PFK-1 is a major point for the regulation of glycolysis (ATP and citrate from TCA cycle are inhibitors of PFK-1, while ADP, AMP, and F-2,6-P are activators (ie when ATP, the main goal of glycolysis is high, there is no need to make more, so this is a good place to stop the production)
ΔG'0 = -14.2kJ/mol
4th step of glycolysis:
What happens to the fructose 1,6-biphosphate?
Cleavage of 6-carbon sugar phosphate to 2 3-carbon sugar phosphates
Catalyzed by aldolase
Thermodynamically unfavorable, driven by rapid removal of G-3-P
Yields 2 different triosephosphates (glyceraldehyde 3-phosphate (G-3-P, aldose) and dihydroxyacetone phosphate (DHAP, ketose))
ΔG'0 = 23.8kJ/mol
5th step of glycolysis:
What happens to the 2 triosephosphates?
Only the glyceraldehyde 3-phosphate can be directly degraded, so the dihydroxyacetone phosphate is rapidly and reversibly converted to glyceraldehyde 3-phosphate which is catalyzed by triosephosphate isomerase (TIM).
Driven by coupling this process to other glycolytic reactions which have a large negative ΔG'0.
ΔG'0 = 7.5kJ/mol
6th step of glycolysis:
What happens to the glyceraldehyde 3-phosphate?
Glyceraldehyde 3-phosphate is oxidized and phosphorylated
Pyruvate, which is made in the cytosol, enters the mitochondria and is decarboxylated and coupled to Coenzyme A (Co-A) and produces one NADH molecule
This is catalyzed by pyruvate dehydrogenase complex
ΔG'0 = -33.4kJ/mol
How is the TCA cycle regulated?
1. Citrate synthase (inhibited by succinyl-CoA, citrate, ATP, and NADH, where ATP and NADH levels determine energy status of the cell)
-In resting cells: NADH/NAD+ and ATP/ADP ratios are high
2. Isocitrate dehydrogenase (inhibited by high levels of ATP and NADH, activated by high levels of ADP and NAD+)
3. α ketoglutarate dehydrogenase (inhibited by high levels of NADH and succinyl-CoA, activated by high levels of AMP)
What is ETC?
The Electron Transport Chain
Is aerobic or anaerobic respiration more efficient?
Oxidation of glucose or fatty acids provides much more energy than what?
Oxygen serves as the terminal acceptor for what?
Electrons carried by NADH and FADH2
Oxygen is reactive and makes what?
Toxic intermediates (cell evolved detoxification enzymes like catalase, superoxide dismutase)
What are 3 properties of oxygen that favor energy extraction?
It is abundant (~21% of air)
It diffuses through membranes
It is very reactive and easily accepts electrons
Where is ETC organized as a chain?
On the inner mitochondrial membrane
What is a quick summary of ETC?
High energy electrons extracted for carbon sources (glucose, fatty acid) on NADH and FADH2 are transported to oxygen via the transportation down an electron chain. Chemical energy is generated in the process.
What does electron transfer down the ETC decrease?
The reduction potential (ΔE'0)
What is the ΔE'0 for transfer of electrons from NADH to oxygen?
ETC consists of how many complexes located on the inner mitochondrial membrane?
What is Complex I for ETC?
What is Complex II for ETC?
What is Complex III for ETC?
Cytochrome b1 complex
What is Complex IV for ETC?
What are key components used to carry electrons through the ETC chain?
quinones, iron-sulfur proteins, cytochromes
What are quinones?
Anchored to inner mitochondrial membrane (via the isoprenoid tail which (n~10))
Mobile inside the membrane
Thought to sit on the hydrophobic core
Quinones accept electrons from what?
NADH and FADH2
How do quinones carry electrons?
The 2-step reduction allows quinones to carry electrons one of 2 ways:
-Either 2 electrons as dihydroquinone
-Or 1 electron as semiquinone
What are iron-sulfur proteins?
Also called iron-sulfur centers (FeS)
Contain 2, 3, 4, or 8 iron atoms bound to a protein via chelation with cysteine residues
Sulfur also forms a bride between irons
4-Fe centers have a tetrahedral structure resembling a cube
Iron-sulfur centers transfer how many electrons at one time?
How do iron-sulfur clusters transfer electrons?
Transfer is coupled to the red-ox reaction (Iron-sulfur clusters under red-ox without binding protons)
What is the equation for the red-ox reaction associated with iron-sulfur centers?
2Fe3+ + 1e- <---> Fe3+ + Fe2+
How do cytochromes transfer electrons?
Involves a heme group (a prosthetic group that contains iron that it chelated by 4 nitrogen groups)
The heme groups in the 3 cytochromes (a, b, & c) differ by the types of substituents attached to the porphyrin ring
Cytochromes transfer 1 electron using the single iron center
Which of the 3 cytochrome's heme group is covalently attached to the protein backbone via cysteine residues?
What is the equation associated with the transfer of electrons in cytochromes?
Fe3+ + 1e- <---> Fe2+
What is Complex I in ETC?
What is the mitochondrial location of Complex I (NADH Dehydrogenase)?
How many subunits does Complex I (NADH Dehydrogenase) have?
What are the prosthetic groups of Complex I (NADH Dehydrogenase)?
7 Fe-S clusters
What is Complex II in ETC?
What is the mitochondrial location of Complex II (Succinate Dehydrogenase)?
How many subunits does Complex II (Succinate Dehydrogenase) have?
What are the prosthetic groups of Complex II (Succinate Dehydrogenase)?
What is Complex III in ETC?
Cytochrome b1 Complex
What is the mitochondrial location of Complex III (Cytochrome b1 Complex)?
How many subunits does Complex III (Cytochrome b1 Complex) have?
What are the prosthetic groups of Complex III (Cytochrome b1 Complex)?
Cyt b sub H
Cyt b sub L
Cyt c sub 1
1 Fe-S cluster
What is Complex IV in ETC?
What is the mitochondrial location of Complex IV (Cytochrome oxidase)?
How many subunits does Complex IV (Cytochrome oxidase) have?
What are the prosthetic groups of Complex IV (Cytochrome oxidase)?
Heme A sub 3
What does energy recovery from electrons carried by NADH depend on?
Complexes I, III, & IV
How do electrons pass from one complex to another?
Using the Q cycle and soluble cytochrome c proteins
Describe the movement of electrons in Electron Transport Complex I
1. Electrons from NADH go to FMN forming FMNH2
2. Those go to 2 Fe-S clusters, one electron at a time
3. Those go to UQ (coenzyme Q)
The electron movement from NADH to UQ causes movement of H+ into the intermembrane space (Unknown mechanism)
What is the equation for the movement of electrons in Electron Transport Complex I?