Module 09: Introduction to Metabolism (Part 02 - Stoker) Flashcards
Explain the overview of Catabolism.
(1) Bulk food is hydrolyzed in the stomach and small intestine to give small molecules
(2) Fatty Acids, monosaccharides, and amino acids are degraded in cells to yield acetyl CoA (Removal of amino group by transamination or oxidative deamination)
(3) Acetyl CoA is oxidized in the citric acid cycle to give CO2
(4) The energy is released in the citric acid cycle is used by the electron-transport chain to oxidatively phosphorylates ADP and produce ATP
This biochemical energy production takes place inside in the mitochondria (matrix) except reaction catalyzed by succinate DHG (part of inner mitochondrial membrane) which uses FAD
Citric Acid Cycle, CAC or Krebs cycle
What is the first intermediate of Citric Acid Cycle, CAC or Krebs cycle?
First intermediate of the cycle is citric acid, a tricarboxylic acid – therefore designated as Citric acid cycle or TCA
What happens in the Citric Acid Cycle, CAC or Krebs cycle?
In this stage acetyl group is oxidized to produce CO2 and reduced coenzymes NADH and FADH2
Most energy in the Citric Acid Cycle, CAC or Krebs Cycle is trapped where?
Most energy is trapped in reduced coenzymes NADH and FADH2
The energy produced from the Citric Acid Cycle (CAC) or Krebs Cycle?
Some energy produced in this stage is lost in the form of heat.
This is a series of biochemical reactions in which the acetyl portion of acetyl CoA is oxidized to carbon dioxide and the reduced coenzymes FADH2 and NADH are produced
Citric Acid Cycle
What is the other term of Citric Acid Cycle?
Also known as tricarboxylic acid cycle (TCA) or Krebs cycle
What are the two (2) important types of reactions?
(1) Reduction of NAD+ and FAD
(2) Decarboxylation
This reaction in the Citric Acid Cycle, CAC or Krebs cycle to produce NADH and FADH2.
Reduction of NAD+ and FAD
This reaction in the Citric Acid Cycle, CAC or Krebs cycle to produce carbon dioxide.
Decarboxylation
What does the Krebs Cycle or the Citric Acid Cycle produce.
The Krebs cycle also produces 2 ATP by substrate level phosphorylation, SLP from GTP per one glucose (Acetyl CoA + 3NAD+ + FAD + GDP + Pi + 2H2O —> 2CO2 + CoA-SH + 3NADH + 2H+ + FADH2 + GTP)
What are the eight (8) reactions of the Citric Acid Cycle?
Step 1: Formation of Citrate, C6
Step 2: Formation of Isocitrate, C6
Step 3: Oxidation of Isocitrate to a-ketoglutarate, C5 and formation of CO2: involves oxidation–reduction as well as decarboxylation
Step 4: Oxidation of Alpha-Ketoglutarate to succinyl CoA, C4 and Formation of CO2
Step 5: Thioester bond cleavage in Succinyl CoA and Phosphorylation of GDP
Step 6: Oxidation of Succinate, C4
Step 7: Hydration of Fumarate, C4
Step 8: Oxidation of L-Malate to regenerate Oxaloacetate, C4
The citric acid cycle is controlled by what?
The citric acid cycle is controlled by ATP and NADH
What happens when the ATP supply is high?
When ATP supply is high, ATP inhibits citrate synthase (Step 1 of Citric acid cycle)
What happens when the ATP supply is low?
When ATP levels are low, ADP is high, ADP activates citrate synthase ( ATP (-), ADP (+) citrate synthase)
What else does ADP and NADH control citric acid cycle (CAC) or the Krebs Cycle?
Similarly ADP and NADH control isocitrate dehydrogenase: NADH (-), ADP (+) isocitrate DHG
(1) NADH acts as an inhibitor
(2) ADP as an activator.
This is used to regenerate NAD+ and FAD. This facilitates the passage of electrons trapped in FADH2 and NADH generated by citric cycle
Electron Transport Chain (ETC)
Explain the nature of Electron Transport Chain (ETC)?
intermediate carriers (protein and non-protein) aid the transfer of electrons and hydrogen ions from NADH and FADH2
The ultimately receiver of electrons is __________.
Molecular Oxygen
Where did the Electron Transport Chain (ETC) get its name?
The ETC (respiratory chain) gets its name from the fact electrons are transported to oxygen absorbed via respiration
What is the overall ETC reaction?
2H+ + 2e- + ½ O2 –> H2O + energy
Energy is used to synthesize ATP in ___________________.
oxidative phosphorylation, OP, where 2 hydrogen ions, 2 electrons, and one half-oxygen molecule react to form the product water
The energy released is coupled with what?
the formation of 2.5 ATP molecules per every molecule of NADH processed through ETC
The enzymes and electron carriers for ETC are located along what?
inner mitochondrial membrane
The Electron Transport Chain (ETC) is organized into what?
four distinct protein complexes and two mobile carriers, where the four protein complexes tightly bound to membrane
What are the four (4) distinct protein complexes?
(1) Complex 1: NADH - Co Q reductase
(2) Complex II: Succinate - Co Q reductase
(3) Complex III: Co Q - cytochrome b c1 reductase
(4) Complex IV: Cytochrome a a3 oxidase
(5) Two mobile electron carriers
What are the two (2) mobile electron carriers?
Coenzyme Q and cytochrome c
What is complex 01?
NADH - Co Q reductase
This is the source of electrons for this complex.
NADH + H+ from citric acid cycle
What does the Complex 1: NADH-Coenzyme Q Reductase?
It contains flavin mononucleotide (FMN) and several iron-sulfur protein clusters (FeSP)
What does the FeSP contain in Complex 1: NADH-Coenzyme Q Reductase?
Fe not in heme but attached to S of cysteine in the protein
What is the net result from Complex 1: NADH-Coenzyme Q Reductase?
Net result: Facilitates transfer of e- from
(1) NADH to coenzyme Q reducing it to QH2
NADH + H+ + Q —> NAD + + QH2
What is complex 2?
Complex II: Succinate-coenzyme Q Reductase
This is smaller than complex 1 and it contains only four subunits including two iron-sulfur protein clusters (FeSP)
Complex II: Succinate-coenzyme Q Reductase
What does Complex II: Succinate-coenzyme Q Reductase contain?
Contains only four subunits including two iron-sulfur protein clusters (FeSP)
What happens to succinate in Complex II: Succinate-coenzyme Q Reductase?
Succinate is converted to fumarate (Krebs) by this complex.
What is generated from Complex II: Succinate-coenzyme Q Reductase?
FAD
In Complex II: Succinate-coenzyme Q Reductase, this is the final recipient of the electrons from FADH2?
CoQ
What is the chemical formula for Complex II: Succinate-coenzyme Q Reductase?
FADH2 + Q —–> FAD + QH2
Explain the process of Complex II: Succinate-coenzyme Q Reductase
(1) CoQH2 carries electrons from both complexes 1 and 2 to complex 3
(2) NADH is the substrate for Complex 1 and FADH2 is the substrate for complex 2. CoQH2 is the common product from both the electron transfer processes.
What is complex 3?
Complex III: Coenzyme Q – Cytochrome c Reductase
How many different subunits does Complex III: Coenzyme Q – Cytochrome c Reductase contain?
Complex III contains 11 different subunits
What are the electron carriers in Complex III: Coenzyme Q – Cytochrome c Reductase?
Several iron-sulfur proteins and cytochromes
In Complex III: Coenzyme Q - Cytochrome c Reductase, this is a heme iron protein in which reversible oxidation of an iron atom occurs?
Cytochrome
Explain the chemical formula for Complex III: Coenzyme Q – Cytochrome c Reductase?
Fe+3 <—> Fe+2
(Various cytochromes, e.g., cyt a, cyt b, cyt c, differ from each other)
Explain the role of CoQH2 in Complex III: Coenzyme Q – Cytochrome c Reductase
Electron Movement through the complex 3 is initiated by the electron carrier CoQH2, where electrons are passed down to cyt C.
What is complex 4?
Complex IV: Cytochrome c Oxidase
How many subunits does Complex IV: Cytochrome c Oxidase contain?
Contains 13 subunits including two cytochromes
Explain the process in Complex IV: Cytochrome c Oxidase?
(1) The electrons flow from cyt c to cyt a to cyt a3
(2) In the final stage of electron transfer, the electrons from cyt a3, and hydrogen ion (H+) combine with oxygen (O2) to form water
What is the chemical formula for Complex IV: Cytochrome c Oxidase?
½O2 + 2H+ + 2e- –> 1 H2O
O2 + 4H+ + 4e- –> 2 H2O
How many percentage of O2 is used by cells that serves as the final e- acceptor for the ETC?
95%
How do electrons pass in Complex IV: Cytochrome c Oxidase?
The electron transfer pathway through complex 4. Electrons pass through both copper and iron centers and in the last step interact with molecular O2. Reduction of an O2 molecule requires the passage of four electrons through complex 4 one at a time.
Explain the summary of the flow of electrons through four complexes in the electron transport chain.
(1) Both hydrogen and electrons from NADH and FADH participate in the reactions involving enzyme complexes 1 and 2.
(2) Following the formation of CoQH2 hydrogen ions no longer directly participate in enzyme complex reactions; that is they are not passed further down to the enzyme complex chain
(3) Instead, they become part of the cellular solution, where they participate in several reactions including the process by which ATP is synthesized
This is the process by which ATP is synthesized from ADP and Pi using the energy released in the ETC - coupled reactions
Oxidative phosphorylation
These are pairs of biochemical reactions that occur concurrently in which energy released by one reaction is used in the other reaction.
Coupled Reactions
What are examples of coupled reactions or systems?
oxidative phosphorylation and the oxidation reactions of the electron transport chain are coupled systems
This is related to the movement of protons (H+ ions) across the inner mitochondrial membrane
coupling of ATP synthesis
What is the second function of complexes 1, 3 and 4 in oxidative phosphorylation?
“proton pumps” transferring protons from the matrix to the intermembrane space (IMS)
What is the chemical formula for COMPLEX 1 in Oxidative phosphorylation?
(NADH + H+) + CoQ + 4 H+(matrix) —> NAD+ + CoQH2 + 4 H+(intermembrane)
What is the chemical formula for COMPLEX 2 in Oxidative phosphorylation?
2 CoQH2(site 1) + CoQ(site 2) + 2 Cyt c(ox) + 2 H+(matrix) -> 2 CoQ(site 1) + CoQH2(site 2) + 2Cyt c(red) + 4H+(intermembrane)
What is the chemical formula for COMPLEX 3 in Oxidative phosphorylation?
2 cytochrome c(red) + ½O2 + 4 H+(matrix) -> 2 cytochrome c(ox) + 1H2O + 2 H+(intermembrane
What happens for every two electrons that pass through the ETC?
For every two electrons passed through ETC, four protons cross the inner mitochondrial membrane through complex I, four through complex III and two more though complex IV
What would happen when there is a proton flow in the ETC?
This proton flow causes a buildup of H+ in the intermembrane space (IMS), creating a H+ gradient
What would happen when there is a gradient buildup in the ETC?
The gradient build-up would push the H+ ions back through inner membrane-bound ATP synthase: This high concentration of protons passing through ATP synthase provides the energy for ATP synthesis
What happens in the mitochondrial matrix?
Inside the mitochondrial matrix, the electron transport chain and the ATP synthase nanomachine are tightly couple systems to provide energy for metabolism
This forms the channel through which protons would flow from the IMS back to the matrix. It spans the inner mitochondrial membrane.
Fo
This is the subunit with catalytic activity. It catalyzes the phosphorylation of ADP to form ATP.
It looks like a door knob.
F1
What does the formation of ATP do the flow of protons?
Formation of ATP accompanies the flow of protons from the intermembrane space, IMS back into the mitochondrial matrix
What happens in the inner mitochondrial space when there is a proton flow?
The proton flow results from an electrochemical (proton) gradient across the inner mitochondrial membrane
For each mole of NADH oxidized in the ETC, how many moles of ATP is formed?
2.5 moles of ATP* are formed.
For each mole of FADH2 oxidized in the ETC, how many moles of ATP is formed?
only 1.5 moles of ATP* are formed.
each mole of GTP formed in Krebs is equivalent to ______ mole of ATP.
one mole of ATP
How many molecules of ATP are produced for each acetyl CoA catabolized (1 NADH -> 2.5, 1 FADH2 -> 1.5 ATP?
10 moles of ATP
These are the principal medium for energy exchange in biochemical processes (ATP cycle) in metabolic processes?
cycling of ATP and ADP
In this, ATP synthesis is coupled to the hydrolysis of a high energy compound.
Substrate level phosphorylation
This is the synthesis of ATP when coupled with the electron transport chain/ETC
Oxidative phosphorylation
> 90% of inhaled oxygen via respiration is consumed during _______________________.
oxidative phosphorylation
Remaining O2 are converted to several _____________________with in the body.
highly reactive oxygen species (ROS)
Give examples of highly reactive oxygen species (ROS)
(1) Hydrogen peroxide (H2O2)
(2) Superoxide ion (O2-) and
(3) Hydroxyl radical (.OH)
(4) Superoxide ion and hydroxyl radicals have unpaired electron and are extremely reactive
What is the benefit highly reactive oxygen species (ROS)
White blood cells produce a significant amount of superoxide free radicals via the following reaction to destroy the invading bacteria and viruses.
2O2 + NADPH –> 2O2- + NADP+ + H+
About 5% of ROS escape destruction by ___________________ and __________________.
superoxide dismutase and catalase enzymes
What are the anti oxidants?
(1) Vitamin K
(2) Vitamin C
(3) Glutathione (GSH)
(4) Beta-carotene
