Mitochondrial Synthesis of ATP Flashcards
What are daily energy needs like of a healthy 70 kg male?
- daily energy needs are around 12 MJ
- blood glucose and glycogen make up near a third of daily energy needs
- there is 400 MJ of triglyceride and 100 MJ of usable protein available
What is meant by “useable protein”?
Protein that could be used without endangering our lives
The loss of muscle protein is never desirable and is the last resort
What is the concentration of ATP in cells?
It is present at a relatively high concentration
This is around 6 mM
What is daily ATP turnover?
How much ATP is found in the average human body?
An average human body contains around 75 g of ATP
ATP turnover is 75 kg/day
How much energy from food is converted into useful energy?
Half the energy from food is converted to ATP
Half of this energy is converted to useful work
25% of energy from food is turned into useful work
What is the composition of the outer mitochondrial membrane?
How permeable is it?
What gradients are present?
Outer membrane is smooth
It is freely permeable to molecules under 5000 Da (including ions)
There are NO ionic or electrical gradients
What are cristae?
Why are they necessary?
The inner mitochondrial membrane is folded into cristae
They protrude into the mitochondrial matrix to increase the surface area for the proteins of electron transport
How permeable is the inner mitochondrial membrane?
It is permeable only to a small number of molecules via specific transporters
What gradients are present across the IMM?
it is a good electrical insulator and is capable of maintaining large ionic and electrical gradients
What is the role of cardiolipin within the IMM?
It is a phospholipid that is capable of maintaining large ionic gradients across the IMM
How does the amount of protein in the IMM compare to the amount of lipid?
The IMM contains more protein than lipid
e.g. respiratory enzymes, transporter proteins etc.
What substances are located within the mitochondrial matrix?
- wide range of enzymes
- high concentrations of substrates, cofactors and ions
- mitochondrial DNA, RNA and ribosomes
What is found within the intermembrane space?
What are metabolite and ion concentrations like?
Cytochrome C is found in the intermembrane space
Metabolite and ion concentrations are similar to in the cytosol
What happens to pyruvate at the end of glycolysis?
It is transported across the inner mitochondrial membrane
It moves from the cytosol into the matrix
What is the main reaction of the link reaction?
Pyruvate dehydrogenase catalyse the conversion of pyruvate to acetyl CoA
What is the most important cofactor of pyruvate dehydrogenase?
Thiamine pyrophosphate (TPP)
Thiamine is a B vitamin that is important in maintaining metabolism
What does a lack of thiamine cause?
Disruption to the function of pyruvate dehydrogenase
This causes Beri-Beri that has neurological and cardiovascular symptoms
What can cause Wernicke-Korsakoff syndrome?
A lack of thiamine seen in alcohol dependency
Alcohol affects the absorption of thiamine in the gut
Wernicke-Korsakoff syndrome affects neurological function
Why is pyruvate dehydrogenase called a “key decision point” in metabolism?
- acetyl CoA cannot be converted back into glucose
2. conversion of pyruvate to acetyl CoA commits the C atoms of glucose to energy production of lipid synthesis
When is pyruvate dehydrogenase inhibited?
When energy levels are high, phosphorylation is promoted
e.g. high levels of acetyl CoA, NADH or ATP
What are the 2 enzymes involved in controlling pyruvate dehydrogenase through phosphorylation?
Pyruvate dehydrogenase kinase phosphorylates PDH to inactivate it
Pyruvate dehydrogenase phosphatase will remove the phosphate from PDH to reactivate it
What happens if there is a sudden energy demand in a cell?
This leads to an increase in free Ca2+ ions
Increase in free Ca2+ leads to the removal of the phosphate group and activation of pyruvate dehydrogenase
Where may the acetyl CoA entering the Krebs cycle be derived from?
- acetate (alcohol breakdown)
- pyruvate (glucose)
- fatty acids
- ketone bodies
- amino acids
What is the first of the 2 stages involved in the Krebs cycle?
- synthesis of citrate (6C) which then loses 2C as CO2 to become succinyl CoA (4C)
oxaloacetate reacts with acetyl CoA to produce citrate
What is the second of the 2 stages involved in the Krebs cycle?
- oxidation of succinyl CoA to regenerate oxaloacetate and initiate another round of the cycle
What are the main outputs of the Krebs cycle?
- the electron carriers, NADH and FADH2
- CO2 - waste product
- 1 GTP (which is equivalent to 1 ATP)
What are NADH and FADH2?
They are reduced coenzymes
They are carriers of hydrogen ions and high energy electrons
What controls the entry of pyruvate into the Krebs cycle?
- the need for energy
2. the availability of acetyl CoA from fat oxidation
What 2 factors are involved in controlling the entry of pyruvate into the Krebs cycle depending on the need for energy?
- ATP:ADP ratio
2. NADH:NAD+ ratio
What is the first point at which the Krebs cycle can be controlled?
What can this stage be inhibited by?
Incorporation of acetyl CoA into the Krebs cycle by citrate synthase
Inhibited by:
- ATP
- NADH
- succinyl-CoA
- citrate
What is the second point at which the Krebs cycle can be controlled?
What can this stage be inhibited and stimulated by?
Conversion of isocitrate into a-ketoglutarate by isocitrate dehydrogenase
Inhibited by ATP and NADH
Stimulated by ADP and NAD+
What is the third point at which the Krebs cycle can be controlled?
What can this stage be inhibited by?
Conversion of a-ketoglutarate to succinyl-CoA by a-ketoglutarate dehydrogenase
Inhibited by:
- ATP
- NADH
- succinyl-CoA
At which stages may amino acid carbon skeletons be fed into the Krebs cycle?
They can be added or removed from the cycle as oxaloacetate and a-ketoglutarate
These molecules are important in amino acid synthesis
What can enter the Krebs cycle as succinyl-CoA?
- odd-chain fatty acids
2. Amino acids - Ile, Met and Val
What can enter the Krebs cycle as fumarate?
- Amino acids - Asp, Phe and Tyr
What are the compounds involved in the Krebs cycle?
- acetyl CoA joins with oxaloacetate to form citrate
- isocitrate
- a-ketoglutarate
- succinyl-CoA
- succinate
- fumarate
- malate
- back to oxaloacetate
Why may citrate be transported from the mitochondria into the cytosol?
It is used to synthesise fatty acids and cholesterol in the cytosol