Ch 4: Energy and Cellular Ch 4: Energy and Cellular MetabolismMetabolism

Ch 4: Energy and Cellular Ch 4: Energy and Cellular MetabolismMetabolism

EnergyEnergy as it relates to Biology as it relates to Biology

Chemical reactionsChemical reactions

EnzymesEnzymes and how they speed rxs

MetabolismMetabolism and metabolic pathways and metabolic pathways CatabolismCatabolism (ATP production) (ATP production) AnabolismAnabolism ( (Synthesis of biologically

important molecules))

Energy in Biological SystemsEnergy in Biological Systems

Review on your own!

Chemical ReactionsChemical Reactions

1.1. Transfer energyTransfer energy

2.2. or use energy to do workor use energy to do work

Substrates / reactants Products

BioenergeticsBioenergetics: Study of energy flow through biol. systems

Reaction rate = speed of reaction

A + B A + B C + DC + D

Activation Energy Starts ReactionActivation Energy Starts Reaction

Reversible (most biol. rxs.) vs. Reversible (most biol. rxs.) vs. irreversible reactionsirreversible reactions

Fig 4-3

Endergonic vs. Exergonic ReactionsEndergonic vs. Exergonic Reactions

CouplingCoupling endergonic endergonic and exergoinic rxsand exergoinic rxs

DDirect coupling vs. irect coupling vs. indirect couplingindirect coupling

Which kind?

Enzymes are Proteins acting as Enzymes are Proteins acting as Biological CatalystsBiological Catalysts

1.1. chemical reaction rate by lowering chemical reaction rate by lowering activation energyactivation energy

2.2. are are not changed themselves themselves

3.3. do not change nature of rx nor resultdo not change nature of rx nor result

4.4. are specificare specific

4 important characteristics of enzymes

Fig 4-8

Enzymes lower activation energy:Enzymes lower activation energy:All chemical reactions in body must be conducted at body temp.!!

How do enzymes lower activation energy ?

Enzymes bind to reactant molecules and Enzymes bind to reactant molecules and bring them together in best position for rx.bring them together in best position for rx.

Small region of the complex Small region of the complex 3D structure is active (or 3D structure is active (or

binding) site.binding) site.

Enzymes bind to substrateEnzymes bind to substrate

Active Site:Active Site:

Old: Lock-and-key model / New: Induced-fit modelFig 2-16

Enzyme-substrate interaction: Enzyme-substrate interaction: The old and the new modelThe old and the new model

Naming of EnzymesNaming of Enzymes

KinaseKinase

PhosphatasePhosphatase

PeptidasePeptidase

DehydrogenaseDehydrogenase

mostly suffix mostly suffix -ase-asefirst part gives info on functionfirst part gives info on function

examples

Not in book

IsozymesIsozymes == different models of same different models of same enzyme (differ in 1 or few aa)enzyme (differ in 1 or few aa)

ExamplesExamples::

1.1. AmylaseAmylase

2.2. LDH → LDH → importance in diagnostics

Catalize same reaction under Catalize same reaction under different conditions and in different conditions and in

different tissues/organsdifferent tissues/organs

Review Table 4-3

Enzyme Activity Enzyme Activity depends on depends on

1. proteolytic activation (for some)(for some)

2. cofactors & coenzymes (for some)(for some)

3. temperature

4. pH

5. other molecules interacting with enzymeinteracting with enzyme

1) Proteolytic 1) Proteolytic Activation Activation

Also 1. Pepsinogen Pepsin2. Trypsinogen Trypsin

2) Cofactors & Coenzymes2) Cofactors & Coenzymes

structure:___________ molecules

(e.g. ?)

function:conformational change

of active site

structure:Organic molecules (vitamin derivatives, FADH2 ....)

function:act as receptors & carriers for atoms or functional groups that are removed from substrate

5) Molecules interacting with enzyme: 5) Molecules interacting with enzyme:

Allosteric Modulators bind to enzyme away bind to enzyme away from active site changing shape of active site for better or for from active site changing shape of active site for better or for worseworse

Allosteric Activator

Allosteric Inhibitor

Fig 2-20

5) Molecules interacting with enzyme cont.5) Molecules interacting with enzyme cont.

Competitive inhibitorsCompetitive inhibitors::

reversible binding to reversible binding to active site active site

block active siteblock active site

Also possible: irreversible binding via covalent bonds, e.g.:• Penicillin • Cyanide

Fig 2-19Fig 2-19

Reversible Reactions follow the Reversible Reactions follow the Law of Mass ActionLaw of Mass Action

Fig 4-9

Three Major Types of Enzymatic Three Major Types of Enzymatic Reactions:Reactions:

1. Oxydation - Reduction reactions(transfer of ?)(transfer of ?)

2.2. Hydrolysis - Hydrolysis - Dehydration reactions(breakdown & synthesis of ?)(breakdown & synthesis of ?)

3.3. Addition-Subtraction-Exchange Addition-Subtraction-Exchange reactionsreactions

?

MetabolismMetabolism

Catabolism Anabolism

Metabolism definition: ___________Metabolism definition: ___________

Metabolic pathways = network of Metabolic pathways = network of linked reactions linked reactions

Cells regulate metabolic pathways viaCells regulate metabolic pathways via1. Control of enzyme concentration2. Modulator production (allosteric

modulators, feedback inhibition, Fig 4-11)

3. Different enzymes for reversible rxs, Fig 4-12)

4. Compartmentation of enzymes

5. ATP / ADP ratio

Metabolic pathways: Network of Metabolic pathways: Network of interconnected chemical reactionsinterconnected chemical reactionsLinear pathway

Circular pathway

Branched pathway

Intermediates

= end product inhibitionSpecial case:

Fig 4-11

Catabolic Pathways: Catabolic Pathways: ATP-Production-Production

Amount of ATP produced reflects on usefulness of metabolic pathways:

Aerobic pathways

Anaerobic pathways

Different biomolecules enter pathway at different points

ATP Cycle

ATP = Energy Carrier of Cell ATP = Energy Carrier of Cell (not very useful (not very useful for energy storage) for energy storage)

ATP : ADP ratio determines status of ATP synthesis reactions

GlycolysisGlycolysis From 1 glucose to 2 From 1 glucose to 2

pyruvate moleculespyruvate molecules

Main catabolic pathway of Main catabolic pathway of cytoplasmcytoplasm

Does not require ODoes not require O2 2 part part of _________ and of _________ and ____________ catabolism____________ catabolism

Starts with Starts with phosphorylation phosphorylation (“Before (“Before doubling your money you first doubling your money you first have to invest!”)have to invest!”)

Fig 4-13

Anaerobic catabolism: Pyruvate

lactate

Aerobic catabolism: Pyruvate

Citric Acid Cycle

Pyruvate has 2 Possible Fates Pyruvate has 2 Possible Fates

Citric Acid CycleCitric Acid Cycle

Other names ?Other names ?

Takes place in ?Takes place in ?

Energy Produced:Energy Produced:1 ATP1 ATP3 NADH 3 NADH 1 FADH1 FADH22

Waste – 2 COWaste – 2 CO22

Fig. 4-16

NADH

NADHNADH

FADH2

Energy Yield of Krebs Cycle

Compare to Fig. 4-16

Final step:Final step: Electron Transport System Electron Transport System

Chemiosmotic theory / oxydative phosphorylation

Transfers energy from NADH and FADHTransfers energy from NADH and FADH22 to ATP to ATP (via e(via e- - donation and Hdonation and H++ transport) transport)

Mechanism:Mechanism: Energy released by movement Energy released by movement of eof e-- trough transport system is stored trough transport system is stored temporarily in Htemporarily in H++ gradient gradient

NADH produces a maximum of 2.5 ATP NADH produces a maximum of 2.5 ATP FADHFADH22 produces a maximum of 1.5 ATP produces a maximum of 1.5 ATP

1 ATP formed per 3H+ shuttled through ATP Synthase

Fig 4-17

Cellular Cellular RespirationRespiration

Maximum potential yield for aerobic glucose metabolism: 30-32 ATP synthesized from ADP

H2O is a byproduct

Synthetic PathwaysSynthetic Pathways

Unit molecules Macromolecules

PolysaccharidesLipidsDNA

Protein

nutrients & energy required

Anabolic rxs synthesize large biomoleculesAnabolic rxs synthesize large biomolecules

Glycogen SynthesisGlycogen SynthesisMade from glucoseMade from glucose

Stored in all cells but especially inStored in all cells but especially in Liver Liver (keeps 4h glycogen reserve for between meals)(keeps 4h glycogen reserve for between meals)

Skeletal Muscle Skeletal Muscle muscle contractionmuscle contraction

GluconeogenesisGluconeogenesisGlycolysis in reverse Glycolysis in reverse

From glycerol, aa and lactateFrom glycerol, aa and lactate

All cells can make G-6-P, only liver All cells can make G-6-P, only liver and Kidney can make glucoseand Kidney can make glucose

Proteins are the key to cell function → Proteins are the key to cell function → necessary for all cell functionsnecessary for all cell functions

Protein synthesis is under nuclear direction Protein synthesis is under nuclear direction DNA specifies ProteinsDNA specifies Proteins

Protein SynthesisProtein Synthesis

DNA DNA mRNA mRNA Protein Protein? ?

How can only 4 bases in DNA How can only 4 bases in DNA encode > 20 different aa in protein?encode > 20 different aa in protein?

1 letter word: 1 base = 1 aa 1 letter word: 1 base = 1 aa how many possibilitieshow many possibilities??

2 letter word: 2 bases = 1 aa2 letter word: 2 bases = 1 aa how many possibilitieshow many possibilities??

3 letter word:3 letter word: 3 bases = 1 aa 3 bases = 1 aa how many possibilitieshow many possibilities??

3 letter words3 letter words = = base triplets base triplets or or codonscodons

1 start codon 1 start codon (AUG = Met)(AUG = Met)

3 stop codons3 stop codons

60 other 60 other codons for codons for 19 aa19 aa

Redundancy of Genetic Code

TranscriptionTranscription

DNADNA is transcribed into is transcribed into complementary complementary mRNAmRNA

byRNA PolymeraseRNA Polymerase

+ nucleotides+ Mg2+ ( = ?)

+ ?

Gene = elementary unit of inheritance

Compare to Fig. 4-25 and review Fig 4-26

TranslationTranslationmRNA is translated into string of aa mRNA is translated into string of aa (= polypeptide)(= polypeptide)

mRNA + ribosomes + tRNA meet in cytoplasm

Anticodon pairs with mRNA codon aa determined

Amino acids are linked via

______________ bond.

2 important components ??

Fig 4-27

Protein SortingProtein Sorting

Due to signal/targeting sequence Due to signal/targeting sequence No targeting sequence No targeting sequence protein stays in cytoplasmprotein stays in cytoplasm

Targeting sequence Targeting sequence protein destined for protein destined for translocation into organelles or for export from celltranslocation into organelles or for export from cell

Post – Translational protein modifications: Folding, cleavage, additions glyco- , lipo- proteins

For “export proteins”: Signal sequence For “export proteins”: Signal sequence leads growing polypeptide chain across ER leads growing polypeptide chain across ER membrane into ER lumenmembrane into ER lumen

Modifications in ERModifications in ER

Transition vesicles toTransition vesicles to

Golgi apparatus for further modificationsGolgi apparatus for further modifications

Transport vesicles to cell membraneTransport vesicles to cell membrane Compare to Fig 4-28

DNA Replication DNA Replication

Semi- Semi- conservativeconservative

DNA DNA polymerasepolymerase

Running problem: Tay-Sachs Disease