BIOCHEM Chp.10 TCA, ETC, & Oxidative Phosphorylation Flashcards
What are the steps of the TCA?
- Pyruvate → A-CoA via PDH
- A-coA → Citrate (OOA + A-CoA) via Citrate Synthase
- Citrate → Isocitrate via cis-Aconitate
- Isocitrate → alpha-Ketoglutarate via Isocitrate DH
- A-ketoglutarate → Succinyl-CoA via alpha-ketoglutarate DH
- Succinyl-CoA → Succinate via Succinyl-CoA Synthetase
- Succinate → Fumarate via Succinate DH
- Fumarate → Malate via Fumarase
- Malate → OOA via Malate DH
- OOA → A-CoA via Citrate Synthase
Where do the TCA, ETC, Glycolysis, and oxidative phosphorylation occur?
TCA/Kreb’s cycle - mitochondrial matrix
Oxidative phosphorylation - inner mitochondrial membrane
ETC - inner mitochondrial membrane
Glycolysis - cytosol
ATP Phosphorylation - cytosol and mitochondria
What are the main functions of TCA?
Oxidation of aCoA to CO2, water, GTP, NADH, FADH2
What are the 5 enzymes of the PDH?
- Pyruvate dehydrogenase
- Dihydrolipoyl transacetylase
- Dihydrolipoyl dehydrogenase
- Pyruvate dehydrogenase kinase
- Pyruvate dehydrogenase phosphatase
What inhibits the PDH?
accumulation of aCoA and NADPH
What is B-oxidation?
the use of FA to form aCoA.
What is the overall reaction of the PDH complex
pyruvate + CoA-SH + NAD+ –> a-CoA + CO2 + NADH + H+
What do dehydrogenases do?
transfer hydride ion (H-) to an electron acceptor, usually NAD+ or FAD
What is the diff b/w succinyl-CoA synthetase and citrate synthase?
citrate synthase doesn’t require energy input to form a solvent bond, but succinyl-CoA synthetase does
How much ATP is generated in glycolysis and TCA?
glycolysis: 7
TCA: 25
What activates and inhibits the PDH Complex?
PDH Kinase is activated by high ATP levels which has an inhibitory effect on the PDH Complex.
On the other hand, PDH Phosphatase is activated by high ADP levels and activates the PDH complex
What inhibits Citrate Synthase?
inhibited by ATP, NADH, S-Co-A, and citrate
What inhibits and activates Isocitrate DH?
ADP and NAD* are activators,
ATP and NADH are deactivators
What inhibits and activates a-KGDH?
ADP, NAD+, and Calcium are activators.
ATP, NADH, and S-Co-A are deactivators
What is the diff b/w aerobic and anaerobic respiration?
Aerobic respiration occurs in the mitochondria, while anaerobic respiration and fermentation occur in the cytosol
What is the purpose of the ETC?
The movement of protons from the mitochondrial matrix to the inner mitochondrial membrane space creates a greater concentration gradient of hydrogen ions that can be used to drive ATP Synthesis
What is the function of pyruvate dehydrogenase?
it oxidizes pyruvate, creating CO2; it requires thiamine pyrophosphate (vit B1/TPP) and Mg2+
What is the function of dihydrolipoyl transacetylase?
it oxidizes the remaining 2-carbon from TPP molecule using lipoic acid and transfers the resulting acetyl group to CoA forming aCoA
What is the function of Dihydrolipoyl dehydrogenase?
it used FAD to re-oxidize lipoic acid, forming FADH2. This FADH2 can later transfer electrons to NAD+ forming NADH that can feed into the ETC
What is the function of Pyruvate dehydrogenase kinase?
it phosphorylates PDH when ATP or aCoA levels are high, turning it off
What is the function of Pyruvate dehydrogenase phosphatase?
it dephosphorylates PDH when ADP levels are high, turning it on
What are the key enzymes in TCA?
- Citrate synthase
- Aconitase
- Isocitrate dehydrogenase
- a-ketoglutarate dehydrogenase complex
- Succinyl-CoA synthetase
- Succinate dehydrogenase
- Furmarase
- Malate Dehydrogenase
Describe B-oxidation
- FA couples w/CoA in the cytosol to form fatty aCoA, which moves into the intermembrane space
- the FA group is transferred to carnitine to form acyl-carnitine, which crosses the inner membrane
- the acyl group is transferred to a mitochondrial CoA to reform Fatty aCoA, which undergoes B-ox to form aCoA
What is the function of Citrate synthase?
couples a-CoA to OOA and then hydrolyzes the resulting product, forming citrate and CoA-SH.
What is the function of Aconitase?
isomerizes citrate to isocitrate
What is the function of Isocitrate dehydrogenase?
oxidizes and decarboxylates isocitrate to form a-ketoglutarate, generating the first CO2 and NADH of the TCA
What is the function of a-ketoglutarate dehydrogenase complex?
metabolizes a-ketoglutarate to succinyl-CoA, generating the second CO2 and NADH
What is the function of succinyl-CoA synthetase?
hydrolyzes the thioester bond in succinyl-CoA to form succinate and CoASH, generating the 1 GTP of the TCA
What is the function of Succinate dehydrogenase?
oxidized succinate to form fumarate, at the same FAD is reduced to form FADH2
What is the function of Fumarase?
hydrolyzes the alkene bond of fumarate, forming malate
What is the function of Malate Dehydrogenase?
oxidizes malt to oxaloacetate, generating the third and final NADH of the TCA cycle
How is Citrate synthase regulated?
ATP, NADH, citrate, and succinyl-CoA
What inhibits and activates Isocitrate dehydrogenase regulated?
ATP and NADH inhibit it, and ADP and NAD+ are activators
What inhibits and activates a-ketoglutarate dehydrogenase?
it inhibits ATP, NADH, and succinyl-CoA; it is activated by ADP and Ca2+
What are the steps of Complex I?
- NADH-CoQ oxidoreductase transfers electrons from NADH to FMN (the coenzyme of Flavoprotein).
- FMN is reduced to FMN2 via the iron-sulfur subunit and transfers the electrons
- Coenzyme-Q/Ubiquinone
Ubiquinone becomes ubiquinol/Coenzyme-QH2 - 4 protons are pumped across the intermembrane space
What are the steps of Complex II?
Succinate-CoQ oxidoreductase uses an iron-sulfur cluster to transfer electrons from succinate to FAD, and then CoQ, forming CoQH2. No protons are pumping occurs
What are the steps of Complex III?
CoQHS-cytochrome c oxidoreductase uses an iron-sulfur cluster to transfer electrons from CoQH2 to heme, forming cytochrome c as part of the Q cycle. Four protons are translocation to complex III
What are the steps of Complex IV?
cytochrome c oxidase uses cytochromes and Cu2+ to transfer electrons in the form of hydride ions (H-) from cytochrome c to oxygen, forming water. 2 protons pumped to complex IV
What is the function of the glycerol 3-phosphate shuttle?
electrons are transferred from NADH to dihydroxyacetone phosphate (DHAP), forming glycerol-3-phosphate, then moved to the mitochondrial FAD, forming FADH2
What is the function of the malate-aspartate shuttle?
electrons are transferred from NADH to oxaloacetate, forming malate. malate can then cross the inner mitochondrial membrane and transfer the electrons to NAD+, forming NADH
What is the final step of glucose breakdown under aerobic conditions??
oxygen is the final electron acceptor
Where is cytochrome C located?
the inner mitochondrial matrix
How many ATPs are produced from 1 FADH2 and NADH molecule?
FADH2= 1.5 ATP
NADH = 2.5 ATP
Why is it preferred to cleave thioester links than typical esther links in aerobic metabolism?
thioester hydrolysis has a higher energy yield
What is the function of nucleoside diphosphate kinase?
to convert GDP to GTP
Which complex does not contribute to the proton motive force?
complex II because no protons are pumped
Why does cytosolic NADH yield less ATP than mitochondrial NADH?
Electron transfer from the cytosol to the matrix can take more than one pathway
What is the purpose of the electrochemical gradient?
the proton motive force drives the phosphorylation of ATP by the F1 portion of ATP synthase
What is the purpose of the malate-aspartate and glycerol 3-phosphate shuttle?
NADH cannot enter the matrix, so these shuttles are its means to do so
What is the role of uncouplers?
they inhibit ATP synthesis without affecting the ETC
