ThermodynamicThermodynamics lawss laws

The total energy of a system remains The total energy of a system remains constantconstantThe total entropi of a system must The total entropi of a system must increase if a process is to occur increase if a process is to occur spontaneously.spontaneously.

TerminologiTerminologi

BMRBMR Free energyFree energy Coupler-uncoupler reactionCoupler-uncoupler reaction HypertermiaHypertermia Febris Febris Endergonik-eksergonikEndergonik-eksergonik Endotermik-eksotermikEndotermik-eksotermik UCPUCP

Demam Demam : Suhu tubuh meningkat diatas : Suhu tubuh meningkat diatas normal. Suhu tubuh normal 36,5 normal. Suhu tubuh normal 36,5 – 37,2ºC.– 37,2ºC.HiperpireksiaHiperpireksia : > 42 ºC.: > 42 ºC.HipotermiaHipotermia : < 35 ºC.: < 35 ºC.

Etiologi Etiologi : - Kelainan otak: - Kelainan otak - Bahan toksik- Bahan toksik( Keduanya mempengaruhi ( Keduanya mempengaruhi pusat pengaturan tempeatur di pusat pengaturan tempeatur di hipotalamus / hipotalamus / set point )set point )

What is metabolismWhat is metabolism

Metabolism is the sum of all of the enzymes-Metabolism is the sum of all of the enzymes-catalyzed reactions that take place in cellscatalyzed reactions that take place in cells..

Can be viewed as having two contrasting Can be viewed as having two contrasting processes :processes :

* catabolism : * catabolism : energy yielding reactionsenergy yielding reactions in which in which

complex mol are broken down to small moleculecomplex mol are broken down to small molecule

* anabolism : * anabolism : energy requiring reactions in which energy requiring reactions in which simple precursor molecule are converted into simple precursor molecule are converted into

complex mol.complex mol.

Stages of metabolismStages of metabolism

Stage 1 : digestion giving monomeric Stage 1 : digestion giving monomeric units that are absorbed from the gut.units that are absorbed from the gut.

Stage 2 : conversion of the Stage 2 : conversion of the monomeric units into simple mol monomeric units into simple mol within cells such as amino acids, within cells such as amino acids, glucose and fatty acids.glucose and fatty acids.

Stage 3 : simple mol oxidized to CO2 Stage 3 : simple mol oxidized to CO2 and water. Most of ATP generated in and water. Most of ATP generated in this stage.this stage.

Role of Acetyl CoARole of Acetyl CoA

Acetyl CoAAcetyl CoA

polysaccharides

monosaccharides

lipids

fatty acids

proteins

amino acids

fatty acids

triglcerides andphospholipids

ketone bodies

citric acid cycle

CO2 + H2O + ATP

cholesterol

bile salts steroids

Energy yielding in Energy yielding in catabolismcatabolism

Catabolism of C-H, lipids, aa to a Catabolism of C-H, lipids, aa to a simpler end-product such as CO2, H2O simpler end-product such as CO2, H2O and amonia is accompanied by the and amonia is accompanied by the synthesis of ATPsynthesis of ATP..

ATP is utilized for various cellular ATP is utilized for various cellular functions such as :functions such as :

synthesis of protein,RNA,DNA for growth, adaptation and repair,synthesis of protein,RNA,DNA for growth, adaptation and repair, synthesis of fat and glycogen,synthesis of fat and glycogen, performance of mechanical work,performance of mechanical work, active ion transport, active ion transport, absorptions of nutrients against the gradient. absorptions of nutrients against the gradient.

Energy MetabolismEnergy Metabolism

Each large macromolecule is broken Each large macromolecule is broken down into something smaller.down into something smaller.

Carbohydrates Carbohydrates Simple sugarsSimple sugars FatsFats Fatty acids and glycerolFatty acids and glycerol ProteinsProteins Amino acidsAmino acids

Each step in their breakdown must be a Each step in their breakdown must be a carefully controlled process.carefully controlled process.ATPATP is used is used as the basic energy transfer unit.as the basic energy transfer unit.

ATPATP ATPATP adenosine triphosphateadenosine triphosphate a nucleotide composed of three basic units.a nucleotide composed of three basic units.

adenine

phosphate chain

ribose

CH2 O

OH OH

N

NN

N

NH2

OPOPOPO -

O

O-

O

O-

O

O-

O-

O

P

O-P

O

P

O-O-

ATP and ADPATP and ADP

CH 2 O

OH OH

N

NN

N

NH 2

OPO

O O

O-

ADP

CH 2 O

OH OH

N

NN

N

NH 2

OPOOO-O

O-

ATP

It takes energyto put on thethird phosphate.

Energy isreleased whenit is removed.

ADP - ATP conversions actas a major method oftransferringenergy.

O-

O

P

O-P

O

P

O-O-

ATP and ADPATP and ADP

CH 2 O

OH OH

N

NN

N

NH 2

OPO

O O

O-

ADP

CH 2 O

OH OH

N

NN

N

NH 2

OPOOO-O

O-

ATP

It takes energyto put on thethird phosphate.

Energy isreleased whenit is removed.

ADP - ATP conversions actas a major method oftransferringenergy.

Energy, ATP and theEnergy, ATP and theMovement of PhosphateMovement of Phosphate

ATP

ADP

ADP

phosphoenolpyruvatephosphoenolpyruvate

1,3-diphosphoglycerate1,3-diphosphoglycerate

creatine phosphatecreatine phosphate

glucose-1-phosphateglucose-1-phosphate

fructose-6-phosphatefructose-6-phosphate

glucose-6-phosphateglucose-6-phosphate

P

En

erg

y

P

P

P

P

P

MitochondriaMitochondria ““Powerhouse” of the cell.Powerhouse” of the cell.

Innermembrane

Cristae

0.2-0.8 m

Outermembrane

Matrix

Intermembranespace

MitochondriaMitochondria

Outer membrane Outer membrane -- Mostly phospholipids and cholesterol.Mostly phospholipids and cholesterol. Contains transport protein that forms pores.Contains transport protein that forms pores. Very permeable.Very permeable. Inner membrane -Inner membrane - Highly folded structures known as Highly folded structures known as cristaecristae.. Inner space is called the Inner space is called the matrixmatrix.. Different structure compared to outer Different structure compared to outer membrane - not permeable.membrane - not permeable. Contains three types of proteins.Contains three types of proteins.

Inner Membrane ProteinsInner Membrane Proteins Transport Transport -- Used to move materials across inner Used to move materials across inner

membrane.membrane.

Respiratory chain -Respiratory chain - Complexes that are responsible for production Complexes that are responsible for production

of ATP from energy sources. Requires oxygen.of ATP from energy sources. Requires oxygen.

ATP synthase -ATP synthase - Used for the phosphorylation of ADP.Used for the phosphorylation of ADP.

All work together to produce energy in cell.All work together to produce energy in cell.

Where Reactions OccurWhere Reactions Occur

Synthesis occurs in the cytoplasm -Synthesis occurs in the cytoplasm - glycolysisglycolysis production of fatty acids and amino acidsproduction of fatty acids and amino acids

Oxidation occurs in the mitochondria -Oxidation occurs in the mitochondria - citric acid cyclecitric acid cycle fatty acid oxidationfatty acid oxidation oxidation of amino acidsoxidation of amino acids

This makes the various reactions easier to control This makes the various reactions easier to control because they occur in different places.because they occur in different places.

Oxidative PhosphorylationOxidative Phosphorylation

Much of the energy from metabolism Much of the energy from metabolism comes comes from this process.from this process.

NADH and FADHNADH and FADH22 are both used to produce additional ATP are both used to produce additional ATP when they are oxidized.when they are oxidized.

NADHNADHnicotinamide adenine dinucleotidenicotinamide adenine dinucleotide

FADHFADH22 flavin adenine dinucleotideflavin adenine dinucleotide

The oxidation relies on the flow of electrons using a The oxidation relies on the flow of electrons using a complex structure in the mitochondria. complex structure in the mitochondria.

Electron Transport ChainElectron Transport Chain

CoQ

Cyt bFP Fe-S

Cyt c1 Cyt cCyt a,a3Fe-S

NADH + H+ FADH2

4 H+ + 4 e- + O2

2 H2OFP flavoproteinFe-S iron-sulfur proteinCoQ coenzyme QCyt cytochromes. Structurally related proteins

that each contain iron

inner membrane space of mitochondria

inner membrane

Components of theComponents of theElectron Transport ChainElectron Transport Chain

cytochrome c

flavoprotein

Electron Transport ChainElectron Transport Chain This portion of the process is responsible This portion of the process is responsible

for the oxidation of NADH to NADfor the oxidation of NADH to NAD+ + (FADH(FADH22 as well).as well).

Results in HResults in H++ being built up in the being built up in the intermembrane space of the mitochondria.intermembrane space of the mitochondria.

This difference in HThis difference in H++ is what drives the is what drives the second portion of the system.second portion of the system.

Note - This phase requires oxygen!Note - This phase requires oxygen!

ATP Synthase andATP Synthase andthe Fthe F11 Complex Complex

Inner mitochondrial membrane

Outer mitochondrial membrane

H+ H+

H+

H+

H+H+H+

H+H+

H+

H+

H+ H+

H+

H+

ADP + Pi ATP

Electron Transport

Chain

Electron Transport

Chain

F1-ATPasecomplex

F1-ATPasecomplex

ATP Synthase andATP Synthase andthe Fthe F11 Complex Complex

In this step, the H+ concentration difference between the mitochondrial matrix and the intermembrane space is what provides the energy to produce ATP .

Steps consist of

HH++ Transport Transport movement of H+

FF11 Event Event production of ATP

ATP Produced per GlucoseATP Produced per Glucose Glycolysis:Glycolysis: 2 ATP2 ATP 2 ATP 2 ATP 2 NADH2 NADH 2.5 ATP/NADH2.5 ATP/NADH 5 ATP* 5 ATP*

Citric Acid Cycle:Citric Acid Cycle: 2 GTP2 GTP 1 ATP/GTP1 ATP/GTP 2 ATP 2 ATP 6 NADH6 NADH 2.5 ATP/NADH2.5 ATP/NADH 15 ATP15 ATP 2 FADH2 FADH22 1.5 ATP/FADH1.5 ATP/FADH22 3 3

ATPATP 32 32

ATPATP

* 3 ATP in muscle and brain.30 ATP / glucose

Energy YieldEnergy Yield30 - 32 ATP / glucose30 - 32 ATP / glucoseGlycolysis

Mitochondria

Glucose PyruvateGlucose Pyruvate

Oxidativephosphorylation

Oxidativephosphorylation

6 NADH+

2 FADH2

6 NADH+

2 FADH2 2 NADH2 NADH2 NADH2 NADH

2 ATP2 ATP 2 ATP2 ATP26-28 ATP26-28 ATP

Acetyl CoAAcetyl CoA

2 GTP2 GTP

Control of theControl of theCitric Acid CycleCitric Acid Cycle

Several routes for controlling the cycleSeveral routes for controlling the cycle..

Insufficient oxygenInsufficient oxygen..

Reduced energy demand causes a build up of ATP, Reduced energy demand causes a build up of ATP, NADH inhibitsNADH inhibits- -

Pyruvate to acetyl CoA conversionPyruvate to acetyl CoA conversion..Acetyl CoA production of citrate (ATP only)Acetyl CoA production of citrate (ATP only)..Some intermediate steps in the cycleSome intermediate steps in the cycle..

Excess ADP will stimulate many of these same Excess ADP will stimulate many of these same steps to make things go fastersteps to make things go faster..

Use of Amino AcidsUse of Amino Acidsand Fatty Acidsand Fatty Acids

Fats and protein can alsobe used by the bodyas a source of energy.

Not as easily used as carbohydrates.

Liver

glycogen

glucose-6-P

pyruvate

Liver

glycogen

glucose-6-P

pyruvate

Amino Acids

or

Fatty Acids

Amino Acids

or

Fatty Acids