Download BIOCHEMISTRY Electron Transport Chain

BIOCHEMISTRY
Electron Transport Chain/
Oxidative Phosphorylation
BIOB111
CHEMISTRY & BIOCHEMISTRY
Session 22
Session Plan
• Electron Transport Chain
• Oxidative
Phosphorylation
• Hormonal Control of
Carbohydrate
Metabolism
The Electron Transport Chain (ETC)
• Coenzymes NADH & FADH2 are oxidized in this process.
• Finally water is formed when e- & H interact with molecular O2.
O2 + 4e- + 4 H+
→
2H2O
ETC
• The enzymes & electron carriers of the ETC are located within
the inner mitochondrial membrane (IMM) as 4 distinct protein
complexes, tightly bound to the IMM.
• Complex I: NADH-Coenzyme Q Reductase
• Complex II: Succinate-Coenzyme Q Reductase
• Complex III: Coenzyme Q-Cytochrome c Reductase
• Complex IV: Cytochrome c Oxidase
• There are 2 mobile electron carriers – Coenzyme Q &
Cytochrome c – that shuttle electrons between the complexes &
are not tightly bound to the IMM.
The Electron Transport Chain (ETC)
• A series of biochemical reactions, in which e- & H+ from NADH &
FADH2 (produced in the CAC) are passed to intermediate
carriers & are finally accepted by molecular O2 to produce H2O.
• Transfer of e- – Redox reactions.
Stoker 2014, p871
Complex I
• NADH from CAC is the source of e- for this complex.
• It contains >40 subunits, including Flavin Mononucleotide
(FMN) & several Iron-Sulfur Proteins (FeSP).
• Facilitates transfer of e- from NADH to Coenzyme Q –
several steps & several intermediate carriers are involved.
Complex I
• The 1st step involves e- transfer from NADH to FMN.
• The NADH is oxidized to NAD+ (returns back to the CAC)
& passes 2H+ & 2e- to FMN, which is reduced to FMNH2.
Complex I
• NADH supplies both e- & one of the H+ ions (the other H+ comes
from the cellular solution)
• FMN accepts 2 H+ & 2 e-
Complex I
• The next steps involve transfer of electrons from reduced
FMNH2 through series of FeSPs.
• 2 molecules of FeSP are needed to accept the 2e- (1e- each).
• Fe3+ + e-  Fe2+
Complex I
• The final Complex I reaction involves conversion of
reduced 2Fe(II)SP to oxidized 2Fe(III)SP, as the 2 e- are
passed to the mobile CoQ which becomes reduced to
CoQH2.
Coenzyme Q
• A mobile e- carrier
• A Quinone derivative
Complex II
• Is much smaller than Complex I.
• Contains only 4 subunits,
including 2 FeSPs.
• Processes FADH2 from the CAC
• Succinate is converted to
Fumarate by this complex, while
reduced FADH2 is oxidized to
FAD (returns back to the CAC).
• CoQ is the final recipient of the efrom FADH2.
CoQH2 carries e- from both,
Complexes I & II to Complex III.
Stoker 2014,
Figure 23-15 p869
NADH is the substrate for Complex I &
FADH is the substrate for Complex II.
CoQH2 is the common product from both e- transfer processes.
Stoker 2014, Figure 23-13b p868
Complex III
• Contains 11 different subunits.
• The e- carriers in this complex include several FeSPs &
Cytochromes.
• Cytochromes
• Haeme-containing proteins, in which reversible oxidation &
reduction of an Fe atom occurs (similarly to FeSP).
• Various cytochromes – cyt a, cyt b, cyt c – differ by:
– Their protein constituents
– The manner in which the haeme is bonded to the protein
– Attachments to the haeme ring
Haeme
Stoker 2014, p869
Complex III
• The initial substrate for Complex III is CoQH2 carrying e- from
Complex I (from NADH) & Complex II (from FADH2).
• The electron transfer proceeds form CoQH2 → FeSP → cyt b →
another FeSP → cyt c1 → cyt c – another mobile carrier.
Stoker 2014, p870
Complex III
• The flow of e- through Complex III.
• The 2H+ from oxidation of CoQH2 go into cellular solution.
• All other redox reactions involve only electrons.
Stoker 2014, Figure 23-16 p870
Complex IV
• Contains 13 subunits, including 2 cytochromes – cyt a & cyt a3.
• The e- flow from cyt c to cyt a to cyt a3.
• In the final step of electron transfer, the e- from cyt a3 & H+ from
cellular solution combine with O2 to form H2O.
O2 + 4e- + 4 H+
→
2H2O
• It is estimated that 95 % of the O2 used by cells serves as the
final e- acceptor in the ETC.
Complex IV
• Each of the cyt a & cyt a3 also contain a Cu atom, in addition to
their Fe atoms.
Stoker 2014, Figure 23-17 p870
Summary of the Flow of Electrons Through
the 4 Complexes of the ETC
Stoker 2014, p871
Oxidative Phosphorylation (OP)
• The process by which ATP is synthesized from ADP & Pi, using
the energy released in the ETC.
• The central concept to OP involves coupled reactions.
• Coupled reactions – are pairs of concurrently occurring
biochemical reactions, in which energy released by one reaction
is used in another reaction.
• The OP & the oxidation reactions of ETC are coupled systems.
• The interdependence (coupling) of ATP synthesis & the ETC is
related to the movement of H+ across the IMM.
• Besides of e- transport, Complexes I, III & IV of the ETC have a
2nd function as “proton pumps” transferring H+ from the
mitochondrial matrix into the intermembrane space.
Complexes I,III & IV also function as “proton pumps”.
For every 2e- passed through the ETC, 10 H+ are
transferred from the matrix into intermembrane space.
Stoker 2014, Figure 23-18 p873
Oxidative Phosphorylation
• For every 2e- passed through the ETC, 4H+ cross the IMM
through Complex I, 4H+ through Complex III & 2H+ through
Complex IV – causes build-up of H+ in the intermembrane space.
• Increased [H+] in intermembrane space & decreased [H+] in the
matrix create a difference in [H+] forming a Electrochemical
(Proton) Gradient.
• Chemical gradient – difference in [H+]
• Electrical gradient – H+ has an electrical charge
Oxidative Phosphorylation
• H+ tend to flow from high [H+] to low [H+], however the IMM is
not permeable for H+.
• They pass through an enzyme complex – ATP-synthase within
the IMM & provide energy for ATP synthesis.
• The ATP-synthase complexes are the coupling factors that link
the ETC & OP.
• ATP-synthase has 2 subunits:
• F0 = channel for H+ flow
• F1 = ATP synthesis
Regulation of the ETC / OP
• The ETC is:
• Down-regulated by low levels of ADP, Pi, O2 & NADH.
• Up-regulated by high levels of ADP.
• Uncoupling agents
• Allows the ETC to take place but the energy that would usually
be used for ATP synthesis is released as heat.
• Thyroxine – thyroid hormone
• Thermogenin – a protein found in brown adipose tissue of
newborn mammals & hibernating mammals.
Stoker 2014, Figure 23-19 p874
ATP Production
• 1 mole of NADH form the CAC produces 2.5 ATP in the ETC/OP
• 1 mole of FADH2 from the CAC produces 1.5 ATP in the ETC/OP
• 1 mole of GTP is an equivalent to 1 mole of ATP
The total energy yield
in the CMP.
For every Acetyl CoA
entering the CMP
10 ATPs are produced.
Importance of ATP
• The constant conversion between ATP & ADP in metabolic
processes is the primary medium for energy exchange in
biochemical processes.
• Powers life processes – biosynthesis of essential compounds,
muscle contraction, nutrient transport, etc.
• Occurs in food catabolism & regenerates ATP.
The interconversion of ATP & ADP is the principal medium
for energy exchange in biochemical processes
Stoker 2013, Figure 23-19 p877
The relationships among
4 metabolic pathways that involve glucose
Stoker 2014,
Figure 24-16 p910
Glucose Metabolism
Stoker 2014, p912
Hormonal Control of Carbohydrate Metabolism
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INSULIN
Produced by β-cells of pancreas
51 amino acid polypeptide
Promotes utilization of glucose by cells
Its function is to lower blood glucose levels
Also involved in lipid metabolism
The release of insulin is triggered by high blood-glucose levels
The mechanism for insulin action involves insulin binding to protein
receptors on the outer surfaces of cells which facilitates the entry of
glucose into the cells
• Insulin also increases the rate of glycogenesis
Hormonal Control of Carbohydrate Metabolism
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GLUCAGON
29 amino acid peptide hormone
Produced by the α-cells of pancreas
Released when blood glucose levels are low
Principal function is to increase blood glucose
concentration by speeding up Glycogenolysis &
Gluconeogenesis in the liver
• Glucagon elicits the opposite effects of insulin
Hormonal Control of Carbohydrate Metabolism
• ADRENALIN
• Also called epinephrine (US)
• Released by the adrenal glands in response to anger, fear
or excitement
• Function is similar to glucagon – stimulates Glycogenolysis
• Primary target are muscle cells – promotes energy
generation for quick action
• It also functions in lipid metabolism
B vitamins & Carbohydrate Metabolism
• Many B vitamins function as coenzymes in
carbohydrate metabolism – without these the
body would be unable to utilize carbohydrates
as an energy source.
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6 B vitamins in carbohydrate metabolism:
Thiamin – as TPP
Riboflavin – as FAD, FADH2 & FMN
Niacin – as NAD+ & NADH
Pantothenic acid – as CoA
Pyridoxine – as PLP (pyridoxal 5-phosphate)
Biotin
Stoker 2014, Figure 24-19 p916
Readings & Resources
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Stoker, HS 2014, General, Organic and Biological Chemistry, 7th edn,
Brooks/Cole, Cengage Learning, Belmont, CA.
Stoker, HS 2004, General, Organic and Biological Chemistry, 3rd edn,
Houghton Mifflin, Boston, MA.
Timberlake, KC 2014, General, organic, and biological chemistry:
structures of life, 4th edn, Pearson, Boston, MA.
Alberts, B, Johnson, A, Lewis, J, Raff, M, Roberts, K & Walter P 2008,
Molecular biology of the cell, 5th edn, Garland Science, New York.
Berg, JM, Tymoczko, JL & Stryer, L 2012, Biochemistry, 7th edn, W.H.
Freeman, New York.
Dominiczak, MH 2007, Flesh and bones of metabolism, Elsevier Mosby,
Edinburgh.
Tortora, GJ & Derrickson, B 2014, Principles of Anatomy and Physiology,
14th edn, John Wiley & Sons, Hoboken, NJ.
Tortora, GJ & Grabowski, SR 2003, Principles of Anatomy and Physiology,
10th edn, John Wiley & Sons, New York, NY.