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27 Cards in this Set
- Front
- Back
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What metabolic reactions take place in the mitochondria?
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-CAC
-PDC -B-oxidation of FA -ETC |
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Describe the mito from outside to inside.
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Outer mito membrane --> Intermembrane space --> Inner mito membrane --> mitochondrial matrix
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What are key features of the OMM?
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Has porins which form large aqueous channels that allow passage of molecules such as NADH, FADH2 and molec with weight < 10,000 g/mol
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What are key features of IMM?
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-80% ptn by weight
-has Cardiolipin which thickens the mb and makes it impermeable to ions -Has transport ptns that are part of ETC (ATP synthase) -Forms cristae which inc SA to maximize ATP production |
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Key features of the mitochondrial matrix?
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Contains:
-PDC -7 of 8 CAC enz -B-oxid of FA -Enz used for oxid of certain aa -enz of low MW, DNA, RNA etc |
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WHat is the evidence for the endosymbyosis theory for mito?
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-Double mb structure (OMM and IMM)
-Circular DNA genome -rRNA=16S -Mito ptn synthesis inhibited by chloramphenicol (which also inhibits bacterial ptn synthesis) but does not inhibit cytoplasmic ptn synthesis |
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How is pyruvate transported into the mito?
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Pyruvate translocase
-Acts as an H+ symport Carries pyruvate and H+ in (even though pyruvate is going against its [gradient]) |
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What is an example of an antiport ptn?
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ATP/ADP exchange ptn
-transmb potential-cyclical process -ATP is more negative than ADP and mito is more negative than cytosol so ATP is expelled to cyto. and ADP is brought into mito |
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What does the ATP synthase do?
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Transports H+ to P ADP to ATP
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What are the 3 subunits of PDC and their functions?
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E1: Pyruvate Dehydrogenase
E2: Dihydrolipoyl Transacetylase E3: Dihydrolipoyl Dehydrogenase |
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What are the accessory ptns in the PDC and their functions?
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-E3 Binding protein: ptn that binds E3 to E2
-Pyruvate deydrogenase Kinase (PDK): P E1, which inactivates it -Pyruvate dehydrogenase Phosphatase (PDP): reverses the effects of PDK on PDC |
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What does the PDC do?
Where does this take place? |
Pyruvate--> Acetyl CoA
Mitochondrial matrix |
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What is Beriberi?
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Thiamine deficiency, unable to convert pyruvate to Acetyl CoA
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What are the cofactors of the PDC and their functions?
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-TPP: bound to E1. Decarboxylates pyruvate to get hydroxyethyl-TPP carbanion
-Lipoic Acid: covalently linked to E2 (lipoamide). Accepts the hydroxyethyl carbanion from TPP as an acetyl gp -Coenzyme A (CoA): Substrate for E2. Accepts acetyl gp from E2 -FAD: bound to E3. Reduced by lipoamide -NAD+: Substrate for E3. Reduced by FADH2 |
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What is the overall rxn of PDC?
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Pyruvate + CoA-SH + NAD+ --> Acetyl CoA + NADH + H+ + CO2
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What is step 1 of PDC?
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-Covalent catalysis btw E1, E2 and substrate
-Nuc attack on pyruvate -Decarboxylation facilitated by TPP |
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What is step 2 of PDC?
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-Hydroxyethyl-TPP makes carbanion which does a nuc attack on lipoamide of E2
-Transfer a 2C gp from E1 to E2 and oxidizes a C to a COOH -Prod: acetyl-dihydrolipoamide (has a thioester linkage, high E) |
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What is step 3 of PDC?
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-Transesterification catalyzed by E2
-get Acetyl CoA |
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What is step 4 of PDC?
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-Disulfide exchange
-E3 oxidizes E2's sulfhydryl gps to regenerate the lipoamides diS gp |
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What is step 5 of PDC?
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-Reform diS gp in E3
-reduction of FAD and then NAD+ |
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What does arsenite affect?
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-PDC and a-Ketogluterate-DH-complex
-Attacks lipoamide moiety of E2 and forms bidentate adduct which stops PDC and a-KDC |
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What is arsenate and what does it do?
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-Phosphate analog
-competes with phosphates in all rxn involving phosphate -Affects GAP-DH, forms another intermediate .: lose 1 ATP from glycolysis => not as bad as shutting down PDC tho (like arsenite does) |
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What are teh mechanistic advantages of multienzyme complexes?
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1) Rxn rate inc because distance btw active sites dec
2) Metabolic interm are channeled btw active sites -Reduces side rxns -protects labile intermediates 3) Coordinate control of enzyme activities: inhibit one enz, whole complex shuts down (easier to control) |
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How is pyruvate regulated?
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-PDC
-Lactate DH |
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What is the Warburg Effect?
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Cancer cells downregulate PDC and utilize Lactate DH.
Use only glycolysis instead of glycolysis + oxid P |
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What can Acetyl CoA be used for?
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Only CAC or FA synthesis (can't go back to glucose .: committed step)
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What are the 2 methods of regulatiokn of PDC?
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-Product inhibition: NADH inhibits rxn 5 and Acetyl-CoA inhibits rxn 3
-Covalent Modification: ->PDK: P E1 and inhibits the complex. PDK activated by NADH and Acetyl-CoA. PDK inhibited by: pyruvate, ADP, Ca2+ ->PDP: deP E1 so that it can be active. PDP activated by Ca2+ and Mg2+ |
