The Pyruvate Dehydrogenase Complex and the TCA cycle. Flashcards
What are co-enzymes?
Small organic molecules that will help an enzyme perform its job. Co-enzymes are often derived from vitamins.
What are kinases?
These enzymes will add phosphate groups to proteins.
What amino acid residues get phosphorylated?
Serine.
Threonine.
Tyrosine residues.
What are phosphatases?
These enzymes will remove phosphate groups from proteins.
What is the final product of glycolysis?
2 Pyruvate molecules.
How many carbons does each pyruvate molecule have?
3.
What happens when pyruvate is oxidised further?
All of the electrons are removed to form CO2 and water.
Is the breakdown of pyruvate catabolic or anabolic?
Catabolic.
What are the goals of the PDH cycle and the ETC?
To get energy out of pyruvate.
Where are the 2 molecules of pyruvate formed?
In the cytoplasm.
Where are the enzymes for the TCA cycle and the PDH cycle found?
In the mitochondria.
What are the main energy producers in the cell?
The mitochondria.
Describe the interior of the mitochondria?
The interior of a mitochondrion is made up of 2 layers or membranes that are separated by a space.
What are the 2 membranes in the mitochondria called?
The outer and inner membrane.
What is the space between the outer an inner membrane called?
The inter-membranous space.
Why is the inner mitochondrial membrane invaginated?
To increase surface area.
Is the inner mitochondrial membrane easy for molecules to penetrate?
No.
It is highly impermeable.
Where in the mitochondria does the TCA cycle and PDH step occur?
In the mitochondrial matrix.
Where is the mitochondrial matrix located?
On the inside of the inner mitochondrial membrane.
What metabolic functions occur in the outer membrane of the mitochondria?
Phospholipid synthesis.
Fatty acid de-saturation.
Fatty acid elongation.
What metabolic functions occur in the inner membrane of the mitochondria?
Electron transport.
Oxidative phosphorylation.
Metabolite transport.
What metabolic functions occur in the inter membranous space of the mitochondria?
Nucleotide phosphorylation
What metabolic functions occur in the mitochondrial matrix of the mitochondria?
TCA cycle.
Pyruvate oxidation.
DNA replication.
Beta oxidation of fats.
Protein synthesis.
RNA synthesis.
Does the PDH step or the TCA cycle occur first?
The pyruvate molecules enter the PDH complex first then go into the TCA cycle.
What is formed in the PDH complex?
Pyruvate is oxidised to ACoA.
How many carbons does ACoA have?
2.
Are the any by products of the oxidation of pyruvate to ACoA in the PDH step?
The carbon that is removed from pyruvate is lost as CO2.
The energy from the oxidation forms an NADH.
What molecule enters the TCA cycle?
ACoA.
Can the formation of ACoA from pyruvate be reversed?
No.
The reaction is irreversible.
Is the PDH complex a single enzyme or multiple enzymes?
A single enzyme.
Where is the PDH complex found?
In the mitochondrial matrix.
How many enzymes does the PDH complex contain?
3.
How many regulatory proteins does the PDH complex contain?
2.
How many coenzymes does the PDH complex require so that it can function?
5.
What are the 3 enzymes or catalytic proteins in the PDH complex?
Pyruvate dehydrogenase.
Dihydrolipoyl dehydrogenase.
Dihydrolipoyl transacetylase.
What are the 2 regulatory proteins in the PDH complex?
Protein kinase (PDH kinase).
Protein phosphatase (PDH phosphatase).
What are the 5 coenzymes required by the PDH complex?
NAD+.
FAD.
Thiamine pyrophosphate (TPP).
Lipoic acid.
CoASH (co-enzyme A).
Nobody.
Fucks.
The.
Large.
Chicks.
What happens if a coenzyme is missing from the PDH complex?
Then the PDH complex cannot function.
Which coenzymes are vitamins?
NAD+.
FAD.
Thiamine pyrophosphate (TPP).
CoASH (co-enzyme A).
Which coenzyme is not a vitamin?
Lipoic acid.
How are the co-enzymes that are vitamins in the PDH complex acquired?
From the diet.
What enzymes in the PDH complex are involved in the conversion of pyruvate to ACoA?
All 3 of them.
Which co-enzymes will carry the acetyl group through the complex and to give it to CoA and form ACoA?
Co-ASH and TPP.
Which co-enzymes will transfer electrons from substances that have been oxidised to eventually form NADH.
Lipoic acid, NAD+ and FAD
What will be the output of 1 pyruvate molecule in the PDH complex?
1 ACoA, 1 Pyruvate and 1 CO2.
What will be the output of 1 glucose molecule in the PDH complex?
2 ACoA, 2 Pyruvate and 2 CO2.
When will the PDH complex be active?
When it is de-phosphorylated.
What will de-phosphorylate the PDH complex?
The regulatory enzyme, PDH phosphatase.
What stimulates the de-phosphorylation of the PDH complex by PDH phosphatase?
High levels of insulin in the liver.
High levels of calcium or magnesium in skeletal muscle.
When will the PDH complex not be active?
When it is phosphorylated.
What will phosphorylate the PDH complex?
The regulatory enzyme, PDH kinase.
What will activate PDH kinase?
ATP.
ACoA.
NADH.
Other than the PDH complex, what other methods can be used to create ACoA?
Triglycerides to ACoA.
Protein to ACoA.
Glycogen to ACoA.
How does glycogen for ACoA?
It can be broken down by glycogenolysis to form glucose.
Glucose can then form pyruvate.
What are triglycerides?
Fats which are a form of stored energy.
How can triglycerides form ACoA?
Triglycerides are broken down to glycerol and free fatty acids by lipolysis.
Free fatty acids are then broken down via beta oxidation to form ACoA.
How can proteins be used to form ACoA?
Via proteolysis which breaks them down to amino acids.
The amino acids can be broken down by oxidative de-amination to ACoA.
What other names can the TCA cycle be referred to as?
The tricarboxylic acid cycle (TCA cycle).
The krebs cycle.
The citrate cycle.
Where does the TCA cycle occur?
In the mitochondrial matrix.
What happens in the 1st step of the TCA cycle?
ACoA is added to oxaloacetate which creates a molecule called citrate.
How many carbons does oxaloacetate have?
4.
How many carbons does citrate have?
6.
How many steps are in the TCA cycle?
8.
What is the final product of the TCA cycle?
Citrate allowing the whole cycle to repeat itself.
How many carbons are lost from citrate in the TCA cycle?
2.
How much energy is generated by the TCA cycle per ACoA?
3 NADH = 9 ATP.
1 GTP = 1 ATP.
1 FADH2 = 2 ATP.
Total = 12 ATP.
How much energy is generated by the TCA cycle per glucose molecule?
6 NADH = 12 ATP.
2 GTP = 2 ATP.
2 FADH2 = 4 ATP.
Total = 24 ATP.
How many times does the TCA cycle turn per glucose molecule?
2.
What happens at step 1 of the TCA cycle?
Acetyl CoA combines with oxaloacetate to form citrate.
A water molecule will then remove CoA.
What enzyme is involved in step 1 of the TCA cycle?
Citrate synthase.
What happens at step 2 of the TCA cycle?
An isomerisation reaction takes place and an isocitrate is formed.
What happens in the isomerisation of citrate in step 2 of the TCA cycle?
An OH is moved from carbon 3 to carbon 4.
The acetyl group is lost as CO2.
What enzyme is involved in step 2 of the TCA cycle?
Acontinase.
What happens at step 3 of the TCA cycle?
Isocitrate is de-carboxylated and the 1st CO2 molecule is removed to form alpha-ketogluterate.
How many carbons does alpha-ketogluterate have?
5.
Is any energy produced in step 3 of the TCA cycle?
1 NADH.
What happens at step 4 of the TCA cycle?
α-ketogluterate loses a CO2 molecule and COA is added in its place.
This forms succinyl CoA and NADH.
AKDH is similar to pyruvate dehydrogenase as it requires the same 5 coenzymes.
How many carbons does succinyl CoA have?
4 carbons bound to CoA.
What enzyme is used in step 4 of the TCA cycle?
Alpha-ketoglutarate dehydrogenase.
Is any energy produced in step 4 of the TCA cycle?
1 NADH.
What happens at step 5 of the TCA cycle?
The high energy bond between succinyl and CoA is broken to form succinate.
Is any energy produced in step 5 of the TCA cycle?
1 GTP.
What enzyme is used in step 5 of the TCA cycle?
Succinyl CoA synthetase (succinate thiokinase).
What happens at step 6 of the TCA cycle?
2H atoms are oxidised and removed from succinate to form fumarate.
When succinate is converted to fumarate by succinate dehydrogenase, what will replace the 2 H atoms that are lost from succinate?
A double bond is formed within succinate to compensate for the loss of the 2 H atoms
What enzyme is used in step 6 of the TCA cycle?
Succinate dehydrogenase.
Is any energy produced in step 6 of the TCA cycle?
1 FADH2.
What happens at step 7 of the TCA cycle?
A water molecule is added to fumarate by a hydrolase to create L-malate.
How does fumarase change fumarate to malate?
It adds an OH and an H to carbons on either side of the double bond.
This removes the double bond that was formed in the previous step.
What enzyme is used in step 7 of the TCA cycle?
Fumarase.
What happens at step 8 of the TCA cycle?
L-malate is oxidised to oxaloacetate.
Is any energy produced in step 8 of the TCA cycle?
1 NADH.
What enzyme is used in step 8 of the TCA cycle?
Malate dehydrogenase.
What happens to the oxaloacetate that is formed is step 8 of the TCA cycle?
It is re-entered into the TCA cycle.
What steps of the TCA cycle produce energy?
Step 3.
Step 4.
Step 5.
Step 6.
Step 8.
What is produced by the isocitrate dehydrogenase step in the TCA cycle?
1 NADH.
1 CO2.
What is produced by the alpha keto-gluterate de-hydrogenase step in the TCA cycle?
1 NADH.
1 CO2.
What is produced by the succinyl CoA synthase step in the TCA cycle?
1 GTP.
What is produced by the succinate dehydrogenase step in the TCA cycle?
1 FADH2.
What is produced by the malate dehydrogenase step in the TCA cycle?
1 NADH.
How much ATP is generated by 1 turn of the TCA cycle?
12 ATP.
What are the 4 regulated enzymes in the TCA cycle?
Citrate synthase.
Isocitrate dehydrogenase.
Alpha KG dehydrogenase.
Succinate dehydrogenase.
In general, what kind of molecules will regulate the enzymes in the TCA cycle?
High energy molecules.
NADH.
ATP.
What is citrate synthase activated by?
Substrate availability.
ADP.
Calcium.
What is citrate synthase regulated by?
Fatty acyl CoA.
ATP.
NADH.
Succinly CoA.
What is isocitrate dehydrogenase activated by?
Calcium.
ADP.
What is isocitrate dehydrogenase regulated by?
ATP.
NADH.
What is alpha-KG dehydrogenase activated by?
Calcium.
What is alpha-KG dehydrogenase regulated by?
ATP.
GTP.
NADH.
Succinly CoA.
What is succinate dehydrogenase activated by?
ADP.
Succinate.
Phosphate.
What is succinate dehydrogenase regulated by?
Oxaloacetate.
What can citrate inhibit in glycolysis?
PFK-1 in step 3.
Citrate can be used as a pre-cursor for what?
Fatty acid and sterol synthesis.
How much ATP is produced via the aerobic respiration of 1 glucose molecule?
36-38 molecules of ATP produced per glucose molecule.
What can influence the final amount of ATP that is generated by aerobic respiration?
The use of different shuttles will determine whether 36 or 38 ATPs are generated.
How much CO2 is generated by glycolysis?
0.
How much CO2 is generated in the PDH complex?
0.
How much CO2 is generated in the TCA cycle?
1 turn = 2.
2 turns = 4.
How much NADH is generated by glycolysis?
2.
How much NADH is generated in the PDH complex?
2.
How much NADH is generated in the TCA cycle?
6 = 2 turns.
3 = 1 turn.
1 NADH gives how much ATP?
3 ATPs.
How much ATP is generated by NADH production in glycolysis?
6.
How much ATP is generated by NADH production in PDH complex?
6.
How much ATP is generated by NADH production in the TCA cycle?
9 = 1 turn.
18 = 2 turns.
How much FADH2 is generated by glycolysis?
0.
How much FADH2 is generated in the PDH complex?
0.
How much FADH2 is generated in the TCA cycle?
1 = 1 turn.
2 = 2 turns.
FADH2 is worth how many ATPs?
2 ATPs.
How much ATP is generated by FADH2 production in the TCA cycle?
1 turn = 2 ATP.
2 turns = 4 ATP.
How much GTP is generated by glycolysis?
0.
How much GTP is generated in the PDH complex?
0.
How much GTP is generated in the TCA cycle?
1 = 1 turn.
2 = 2 turns.
GTP is worth how many ATPs?
1.
How much ATP is generated by substrate level phosphorylation in glycolysis?
2.
How much ATP is generated by substrate level phosphorylation in the PDH complex?
0.
How much ATP is generated by substrate level phosphorylation in the TCA cycle?
1 turn = 1.
2 turns = 2.
What is the maximum ATP yield of glycolysis?
8 ATP.
What is the maximum ATP yield of the PDH complex?
6 ATP.
What is the maximum ATP yield of the TCA cycle?
24 ATP.
What are the clinical features of a PDH deficiency?
Lactic acidosis.
Neurological defects.
Myopathy.
Death.
How will an inherited deficiency in the PDH complex cause lactic acidosis?
Pyruvate cannot be converted to ACoA and will result in a build up of pyruvate molecules in the mitochondria.
The body converts pyruvate to lactate and alanine.
This will cause lactic acidosis.
What is the major problem with a PDH deficiency?
If pyruvate cannot be converted to lactate then the body is missing out on most of its energy.
Is a PDH deficiency usually fatal?
Yes.
How will a thiamine deficiency affect ATP output?
It will decrease it.
What are the clinical features of a thiamine deficiency?
Ataxia.
Ophthalmolplagia.
Memory loss.
Cerebral haemorrhage.
Where is the vitamin thiamine used?
In the PDH complex.
What is the most common co-enzyme deficiency in the PDH complex?
Thiamine.
What is another name for a thiamine deficiency?
Werneke-Korsakoff syndrome.
What kind of people are most likely to have a thiamine deficiency?
Alcoholics and malnourished individuals.
Is thiamine used as a co-enzyme in any other enzymes?
Thiamine is also required for alpha-KG which is used in the TCA cycle.
