etc part ii & lip met

ETC part II & Lip Met الفريق الطبي الأكاديمي

كلــية الطب البشري

البلقاء التطبيقية / المركز

6102/6166أ حياها و من

Done & Corrected By :-

Obadah Abubaker & Rasha Rakan

Metabolic energy و من أحياها

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تحته خطينكلام السلايدات الاحمر ، (Nabeelكلام الدكتور )، (slideكلام السلايدات )

الصور يوجد تحتها شرح مفصل

From the last lecture

Iron sulfur clusters present in complex 1,2,3*

complex 4 (cytochrome oxidase) They are not present in

instead there’s Copper (Cu)

Heme group in cytchrom C and succinate has no oxygen

that is difference between it and the heme group in

hemoglobin and myoglobin

and ulfur containing amino acids are cysteineS

methionine

Before the discovery of Chemiosmotic theory ATP was *

thought to be synthesized by substrate level

phosphorylation.

The rate of oxidative phosphorylation (the formation of

ATP) depends on the concentration of ADP


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هناك وهو ما اله لزوم mitochondrial matrixيتكون في ال ATPال

بحدث glycolosis)مثال: ال cytosolلانه العمليات رح تصير في ال

ADP -ATP( فاحنا بدنا اياه يطلع برى فبيطلع عن طريق cytosolفي ال

Translocase كما شرح في المحاضرة الماضية

ndrial mitochoتشير إلى ال mوال Cytosolتشير الى cال

matrix.

* Rotenone and Amytal inhibits complex I (FMN) it

doesn’t inhibit ETC completely because electrons are still

coming from complex II

Myxothiazol and Antimycin A inhibit the first carrier

(CoQ) complete inhibition

Carbon monoxide (CO), Azide (N3-), Cyanide (CN-)

inhibits complex IV ( cytochrome oxidase, Cyt aa3)

The last electron acceptor is O2.

The ultimate aim of metabolism is to produce energy

and water .


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1-Brown adipose tissue , thermogenin ,UCP*

:hysiological uncouplersare p

and thus the proton gradientThey prevent

pumping the concentration of protons remains low by

present in infants and and are matrixproton into the

Hibernated animals

chemical uncoupler*

وبشتغل عنفس المبدأ )Dinitrophenol -2,4(ومثال عليه

eightrapid loss of w

ملاحظة : كل ما سبق هو مجرد إضاءات لأمور شرحت بالتفصيل في

المحاضرة السابقة لكن الدكتور عاد وشرحهم سريعا الرجاء الاعتماد

بشكل أساسي على ما ورد في المحاضرة السابقة لما فيه من تفصيل.


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Shuttle Mechanisms

Shuttle mechanisms: transport metabolites between

mitochondria and cytosol

عشان mitochondriaكان بدو يدخل ال pyruvate,ال gluconeogenesisمثل ال

وبعدها يرجع مرة malateيتحول ل oxaloacetateوال oxaloacetateيتحول ل

ما بقدر يرجع مرة ثانية لإنه pyruvateلأنه ال glucoseثانية يطلع لبرى عشان يعطينا

فبالتالي بيدخل لل ,irreversible reactionهو pyruvate kinaseال

mitochondria وبيرجع مرة ثانية

o mechanisms :wWe have t

1.Glycerol phosphate shuttle

• glycolysis in the cytosol produces NADH should enter the mitochondria to reach ETC because it won’t produce ATP in the cytosol.

• NADH does not cross the mitochondrial membrane, but glycerol phosphate and dihydroxyacetone phosphate do so it needs a carrier

• by means of the glycerol phosphate shuttle, 2 ATP are produced in the mitochondria for each cystolic NADH


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is aldose, the body handles aldehyde GPis ketose and DHAP

better than ketone that can be turned into acids, that’s why we

Cytosolic glycerol by the enzyme “ GPto DHAPtransform

”phosphate dehydrogenase

, then enters the NADHnow carries the electron of GP

l matrix mitochondria

is then transformed into DHAP by the enzyme GP

and thus ” mitochondrial glycerol phosphate dehydrogenase“

2FADH othat turns int FADgiving the electron to the carrier

will give us 2 ATP (not 1.5 ATP) through ETC 2FADH

here gives us 2 ATP instead of 3, because it NADHThat’s why

then GPdoesn’t give the electron directly to ETC, but through

2FADH

2ATP) There lose in ATP (NADH


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2.Malate-aspartate shuttle • found in mammalian kidney, liver, and

heart • Involved in transamination reactions • malate crosses the mitochondrial

membrane, while oxaloacetate cannot • the transfer of electrons from NADH in

the cytosol produces NADH in the mitochondria

• with the malate-aspartate shuttle, 3 mitochondrial ATP are produced for each cytosolic NADH


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, by the enzyme malate-Le is transformed into Oxaloacetat

carries the malate ” and thus cytosolic malate dehydrogenase“

.NADHelectron of

crosses the mitochondrial membrane, and transformed Malate

mitochondrial malate by the enzyme “oxaloacetate to

and sthe electron +NAD”, thus giving the dehydrogenase (CAC)

that gives 3 ATP (not 2.5) NADHbecomes

and Aspartate-Ltransform to Glutamate -Land Oxaloacetate

mitochondrial aspartate by the enzyme “ ketoglutarate-α

” aminotransferase

moves to the cytosol and ketoglutarate -αand Aspartate -L

Glutamate -Land Oxaloacetatereact with each other and give

”tosolic aspartate aminotransferasecyby the enzyme “

3ATP) there is no loss of ATP (NADH

Summary

• Shuttle mechanisms transfer electrons, but not NADH, from the cytosol across the mitochondrial membrane

• In the malate-aspartate shuttle, 3 molecules of ATP are produced for each molecule of cytosolic NADH, rather than 2 ATP in the glycerol-phosphate shuttle, a point that affects the overall yield of ATP in these tissues.


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New Chapter:~ Lipid metabolism:

Lipids vs. Carbohydrates A gram of nearly anhydrous fat stores more than six

times as much energy as a gram of hydrated glycogen,

which is likely the reason that triacylglycerols rather

than glycogen were selected in evolution as the major

energy reservoir.

The glycogen and glucose stores provide enough energy

to sustain biological function for about 24 hours,

whereas the triacylglycerol stores allow survival for

several weeks.

Lipids give us high energy, and lipocytes (fat cells) volume can

expand up to 6 folds but their amount is fixed by the age of 20-

21.

lipids are stored reduced (when we oxidize lipids they will give

us high energy) and anhydrous (without water)

carbohydrates needed water to be stored as glycogen, each

gram of glycogen needs 1-1.5 gram of water. (muscles & liver)

lipid tissue is around the organs and under the skin (superficial).

Fasting and starvation for long periods of time we depend on

lipids, lipids then will then transform into ketone bodies that

will turn into acids that will create problems for the brain as we

will study later.


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Fatty Acids and Energy

Fatty acids in triacylglycerols are the principal storage

form of energy for most organisms

– their carbon chains are in a highly reduced form

– the energy yield per gram of fatty acid oxidized is greater than that per gram of carbohydrate oxidized

Lipids have high energy because it is reduced and anhydrous.

Lipids are stored as triglycerides, when we degrade triglycerides

(bound on the we get glycerol (the backbone) and fatty acids

glycerol).

fatty acids are the same type Simple triglyceride

fatty acids are different types (more Mixed triglycerides

common)

4kcal/g Alcohol 9 kcal/g Carbohydrates & proteins Lipids

7 kcal/g

C6 H1 2 O6 + 6 O2

CH3 ( CH2 ) 14 COOH + 2 3 O2

6 CO2 + 6 H2 O

1 6 CO2 + 1 6 H2 O

-15.9

-38.9

Palmitic acid

Glucose

Energy(kJ•mol -1)

16

carbon

atoms


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Chylomicron Formation

Free fatty acids and monoacylglycerols are absorbed by intestinal epithelial cells. Triacylglycerols are resynthesized and packaged with other lipids and apoprotein B-48 to form chylomicrons, which are then released into the lymph system. Absorption of lipids is done by Chylomicron Formation. Lipids are in the form of micelles inside of the intestine. Lipase degrades triglycerides into fatty acids and monoacylglycerols, who then are absorbed by mucosal cells. They synthesize triglycerides again and then proteins are added to them so they form Chylomicrons (to the lymphatic system).

mucosalلل بدخل ينبعد micellesعلى شكل وابكون ntestineiداخل ال يعني cells وبعدها بينضفلهم بروتينات وبتحولوا لChylomicron وبعدها بتروح ال

sonChylomicr للlymphatic system بالتحديد للlacteals فبتروح للliver ورح ييطلع منها الfatty acids وتتوزع وسيتم التفصيل بحيثيات

الموضوع لاحقا ان شاء الله 83عودة للمعلومات من الريكورد يجدها في الدقيقة أراد اللمن :ملاحظة


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Degradation of lipids is a result of catabolic hormones

(epinephrine) or exercise (need of energy)

reaction:It’s a cascade

receptor complex activates Adenylyl cyclase that -Hormone

(2nd messenger). transforms ATP to cAMP

cAMP activates Protein kinase that phosphorylates

Triacylglycerol lipase ( which is inactivated by phosphatase).

fatty acid from the Triacylglycerol lipase degrades one

triacylglycerol and turns it to Diacylglycerol (2 fatty acids).


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Diacylglycerol lipase (DAG lipase) degrades the second fatty

acid, and now we have monoacylglycerol (1 fatty acid).

ning Monoacylglycerol lipase (MAG lipase) degrades the remai

.fatty acid, so now we have a fatty acid and glycerol

are fatty acids triglyceridesdegradation of end product ofhe T

and glycerol .

. This is called lipolysis

etc part ii & lip met

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