cho l5, l6 metabolisim 2nd nutri

8/3/2019 CHO L5, L6 Metabolisim 2nd Nutri

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Lecture 5

CARBOHYDRATES

CarbohydratesBioenergetics and Metabolism


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Lecture - 5

Metabolic Pathways:

Definition

Anabolism

Catabolism & Catabolic stages

Regulation of metabolism: Signals from within the cell

Communication between cells

Membrane receptor

Intracellular messenger systems


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Metabolism

Is the sum of all chemical changes

occurring in a cell, a tissue, or thebody.


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Metabolic pathways:

Definition:

It is formed of a sequence of enzymaticreactions where the product of an enzymatic

reaction becomes the substrate for the nextreaction; the successive products of thereactions known as metabolites or metabolicintermediates.


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Metabolic pathways

Metabolism is classified into:

Anabolism

and

Catabolism


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I- Anabolism

It includes all the biosyntheticpathways which are concerned withsynthesis of complex end products fromsimple precursors, for example,synthesis of glycogen, proteins andlipids from simple molecules.

Anabolic reactions require energywhich is supplied mainly by adenosinetriphosphate (ATP).


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II- Catabolism

It includes all degradative processeswhereby complex molecules, such asproteins, polysachharides, and lipids,are broken into a few simple molecules

, for example, CO2, NH3 and water.

Catabolism is classified into three mainstages:


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Stage I:

Hydrolysis of complex molecules:

Complex molecules are broken downinto their component building blocks.

For example, proteins are degraded toamino acids, polysaccharides tomonosaccharides, and triacylglycerolsto free fatty acids and glycerol.


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Stage II:

Conversion of building blocks to simpleintermediates:

The diverse building blocks are further

degraded to acetyl CoA and a fewother, simple molecules.

Some energy is captured as ATP.


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Stage III:

Oxidation of acetyl CoA: The tricarboxylic acid (TCA) cycle is the

final common pathway in the oxidation

of fuel molecules such as acetyl CoA. Large amounts of ATP are generated as

electrons flow from NADH and FADH2 to

oxygen via oxidative phosphorylation.


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Stage Three

Stage One Stage One

Carbohydrates Proteins Lipids

Monosaccharides Amino Acids Glycerol + Fatty Acids

Stage One

Acetyl-CoAOR Intermediates of Citric Acid Cycle

2 CO2 + ATP

Stage Two

KrebsCycle

ReducedCoenzyme

ETC

ATP + H2O


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Bioenergetics


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LOW AND HIGH ENERGYBONDS

When ATP is hydrolyzed to ADP + Pi,the energy released is about 7.3 Kcal/mole (7300 cal/mole).

Chemical bonds are mainly two typesas follows:

I- Low Energy Bonds

II- High Energy Bonds


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I- Low Energy Bonds

These are bonds that on hydrolysis

produce an amount of free energy lessthan 7 Kcal/mole and include most ofchemical bonds, for example:

1- Phosphate ester bondse.g.glucose -6- P or glucose -1- P.

2- Glycosidic bondsin

carbohydrates.3- Peptide bondsin proteins.


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II- High Energy Bonds

These are bonds which on hydrolysis produce an

amount of free energy more than 7 (7.3 - 14.8)Kcal/mole. They include the following:

P~ = ~P OH

O

OH

High Energy Phosphate Bonds :

1- Enol-Phosphate:

ex: 2-phospho enol pyruvate

COOH

C

CH2

O~ P

2- Carboxylic ~ Phosphate bonds:

ex: a) alpha-1,3-Bisphosphoglycerate

O

C O

CH OH

CH2 O P

P~


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ATP

ATP is a high energy compound.

It consists of adenosine (adenine + ribose) towhich three phosphate groups are attached.

If one phosphate is removed, adenosinediphosphate (ADP) is produced; if twophosphates are removed, adenosinemonophosphate (AMP) results.

The standard free energy of hydrolysis ofATP is approximately -7300 cal/mole for eachof the two terminal phosphate groups.


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Adenosine Triphosphate

(ATP)


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ATP ADP

P~

Creatine

Creatine

P~

P~

Oxidative Phosphorylation

MuscleContraction

Active transport

AnabolismNerve Impulses

Phosphorylationof compounds

Muscles

ATP-ADP Cycle


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Mechanism Of Collection Of

Energy:

Free energy liberated during thedegradation of foodstuffs is collectedin the form of high energy phosphate

bonds at 2 levels in metabolism.

At the substrate level and

At the respiratory chain level.


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A) Substrate Level Phosphorylation:A high-energy bond is formed in the substrate

while being oxidized. ATP is then generatedat the expense of this high-energy bond, asin the following reactions:

1,3-Biphosphoglycerate + ADP 3- phosphoglycerate + ATP

Phosphoglycerate Kinase

Phosphoenolpyruvate +ADP Enolpyruvate + ATPPyruvate Kinase

Succinyl-CoA +ADP + Pi Succinic Acid + ATPSuccinate thiokinase

B) Oxidative Phosphorylation:

CARBOHYDRA


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Electron Transport Chain

(ETC)

Lecture - 6

CARBOHYDRATES


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Lecture - 6

Electron Transport Chain: Overview

Components of ETC

Chemiosmotic Hypothesis

Synthesis of ATP (ATP Synthase)

Control of oxidation in ETC

Inhibitors of ETC

Uncouplers


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-Energy-rich compounds , such as carbohydrates, fats

and proteins are metabolized by a series of oxidation

reactions yielding CO2

and water.

-The metabolic intermediates of these reactions

donate electrons to specific coenzymes

nicotineamide adenine dinucleotide (NAD+) andflavin adenine dinucleotide (FAD) to form the

energy-rich reduced coenzymes, NADH and FADH2.

- These reduced coenzymes can, in turn, each donate

a pair of electrons to a specialized set of electron

carriers, collectively called the electron transport

chain.


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- An electrons are passed down the electron

transport chain, they lose much of their freeenergy.

-Part of this energy can be captured and storedby the production of ATPfrom ADP and

inorganic phosphate (Pi).

-This process is called oxidative

phosphorylation.


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Active acetate Kreb's Cycle Reduced Coenzymes + 2CO2

ETC

O

Oxidized Coenzymes+ H2O

EnergyADP + PiATP

Phosphorylation


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ELECTRON TRANSPORT CHAIN (ETC)RESPIRATORY CHAIN

ETC is formed of a series of electroncarriers, which catalyze the transfer ofelectrons from reduced coenzymes to

oxygen to form H20. Part of the energyreleased is utilized for synthesis ofhigh-energy phosphate bonds (i.e.

conversion of ADP + Pi to ATP).


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Components of ETC

The components of the ETC are located in the innermitochondrial membraneand is the final common

pathway by which electrons derived from different fuels ofthe body flow to oxygen.

Electron transport and ATP synthesis by oxidativephosphorylation proceed continuously in all tissues that

contain mitochondria.

Note:

- The inner mitochondrial membrane is impermeable tomost small ions, including H+, Na+, and K+, smallmolecules such as ATP, ADP, pyruvate, and othermetabolites important to mitochondrial function.

- Specialized carriers or transport systems are required tomove ions or molecules across this membrane.


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Components of ETC

It is formed offour complexes and 2mobile electron carrier (coenzymes Qand cytochrome c).


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Electron transport chain


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Organization of ETC

The inner mitochondrial membrane containsfive enzyme complexes, called I, II, II, IV,and V.

Complexes I to IV each contain part of theETC, whereas complex V catalyzes ATPsynthesis.

Each complex accepts or donates electrons torelatively mobile electron carriers, such ascoenzyme Q and cytochrome c.

Each carrier in the ETC can receive electrons

from an electron donor, and can consequentlydonate electrons to the next carrier in thechain.

The electrons combine with oxygen and

protons to form water.


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Structure of amitochondrion

showing the electrontransport chain andATP synthesizing

structures on theinner membrane


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The chemiosmotic hypothesis explainshow the free energy generated by thetransport of electrons by the electrontransport chain is used to produce ATP

from ADP + Pi. Electron transport is coupled to the

phosphorylation of ADP by the transport ofprotons (H+) across the inner

mitochondrial membrane from the matrixto the intermembrane space.

Chemiosmotic hypothesis of ATP synthesis


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1. Proton pump:

It is proved that the energy of electrontransport through the ETC is utilized bycomplex I, III and IV that act as protonpumps, for transfer of protons from the

matrix to the inter-membrane space. This process creates, across the inner

mitohondrial membrane, an electericalgradient (with more positive charges on the

outside of the membrane than on the inside)and a pH gradient (the outside of themembrane is at a lower pH than the inside).

The energy generated by this proton gradient

is sufficient to drive ATP synthesis.

Chemiosmotic hypothesis


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2. ATP synthase (complex V): This enzyme complex synthesizes ATP, using

the energy of the proton gradient generated bythe ETC.

After protons have been transferred from thematrix to the intermembrane space, theyreenter matrix by passing through a channel inthe ATP synthase complex, resulting in the

synthesis of ATP from ADP + Pi and, at thesame time, dissipating the pH and electericalgradient.



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ChemiosmoticHypothesis
http://e/First%20Sem%2007/Animation%20files/ETC-animation.swf


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Oligomycin: This drug binds to ATP synthase, closing the H+

channel, and preventing reentry of protons intothe mitochondrial matrix.

Because the pH and electerical gradients cannotbe dissipated, electron transport stops.

As electron transport and phosphorylation aretightly coupled, inhibition of phosphorylationinhibits oxidation.



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A supply of ADP is necessary for ATPsynthesis; a low concentration of ADPwill result in decreased production of

ATP. Since electron transport and ATP

synthesis are tightly coupled, electron

transport and thus oxidation of NADHand FADH2 will also be inhibited.

Control of Oxidation in ETC


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These compounds prevent the passage ofelectrons by binding to a component ofthe respiratory chain, blocking the

oxidation-reduction reaction. Therefore, all electron carriers before the

block are fully reduced and those after theblock are oxidized.

Because electron transport and oxidativephosphorylation are tightly coupled, ATPsynthesis is also inhibited.

Inhibitors of ETC


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Site-Specific inhibitors of electrontransport


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They act to dissociate oxidation in theETC from phosphorylation (ATPsynthesis) and energy released as heat.

Electron transport and phosphorylationcan be uncoupled by compounds thatincrease the permeability of the inner

mitochondrial membrane to protonse.g. 2,4-dinitrophenol.

Uncouplers of ETC


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NADH is produced in the cytosol during

oxidation of glucose by glycolysis. NADH cannot pass through the

mitochondrial membrane to reach the

ETC for its oxidation. Instead, two shuttles can function in

the transfer of hydrogen (ReducedEquivalent) from NADH in the cytosol

to mitochondria: Glycerophosphate Shuttle.

Malate - Aspartate Shuttle.

Oxidation Of Extra-Mitochondrial NADH

Malate Aspartate Shuttle


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Glycerophosphate Shuttle Malate-Aspartate Shuttle

cho l5, l6 metabolisim 2nd nutri

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