L18 Bioenergetics Flashcards

1
Q

What is the structure of the mitochondrial inner membrane?

A
  • Folded into cristae which protrude into the matrix of the mitochondria.
  • Permeable to a small number of molecules only via specific transporters - allows the mitochondrial matrix to have entirely different concentrations to the cytosol. It allows compartmentalisation.
  • Contains more protein than lipid – respiratory enzymes, transporter proteins that are present.
  • A very good electrical insulator - This is due to cardiolipin a phospholipid in the membrane which is important to maintain the gradient.
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2
Q

What is the structure of the mitochondrial outer membrane?

A
  • Smooth and freely permeable to molecules under 5000 Da including ions. This is due to pore proteins called Porins proteins which allow these molecules to move.
  • No ionic or electrical gradients
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3
Q

What is found in the matrix of the mitochondrion?

A

• Contains wide range of enzymes – Krebs cycle, fatty acid oxidation, urea cycle (in liver)
• High concentrations of substrates, cofactors & ions
Contains mitochondrial DNA, RNA & ribosomes (these resemble bacterial components) though few mitochondrial proteins are coded on mitochondrial DNA. Ribosomes resemble those in prokaryotes (symbiosis). A very small proportion of the total number of proteins in mitochondria are coded by mitochondrial DNA. A large proportion are coded in the nucleus.

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4
Q

What is found in the inter membrane space?

A

• Has metabolite & ion concentrations similar to cytosol due to relatively free movement between the two.
Contains Cytochrome C.

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5
Q

Give details of the link reaction.

A

After glycolysis, pyruvate move from the cytosol into the inner membrane space to the mitochondrial membrane and is converted to acetyl CoA via the link reaction.
Pyruvate dehydrogenase requires TPP as a cofactor - Thiamine pyrophosphate. Thiamine is Vitamin B1.

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6
Q

What is Wernicke-Kirsakoff syndrome?

A

Lack of thiamine seen in alcohol addicts can cause Wernicke-Korsakoff syndrome. Alcohol affects the absorption of B1 in the diet. Alcoholism often leads to chaotic lives and poor dietary choices, leading to thiamine deficiency. WKS leads to memory loss - it is a neurological disease. This can occur acutely if you give an alcoholic with lots of alcohol but not thiamine.

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7
Q

What is the key control point in metabolism of the link reaction?

A

Pyruvate dehydrogenase is controlled through phosphorylation. Pyruvate dehydrogenase kinase phosphorylases the enzyme and deactivates it. Pyruvate dehydrogenase phosphatase removes a phosphate from it and activates the reaction. Phosphorylation is promoted by signals of high energy - NADH, ATP, Acetyl CoA. This will therefore decrease the movement of pyruvate to Acetyl CoA .

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8
Q

What are the products of the Krebs’ cycle?

A

The key output:

  • NADH
  • FADH2
  • Waste product - carbon dioxide
  • GTP
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9
Q

Give the main steps of the Krebs’ cycle.

A

Acetyl CoA then reacts with oxoacetate to produce citrate. Loss of the 2 additional carbons as carbon dioxide producing a 4C compound - Succinyl CoA. Oxidation of succinyl-CoA forms oxoacetate to allow another round of the reaction.

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10
Q

What are the control points of the Krebs’ cycle?

A

Control of the Kreb’s cycle:
- Incorporation of acetyl-CoA to oxoacetate is inhibited by ATP, NADH and succinyl-CoA and citrate (product inhibition).
- High levels of isocitrate dehydrogenase is inhibited by ATP, NADH and stimulated by ADP and NAD+. Speeded up when you need energy and slowed down when you don’t need it.
Control of cycle by need for energy as monitored mainly by ATP: ADP and NADH: NAD+ ratios

Key enzymes
citrate synthase
isocitrate dehydrogenase
α-ketoglutarate dehydrogenase

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11
Q

How can the Krebs’ cycle act as an exchange for intermediates?

A

The Kreb’s cycle acts as an exchange for intermediates for other metabolic pathways. Amino acid carbon skeletons feed into the Kreb’s cycle. A number of anabolic synthesis use Kreb’s cycle intermediates as building blocks. Synthesis of oxaloacetate from pyruvate is important in replenishing oxaloacetate if needed.

In synthesis of amino acids alpha-ketoglutarate and oxaloacetate are important precursors for amino acids.
Citrate can be transported into the cytosol to make cholesterol and fatty acids.
Glucose can be synthesized to make glucose as oxaloacetate is converted to malate to get it into the cytosol for gluconeogenesis.

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12
Q

Why do patients with type 1 diabetes synthesise ketones?

A

The body continues to produce ketones as in type 1 diabetes not enough insulin is produced. This means glycolysis is inhibited and so pyruvate levels is low. Gluconeogenesis is not inhibited as the body is trying to make blood glucose as there is not the signal to tell the body we have sufficient glucose. Oxaloacetate is converted to malate to be transported out of the mitochondria for gluconeogenesis. This means that oxaloacetate levels drop and cannot be replenished by pyruvate as glycolysis is not working quickly. In the absence of insulin, the body switches over to using stored fat. Fatty acids are mobilised from adipose tissue. This means we then have lots of acetyl-CoA. High Acetyl-CoA but not a lot of oxaloacetate to react with it. It then builds up and so the body uses it to synthesis ketones.

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13
Q

What makes up the electron transport chain?

A

The transport chain has 4 major complexes: I, II, III and IV. There is another electron carrier Ubiquinone and Cytochrome C. Cytochrome C is found highly in the intermembrane space. F0F1ATPase synthesises ATP synthesis.

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14
Q

Give details of oxidative phosphorylation.

A

Electrons from FADH2 and NADH enter at different points. NADH enters at complex I and FADH2 enters at complex II. Complex II, unlike I, III and IV does not transverse the whole membrane. Electrons from FADH2 and NADH then move from one complex to another. When the electrons reach complex IV, they are donated to oxygen, reducing it to oxygen removing it from the chain. As the electrons are transferred from one protein to another, they lose energy. These are high energy electrons and lose energy and drop back into the ground state. Complex I there is a significant drop in free energy between the electrons as they leave NADH and arrive at Coenzyme Q. At complex III, from cytochrome C to B. the energy is retained in the complexes and used to pump hydrogen ions from the mitochondrial matrix into the inner membrane space.

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15
Q

What is the difference between oxidation of NADH & FADH2?

A

FADH2 enters at complex II whereas NADH enters at complex I. For NADH, for each pair of electrons 10 protons are pumped across the membrane. This is very well insulated and so builds up a significant charge gradient across the membrane. The protons provide the energy to synthesise ATP. They flow back through ATPase - for every 3 protons that flows back through ATPase, one molecule of ATP is produced.

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16
Q

How is NADH transported to the electron transport chain from the cytosol?

A

Electrons are transferred from NADH in the cytosol to oxaloacetate, forming malate, which traverses the inner mitochondrial membrane and is then reoxidized by NAD+ in the matrix to form NADH in a reaction catalyzed by the citric acid cycle enzyme malate dehydrogenase.

17
Q

What happen if the electron transport chain is not working?

A

If the electron transport chain is not working, the lack of reduced substrates or more commonly lack of oxygen - there is no proton gradient to drive ATPase enzyme.

18
Q

What happens if ATP synthesis is blocked?

A

If ATP synthesis is blocked, the proton gradient builds up across the inner mitochondrial membrane to the point the complexes do not have enough energy to pump more protons across the membrane as there is now a very high gradient. Energy cannot be released from electron carriers so they cannot so they cant accept any more electrons. The transport chain stops.

19
Q

What are uncouplers? Give an example.

A

Uncouplers are weak acids which are soluble in the membrane. One example is 2,4-dinitrophenol. It is lipid soluble. It can diffuse into the membranes - as it moves from one leaflet to another, when it reaches the inter-membrane space, there are a lot of protons. The protons will be taken on board. To the other side of the membrane where the concentration is much less, it releases the proton. This therefore makes the membrane essentially leaky to protons. They have another way of getting back from the inter-membrane space to the matrix without going through the ATPase channel. This means that oxidation can occur without phosphorylation.