part 7 lecture mitochondria

8/7/2019 Part 7 Lecture Mitochondria

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MITOCHONDRIA:STRUCTURE AND FUNCTION

MitochondriaIndividual, bean-shaped organelles ranging from 1-4 µm in lengthMay also appear as highly branched,interconnected tubular networkHave the ability to fuse with one another (fusion),or split in 2 (fission)Functions:

1.Generates ATP2.Synthesis of Heme groups and certain amino acid3. Plays a vital role in the uptake and release of Ca ++

4.Regulates apoptosis



Mitochondrial membranes1.Outer mitochondrial membrane

Encloses the mitochondrion, serving its outer

boundaryComposed of approximately 50% lipid by weightContains a mixture of enzymes involved in diverseactivities like oxidation of epinephrine,degradation of tryptophan, and elongation of fattyacidsContains “porins”

2. Inner mitochondrial membraneHas very high protein/ lipid ratio (>3 : 1)Devoid of cholesterolRich in cardiolipin which facilitates the activity of the proteins involved in ATP synthesis

Highly impermeableSubdivided into 2 interconnected domains:a. Inner boundary membrane

>lies just inside the outer membrane, forming adouble membrane outer envelope>rich in CHONs responsible for import of mitochondrial CHONs

b. Internal cristal membrane

CristaeA series of invaginated sheets of deep foldspresent within the inner mitochondrial membrane

Responsible for the role of mitochondria as energytransducers (ATP synthase)



Cristae junctionsA narrow junctions which joins the 2interconnected domains of the inner mitochondrial membrane

Mitochondrial compartments:1. Intermembrane space

Region between the outer and inner membraneContains CHONs which initiates apoptosis

2.MatrixRegion inside the inner membraneHas a gel like consistency owing to the presenceof high concentration of H 2 O soluble CHONsContains ribosomes and DNA

Energy Transducing Mechanism

I. GlycolysisOccurs in the cytosol



Net Reaction:Glucose + 2NAD + + 2ADP + 2 Pi

→ 2 Pyruvate + 2 ATP + 2 NADH + 2H + + 2H 2 O

Fates of Pyruvate:

Fates of NADH:The electrons of NADH are used to reduce a low-molecular-weight metabolite that can either:

1. Enter the mitochondrion by a pathway calledmalate-aspartate shuttle) and reduce NAD + toNADH

2. Transfer its electron to FAD to FADH 2 by a

pathway called the glycerol phosphate shuttle



II. Kreb’s cycle/ Tricarboxylic acid cycle/ Citirc Acidcycle

> occurs in the mitochondrial matrix



Net Equation:2 Acetyl CoA + 4H2O + 2FAD + 6 NAD + + 2GDP + 2Pi

→ 4CO2 + 2FADH 2 + 6NADH + 6H + + 2GTP + 2 HS-CoA

III. Electron Trasport Chain (Respiratory Chain)Location: inner mitochondrial membraneCoupled with proton translocation from the matrixto the intermembrane space

Electron carriers: With the exception of ubiquinone, all areprosthetic groups (non-amino acid components

that are tightly associated)Types:



1.Flavoproteins With attached FAD (flavin adenine dinucleotide) or FMN (flavin mononucleotide)Capable of accepting and donating two protons

and 2 electrons

2.CytochromesContain heme prosthetic groups3 distinct types : a, b & cAble to accept and donate 1 electron

3. 3 copper atomsAccept and donate a single electron as theyalternate between the Cu ++ and Cu + states

4.Ubiquinone (UQ or coenzyme Q)Lipid-soluble molecule containing isoprenoid units

Able to accept and donate 2 electrons and 2protons

5. Iron-sulfur proteinsIron are linked to inorganic sulfide ions as part of iron-sulfur center Able to accept and donate only a single electron

Electron Transport Complexes:1.Complex I (NADH dehydrogenase)

Transfer electrons from NADH to FMN to Fe-S andfinally to ubiquinone embedded in the lipid bilayer

2. Complex III (cytochrome bc 1 )Transfer electrons from:



a. UQ to Fe-S to cyt c 1

b.UQ to cyt b

3.Complex II (succinate dehydrogenase)

Feeds lower-energy electrons from succinate toFAS and then to UQNot accompanied by proton translocation

4.Complex IV (cytochrome c oxidase)Transfer electrons from reduced cytochrome tooxygen forming H

2O

To reduce a whole molecule of O2:4 cyt c 2+ + 4 H+ + O 2 → 4 cyt c + 2 H 2 O

For every molecule of O 2 reduced to 2 H 2 O bycytochrome oxidase, 4 H + are being translocated.



IV. Translocation of Protons and establishment of aProton Motive Force

Proton motive force

Has 2 components: 1. Voltage (80%)2. pH gradient (20%)

Maintenance requires that the inner mitochondrialmembrane remains impermeableUsed to drive ATP synthesisOther functions:1. Uptake of ADP into the mitochondtion in

exchange for the release of ATP to the cytosol2. Uptake of phosphate and Calcium ions3. Import of mitochondrial proteins

2,4 dinitrophenol (DNP)A certain lipid-soluble agents that enables

continuation of oxidation of substrates withoutbeing able to generate ATPUncouples glucose oxidation and ADPphosphorylation by combining with protons andcarrying them across the inner mitochondrialmembrane down their electrochemical gradient

Uncoupling proteins (UCPs)Acts as natural/endogenous uncouplersAbundant in brown adipose tissue of mammals,which functions as a source of heat productionduring exposure to cold temperatures



V. Oxidative phosphorylationSteps:

1. Substrates are oxidized and the electrons aretransferred to coenzymes forming NADH or FADH 2 .

These high energy electrons are then transferredthrough a series of electron carrieirs of the ETS.The energy released is used to traslocate protonsfrom the matrix to the intermembrane space,establishing a proton electrochemical gradientacross the inner mitochondrial membrane.

2. The protons move down the electrochemicalgradient, through an ATP-synthesizing complex.The energy stored in the gradient is used tosynthesize ATP



ATP synthaseThe ATP synthesizing enzymeContains 2 distinct parts:1. F 1 head

> projects into the matrix> contains the catalytic site> consist of 5 different polypeptides (α 3 β 3 δγε)

2. F 0 base> Embedded in the lipid bilayer and forms achannel through which protons are conductedfrom the intermembrane space into the matrix> Consist of 3 different polypeptides

Binding Change Mehanism:1. Movement of protons induces rotation of the γ

subunit, which will change the conformation of F 1

catalytic sites2. The energy released by the movement of protons

is not used to drive ADP phosphorylation directlybut principally to change the binding affinity of theactive site for the ATP product

3.Each active site progresse successively through 3distinct conformation that have different affinitiesfor substrates and producta.“L” or “loose” conformation (ADP and Pi are

loosely bound)b. “T” or “tight” conformation (ADP and Pi or ATP

are tightly boundc. “O” or open conformation (has very low affinity

for nucleotides, allowing release of ATP)



Mitochondrial mutationsLikely to accumulate in cells that remain in thebody for long periods of time (e.g., nerve andmuscle tissues)Has been implicated in premature aging

Parkinson’s DiseaseNeurodegenerative disease associated with

mitochondrial mutation leading to decrease inComplex I activity

Aerobic vs. anaerobic exerciseAnaerobic Aerobic

1. Example Lifting weights, sprints Bicycling, fast walking2. Types of musclefiber

Fast twitch fibers Slow twitch fibers

3. Generation of ATP Glycolysis Aerobic respiration4. Substrate utilized Glycogen stores Initially glycogen but

eventually fatty acidfrom adipose tissues

5. Lactic acidaccumulation

Yes No

6. Sustainability Short Longer

part 7 lecture mitochondria

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