosphofructokinase (PFK); switches on glycolysis
  • pyruvate dehydrogenase, isocitrate dehydrogenase, a-ketoglutarate dehydrogenase; control the TCA cycle
23
Q

Metabolic profiles of organs

A
  • Brain: consumes 60% of glucose at rest, can use ketone bodies in starvation
  • Muscle: uses fatty acids at rest, uses glucose during exercise, uses glycogen stores in anaerobic respiration
  • Kidneys: use 10% of glucose
  • Liver: major site of conversion
24
Q

Diseases due to defects in carbohydrate metabolism

A
  • diabetes
  • beriberi, mercury and arsenic poisoning
  • mitochondrial defects
  • cancer
  • glycogen storage disease