Ch 10: Carbohydrate Metabolism 2 Flashcards
Acetyl-CoA
contains a high-energy thioester bond that can be used to drive other reactions when hydrolysis occurs
Pyruvate dehydrogenase complex
five enzyme complex in the mitochondrial matrix that forms acetyl-CoA from pyruvate but is also inhibited by acetyl-CoA and NADH
Pyruvate dehyrdrogenase (PDH)
oxidizes pyruvate, creating CO2; it requires thiamine pyrophosphate (vit B1, TTP) and Mg2+
Dihydropropyl transacetylase
oxidizes the remaining two-carbon molecule using lipoic acid, and transfers the resulting acetyl group to CoA, forming acetly-CoA
Dihydrolipoyl dehydrogenase
uses FAD to reoxidize lipoic acid, forming FADH2 which can later transfer electrons to NAD+, forming NADH that can feed into the electron transport chain
Pyruvate dehydrogenase kinase
phosphorylates PDH when ATP or acetyl-CoA levels are high, turning it off
Pyruvate dehydrogenase phosphatase
dephosphorylates PDH when ADP levels are high, turning it off
Acetyl-CoA can be formed from
- fatty acids, which enter the mitochondria using carriers
fatty acid couples with CoA in the cytosol to form fatty acyl-CoA, which moves to the intermembrane space
the acyl (fatty acid) group is then transferred to carnitine to form acyl-carnitine, which crosses the inner membrane.
the acyl group is then transferred to a mitochondrial CoA to re-form fatty acyl-CoA, which can undergo B-oxidation to form acetyl-Coa
- carbon skeletons of ketogenic amino acids, ketone bodies, and alcohol
Citric Acid Cycle takes place
in the mitochondrial matrix
Citric Acid Cycles main purpose is
to oxidize acetyl-CoA to CO2 and generate high-energy electron carriers (NADH and FADH2) and GTP
In CAC, Citrate synthase
couples acetyl-CoA to oxaloacetate and then hydrolyzes the resulting product, forming citrate and CoA-SH
regulated by negative feedback from ATP, NADH, succinyl-CoA, and citrate
In CAC, Aconitase
isomerizes citrate to isocitrate
In CAC, Isocitrate dehydrogenase
oxidizes and decarboxylates isocitrate to form alpha-ketoglutarate
generates the first CO2 and NADH of the cycle and is the
rate limiting step of the citric acid cycle so it is heavily regulated: ATP and NADH are inhibitors, ADP and NAD+ are activators
In CAC, alpha-ketoglutarate dehydrogenase complex
acts similarly to PDH complex, metabolizing alpha-ketoglutarate to form succinyl-CoA
generates second CO2 and NADH
inhibited by ATP, NADH, and succinyl-CoA
activated by ADP and Ca2+
In CAC, Succinyl-CoA synthetase
hydrolyses the thioester bond in succinyl-CoA to form succinate and CoA-SH. This enzyme generates the one GTP formed in CAC
In CAC, Succinate dehydrogenase
oxidizes succinate to form fumarate
flavoprotein (since covalently bonded to FAD) anchored to the inner mitochondrial membrane because it required FAD, which is reduced to FADH2, only one generated in cycle
In CAC, Fumarase
hydrolyzes alkene bond of fumarate, forming malate
In CAC, Malate dehydrogenase
oxidizes malate to oxaloacetate
enzyme generates the third and final NADH of the cycle
Electron Transport Chain
final common pathway that utilizes the harvested electrons from different fuels in the body; it is not the flow of electrons but the proton gradient that ultimately produces ATP
takes place on the matrix-facing surface of the inner mitochondrial membrane
NADH donates electrons to the ETC that are
passed from one complex to the next
as ETC progresses, reduction potentials increase until oxygen, which has the highest reduction potential, receives the electrons
Complex I (NADH-CoQ oxidoreductase)
uses an iron-sulfer cluster to transfer electrons from NADH to flavin mononucleotide (FMN) and then to coenzyme Q (CoQ) forming CoQH2. Four protons are translocated by complex I
Complex II (Succinate-CoQ oxidoreductase)
uses an iron-sulfer cluster to transfer electrons from succinate to FAD and then to CoQ forming CoQH2. No proton pumping occurs here
Complex III (CoQH2-cytochrome c oxidoreductase)
uses an iron-sulfer cluster to transfer electrons from CoQH2 to heme, forming cytochrome c as part of the Q cycle. Four protonns are translocated by Complex 3.
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. Two protons are translocated by Comple 4
NADH cannot cross the
inner mitochondrial membrane. This means shuttle mechanisms must be used to transfer electrons in the mitochondrial matrix
Glycerol 3-phosphate shuttle
electrons are transferred from NADH to dihyfroxyacetone phosphate (DHAP), forming glycerol 3-phosphate. these electrons are then transferred to mitochondrial FAD, forming FADH2
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 mitochondrial NAD+, forming NADH
What is the difference between Oxidative Phosphorylation and the ETC?
ETC is made up of the physical set of intermembrane proteins located on the inner mitochondrial matrix, and they undergo redox reactions as they transfer electrons to oxygen, the final electron acceptor. As electrons are transferred, a proton-motive force is generated in the intermembrane space. Oxidative phosphorylation is the process by which ATP is generated via harnessing the proton gradient, and it utilizes ATP synthase to do so
What links Oxidative Phosphorylation and the ETC?
By splitting up electron transfer into several complexes, enough energy is released to facilitate the creation of a proton gradient at many locations, rather than just one. Greater the proton gradient, the greater the ATP generation will be. Direct reduction of oxygen by NADH would release a significant amount of energy to the environment, resulting in inefficient electron transport
Proton-motive force
electrochemical gradient generated by the electron transport chain across the inner mitochondrial membrane. The intermembrane space has higher conc of protons than the matrix; this gradient stores energy which can be used to form ATP via chemiosmotic coupling
ATP synthase
enzyme responsible for generating ATP and ADP and an inorganic phosphate (Pi)
Under ATP synthase, the Fo portion is
an ion channel allowing protons to flow down the gradient from the intermembrane space to the matrix
Under ATP synthase, the F1 portion uses
the energy released by the gradient to phosphorylate ADP to ATP
Glycolysis generates
2 NADH and 2 ATP
Pyruvate dehyrogenase generates
1 NADH per molecule of pyruvate; since each glucose molecule forms two molecules of pyruvate, this complex produces a net of 2 NADH
Citric Acid Cycle generates
3 NADH, 1 FADH2, and 1 GTP (6 NADH, 2 FADH2, and 2 GTP per molecule of glucose)
Each NADH yields
2.5 ATP;
10 NADH forms 25 ATP
Each FADH2 yields
1.5 ATP;
2 FADH2 from 3 ATP
GTP are converted to
ATP
32 (30-32) ATP per molecule of glucose from
2 ATP from glycolysis
2 ATP (GTP) from citric acid cycle
25 ATP from NADH
3 ATP from FADH2
