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 Sheet 4, Dr.Nafeth, by Zain Al-Thaher 12\2\2012

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Majed Sharayha

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PostSubject: Sheet 4, Dr.Nafeth, by Zain Al-Thaher 1222012   Tue Feb 14, 2012 5:29 am

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Oxidative Phosphorylation
We said before that the Electron Transport Chain is a sequential process, if we disrupt a complex disruption to the e` transport as a consequence proton disruption.
We could make a partial or complete inhibition ;
No NADH dehydrogenase; partial inhibition.
To know whether it’s a complete or partial inhibition we should see how does it affect e` transport, H+ transport ….
Cyanide (binds Iron in Heme in cytochrome C and prevents O2 from binding with it, which is the terminal e` acceptor)
Cyanoglycosides; sugars attached to Cyanide(mentioned in the slides) such as Amygdalin that is found in Almonds, Seeds of the fruit (peaches, apricot) cherries, soy beans … (also in the slides).
We have to know that the patient with Cyanide poisoning has a Bitter Almond smell.
Cyanide poisoning happens after exceeding a certain limit.

OXPHOS. Diseases:
Genetic (DNA) : the mitochondrial DNA is small, circular, double stranded, encodes 13 subunits ( 7 in complex 1 , 1 in complex 3 , 3 in complex 4 , 2 in ATP-Synthase ) mRNAs of the mitochondrial DNA.
Disease inherited is Maternal.
Cells divide mitochondria divides affects the mutation Replication division but not all the genetic material.
Heteroplasmy: not all the tissues of the body have the same problem (variation of the expression).
Disease Pathology and Age:
If the patient has a genetic disorder in the mitochondria with age, Autosomal somatic mutation in the DNA of the nucleus (accumulation of more problems) and the patient starts to feel that his disease is in progression.
Threshold expression; when a tissue reaches a point where it can’t give ATP as required Failure of the tissue, such as the CNS and all the tissues that use ATP in high amounts.

2. Genetic mutations in the nucleus:
Usually autosomal recessive.
The expression of the mutation is high in the high ATP demanding organs.
The Dr. showed us a table that contains diseases and he literally said “ma behemni t3rafo kter 7aki bs b shakel 3am, there are genetic mutations in the mitochondria that affect the subunits and proteins in the oxidative phoshpo. And what are the results , had illi beddi t3rafo bdoon tafaseel “.

Coupling of the ET and ATP synthesis:
E` transport is coupled with proton transport.
When the levels of NADP increases H+ influx at the ATP-Synthase level to make ATP.
When the protons go inside through the membrane ATP is synthesized, the electrochemical gradient increases across the membrane no more generation to the ATP , so we have to keep it to a certain level by increasing the process of Oxid. Phospho. To increase the pumping of the protons.
e` transport increases O2 consumption increases to take more e`s substrates of the rxn increase (NADPH + ADP) generation of ATP burn more fuel more NADH.
ATP is present in cells in certain limits but in high amounts in the skeletal muscles because the amount of ATP could decrease at any time because their movement is sudden from rest, though the drop is no more than 20% till the cells catch up and regenerate ATP. At the heart for an example the ATP levels are always the same regardless of what happens because high introduction of Ca+2 more heart beats stimulates the enzymes of the Krebs cycle generates NADH ATP.

Uncoupling of ET :
Physiological; proton leak across the membrane heat generation.
The uncoupling decreases the ATP more O2 consumption to generate ATP.
Chemical; Ionophores : Lipid soluble compounds that can transport in the membrane and take ions with it from outside to inside the matrix.
-More generation to the Heat and less ATP.
-An example of the Ionophores; Dinitrophenol(people on a diet used to take it)(the dr. pointed at its structure)
-it can travel through the membrane takes protons with it generate more heat burning of the fuels in the body.
-People stopped using it because of the Hyperthermia(it is unexpectable in the body and differs from one person to another and with age also it can shut down organs).
-Another example is Oligomycin, it is an antibiotic, binds the C subunit and blocks the proton transport from intermembranous space to the matrix. The ATP synthase doesn’t work no ATP.

Uncoupling Proteins (UCPs) :
-they are 5 types, each for a specific tissue.
-type I in Brown Adipose tissue (mainly in infants).
-type II in most cells.
-type III in Skeletal muscles.
-types IV and V in the Brain.
-when we are feeling cold hypothalamus sends a message to the ANS sympathetic nerves release nor epinephrine to cells release triglycerides release F.A.s (enhance thermogenin which is an UCP found in brown tissue) takes H+ to the Matrix generation of heat.
-UCPs decrease e` transfer decrease coenzyme Q + Ubiquinone which accepts 1 or 2 e`s free radical and affects the health of the cell.
-proton leak back through the membrane heat electrochemical gradient decreases but we have to keep it to a certain level by using 20% of the BMR.

Transportation of the molecules and compounds :
“ The Dr. read the slide”
-most of the transport is Isotransport.
-Ca+2 needs ATP to transfer it outside (usually).
-the inner mitochondrial membrane is tight so we need specific transporters for the electrolytes unlike the outer mitochondrial membrane that is leakier.
-any compound that it less than or equal to 6000 Daltons can pass through VDAC (Voltage Dependent Anion Channels) on the outer membrane.
-mitochondrial permeability of the transitional pores, they function when the cell dies.
-matrix Ca+2 increases or low O2 activates their openings by ATP translocases attached to VDAC one on the outer membrane and one on the inner membrane so a connection between outer and inner membranes i.e. cytosol to matrix.
When the cell wants to die by Apoptosis or Necrosis the pore opens the influx of cations and anions increases to the matrix the electrochemical gradient increases shutting down of the oxid. Phospo. Cell death.

Answers : 1.D 2.B 3.B 4. ?? 5.C 6.C 7.B

DONE BY: Zain AL-Thaher.

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