the citric acid cycle and oxidative phosphorylation Flashcards
what main product does glycolysis end with
2 pyruvates
where is pyruvate transported to after glycolysis and under what condition
under aerobic condition
from the cytosol into the mitochondrial matrix
what complex is responsible for pyruvates conversion to CO2 and the acetyl group of acetyl-CoA
Pyruvate dehydrogenase complex
what is pyruvate dehydrogenase complex a complex of
3 enzymes:
E1 – Pyruvate dehydrogenase (acetyl transferring)
E2 – Dihydrolipoyl transacetylase
E3 – Dihydrolipoyl dehydrogenase
what are 2 additional enzymes that are involved in these reactions, but are not part of the complex
- Pyruvate dehydrogenase phosphatase (PDP)
and - Pyruvate dehydrogenase kinase (PDK)
1- Pyruvate dehydrogenase kinase (PDK):
Phosphorylates pyruvate dehydrogenase (E1) using ATP at 3 possible sites (site 1 being the most important)
- 4 isoenzymes; PDK1, 2, 3, and 4
- Site 1: PDK2 > PDK4 ≈ PDK1 > PDK3
- Site 2: PDK3 > PDK4 > PDK2 > PDK1
- Site 3: Only PDK1 can phosphorylate
2- Pyruvate dehydrogenase phosphatase (PDP)
Reverses the effects of pyruvate dehydrogenase kinase.
- Thus, E1 is the rate-determining step
- The ratios of products and substrates of this reaction are important for regulation
describe what the citric acid cycle is
The citric acid cycle is the final common pathway for the oxidation of fuel molecules:
- Carbohydrates
- Fats
- Proteins
Carbohydrates, fatty acids and some amino acids enter the citric acid cycle as what
acetyl coenzyme A (acetyl CoA)
what is the citric acid cycle also know as
Citrate cycle
Krebs cycle
Tricarboxylic acid (TCA) cycle
anaerobic glycolysis extracts what
only a small amount of ATP available from Glucose
Most of the ATP is generated in metabolism generated by the aerobic processing of Glucose
what does the citric acid cycle start with and where abouts doe sit take place
with the complete oxidation of glucose derivatives to carbon dioxide in a sequence of reactions
This all takes place (in eukaryotes) in the mitochondrial matrix
what is acetyl-CoA
Acetyl CoA, an ‘activated’ acetyl (C2) unit (on a coenzyme) is completely oxidised to CO2 and H2O by the citric acid cycle.
explain what must happen in order for oxidation of Acetyl-CoA to take place
reduction must happen to something else
Many ATP molecules can be made from reduced cofactors such as NADH and FADH2 in the electron transport chain via oxidative phosphorylation.
- NADH = Nicotinamide adenine dinucleotide (reduced)
- FADH2 = Flavin adenine dinucleotide (reduced)
explain reaction 1 - citrate synthase
This is a condensation reaction as water is broken down
Condensation of acetyl-CoA with oxaloacetate to form a C4 molecule - citrate.
Reaction is catalysed by citrate synthase, an allosteric enzyme that is inhibited by NADH, ATP, and succinyl-CoA.
explain reaction 2 - aconitase
Citrate is isomerized
The enzyme is called Aconitase because the presumed intermediate is cis-aconitate
explain reaction 3 - isocitrate dehydrogenase
The first of 4 oxidation-reduction reactions
Isocitrate is oxidised, and there is a reduction of NAD+ with loss of a carbon atom as CO2
Isocitrate
dehydrogenase is an allosteric enzyme, which is inhibited by ATP and NADH, and activated by ADP and NAD+
explain reaction 4 - alpha-ketoglutarate dehydrogenase complex
The second oxidation-reduction reaction
α-ketoglutarate dehydrogenase - another multi-enzyme complex
explain reaction 5 - Succinyl-CoA Synthase
Succinyl-CoA cleavage of its bond is linked to the phosphorylation of GDP (guanosine diphosphate)
The GTP that is produced can be used to make an additional ATP by phosphoryl transfer with ADP
- This is NOT a citric acid cycle step. Its adjacent with the cycle
describe Succinyl-CoA
is a Thioester, these are energy rich, and cleavage of this bond is linked to the phosphorylation of GDP (guanosine diphosphate)
explain reaction 6 - succinate dehydrogenase
The third oxidation-reduction reaction of the citric acid cycle.
Succinate is oxidised to fumarate and FAD is reduced to FADH2
explain reaction 7 - fumarase
A condensation reaction to produce malate
explain reaction 8 - malate dehydrogenase
The final oxidation-reduction reaction of the citric acid cycle
- Malate oxidised to Oxaloacetate
- NAD+ reduced to NADH
Oxaloacetate can re-enter into reaction 1 of the cycle
Only 2 ATP is made here
give a quick summary of the citric acid cycle
2x: (Occurs twice as 2 pyruvates)
Acetyl-CoA —> Citrate
Citrate —> Isocitrate (OH + H rearrangement)
Isocitrate —> α-Ketoglutarate
α-Ketoglutarate —-> Succinyl-CoA
Succinyl-CoA —————–>Succinate —-> ATP
Succinate –> Fumarate
Fumarate —> Malate
Malate —-> Oxaloacetate
explain the 3 points of control of the citric acid cycle
1 - Citrate synthase
- Inhibited by ATP, NADH, and succinyl CoA
- Product inhibition by citrate
2 - Isocitrate dehydrogenase
- Activated by ADP and NAD+
- Inhibited by ATP and NADH
3 - α-ketoglutarate dehydrogenase complex
- Activated by ADP and NAD+
- Inhibited by ATP and NADH
- Product inhibition by Succinyl CoA
If inhibited by ATP its activated by ADP, same with NADH and NAD
There is one control point outside the cycle
Pyruvate dehydrogenase
what do control points do
help stop the process running all the time
what are the products of the citric acid cycle
The metabolism of Pyruvate has produced:
- 3 NADH + H+
- 1 FADH2
what happens to the reduced components of the citric acid cycle
take part in Oxidative Phosphorylation within the mitochondria:
- Electron Transport Chain
- Chemiosmosis
explain The Electron Transport Chain and Chemiosmosis
A series of membrane bound proteins which electrons pass through in a series of redox reactions, creating energy
This energy is either given off as heat or used to drive a series of proton pumps to produce a concentration gradient between the mitochondrial matrix and the intermembrane space
All ATP needed to survive is coming from here
explain complex 1 of the electron transport chain
Ubiquinone Oxidoreductase
- NADH dehydrogenase
- Flavin mononucleotide
- 8 iron-sulphur (Fe-S) clusters – these accept electrons and stransfer then to one another
NADH oxidised by this complex
- 2 electrons transferred FMN, then to Fe-S, then to Coenzyme-Q
- This energy pumps 4 protons to the intermembrane space
explain complex 2 of the electron transport chain
Succinate dehydrogenase
2nd entry point into the electron transport chain
- FADH2 oxidised to FAD and H+, with the electrons moved through a series of Fe-S clusters to CoQ as in Complex 1
- No protons pumped through this entry point
(Same as complex 1 but for FADH2 instead)
explain coenzyme Q in terms of the electron transport chain
Electron carrier – taking electrons from complex 1 and 2 to complex 3
Transfers electrons to Complex 3 through the Q Cycle
what is coenzyme Q also known as and whats its structure
Also known as Ubiquinone
Quinone with a hydrophobic tail
explain complex 3 of the electron transport chain
Cytochrome c reductase:
- Cytochrome b
- Cytochrome c
- Rieske subunits (contains Fe-S clusters)
Cytochrome
Is a Heme containing electron transport protein, so Alternate between Fe2+ and Fe3+ states ( as heme = iron)
- Can only transport 1 electron at a time using the Q cycle
Releases 4 proton into the intermembrane space, ( Now a total of 8 protons released into intermembrane space)
explain the Q cycle in complex 3
2 steps:
Cycle 1:
Ubiquinol (CoQH2) binds to site 1 and donates 2 electrons that go into 2 separate pathways
- 1 goes to the Fe-S clusters, and then on to cytochrome c, which is reduced
- 1 goes to cytochrome b, and then on to CoQ bound at the second site, which becomes the CoQH- radical
This pumps 2 H+ into the intermembrane space
Cycle 2:
A repeat of cycle 1
- The electron donated to cytochrome b stabilises the CoQH- radical to CoQH2
Another 2 H+ ions pumped out
explain complex 4 of the electron transport chain
Cytochrome c oxidase:
- Cytochrome a
- Cytochrome a3
- Heme and Copper groups
Oxidises cytochrome c, transferring 2 electrons to Oxygen
- Which becomes water
2 protons pumped into the intermembrane space
explain complex 5 of the electron transport chain
ATP Synthase, formed of :
- F0
Forms a rotor mechanism that is constantly protonated and deprotonated - F1
As F0 rotes it changes the orientation and conformation of F1, catalysing the formation of ATP from ADP
Every 4 H+ = 1 ATP produced
(For every 1 glucose molecule about 30 ATP are roughly produced)
