Biochem Post-midterm Mitochondrial function
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What are some processes that go on in the cytosol? mitochondrial matrix? both compartments?
- Cytosol: glycolysis, pentose phosphate shunt, fatty acid synthesis
- Mitochondrial matrix: citric acid cycle, oxidative phosphorylation, B-oxidation of fatty acids, ketone body formation
- Both compartments: gluconeogenesis, urea synthesis
Balanced reaction of citric acid cycle?
Acetyl-CoA + 3 NAD+ + FAD + GDP + Pi+ 2 H2O->
2 CO2+ 3NADH + FADH2 + GTP + 2H+ + CoA
What are some precursors that can be made from the citric acid cycle?
- A-ketoglutarate -> amino acids
- Succinyl CoA-> porphyruns
- Oxaloacetate-> amino acids and phosphoenol pyruvate (that can make glucose)
- Pyruvate -> Oxaloacetate (using ATP Co2)
How is the citric acid cycle controlled
Any step that requires NAD+ or FAD (4 steps)
- Acetyl-CoA-> Citrate, inhibited by ATP , acetyl CoA, and NADH
- Isocitrate-> a-ketoglutarate, inhibited by ATP, promoted by ADP
- A-ketoglutarate-> Succinyl CoA, inhibited by succinyl CoA and NADH
The mitochondrial respiratory chain converts ___ to ____
What are the names of the complexes in the ETC
- 1= NADH-Q Reductase
- 2= Q (Succinate: Q reductase)
- 3= Cytochrome reductase
- Cytochrome C (transfers an electron between 3 and 4)
- 4= Cytochrome oxidase
What is the endosymbiont hypothesis?
Mitochondria have evolved from aerobic bacteria which were phagocytosed by eukaryote cells at the time oxygen appeared on earth
similarities between mitochondria and bacteria: cardiolipin, transporters, ribosomes, circular DNA+ RNA
Drugs that can inhibit mitochondrial protein synthesis?
Tetracycline and chloroamphenicol (antibiotics)
- extensive use of these drugs can inhibit
- a) bone marrow mitochondrila protein synthesis leading to decreased production of white or red blood cells
- 2. intestinal epithelium cell division.
- Iron sulfur protein
- Q(Ubiquinone) reduced to QH2(Ubiquinol through a semi-quinone intermediate
- Cytochome C Reductase
- Iron sulfur protein bound to a heterodimer (Cyt C and Cyt B)
- QH*-> Q
- Cyt Fe+3 -> Cyt Fe+2
- Located on the inner mitochondrial membrane
- Cytochrome C binds this and Complex 3
- 4H+ + O2 -> 2H2O
- Sends 4 hydrogens across the membrane(from the matrix to the intermembrane space) to establish gradient used by ATP synthase
Poisons that inhibit the ETC
rotenone and amytal= NADHQ Reductase -> QH2
antimycin= Cytochrome B-> Cytochrome C1
(cyanide)CN-, N3-(azide), CO (carbon monoxide) = Cytochrome oxidase-> O2
Cytochrome C- catalytic site
Consists of heme group attached to sulfur above the plan, and nitrogen below the plane (Met80, His18)
Heme group in cytochrome C is covalently attached to 2 cysteine side-chains by thioester linkages (Vinyl group + Cysteine-> Thioester linkage)
What is the dual function of cytochrome C?
- Electron transport for ATP production
- Major cause of most programmed cell death when cytochrome C is released into the cytosol
Properties of Cytochrome C
- 26/104 a.a. have been invariant for 1.5 *10^9 years
- Met 80 and His 18 co-ordinate Fe of the heme
- 11 residues from 70-80 are unchanged/invariant throught all cytocome C's (these residues create a hydrophobic crevice)
- a number of invariant arginine and lysine clusters can b found on the surface of the protein
How does the ETC work?
Pumps protons out of the matrix to establish a gradient, protons will flow down their gradient to generate ATP using ATP synthase
When ADP is readily available, the functioning of the ETC increases
Mitochondrial membrane transporters
- Cytosolic NADH oxidation (allows NADH produced in cytosol to further enhance oxidative phosphorylation)
- Acetyl CoA (NADPH export)(Isocitrate, and Citrate can leave to increase NADPH in cytosol for drug metabolism/fatty acid synthesis)
- Transport systems of mitochondria
- Gluconeogenesis and glucose transport (malate can leave and eventually turn into glucose)
creatine stored in muscles and makes ATP - enhances performance in certain repetitive, high intensity, short-term exercise tasks. Offsets fatigue in mitochondrial myopathy patients and improves the mobility of the elderly
- -an essential electron and proton carrier in the mitochondrial respiratory chain
- -found in all intracellular membranes
- -acts as an antioxidant
- -synthesized in mitochondria- deficiency may occur in patients taking cholesterol lowering drugs
What does pyruvate dehydrogenase do?
- Converts pyruvate to Acetyl-CoA (enters the CAC)
- Nad+ -> NADH
- CoA-SH -> CO2
What do fluorocitrate, fluoroacetyl CoA, and fluoroacetate do?
- Inhibit aconitase, this can cause a buildup in citrate
- Buildup of citrate will cause:
- -complexing with iron
- -lack of shuttling of isocitrate to detoxify drugs
- -lack of ETC/citric acid cycle functioning
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