Ch 4:Ch 4: Cellular Metabolism - P Cellular Metabolism - Part 2art 2Ch 4:Ch 4: Cellular Metabolism - P Cellular Metabolism - Part 2art 2

Energy as it relates to BiologyEnergy as it relates to Biology

EnzymesEnzymes

MetabolismMetabolism Catabolism (ATP production)Catabolism (ATP production)

Glycolysis and the TCA CycleGlycolysis and the TCA Cycle Anabolism (Synthetic pathways)Anabolism (Synthetic pathways)

Protein SynthesisProtein Synthesis

MetabolismMetabolism

Definition = “All chemical reactions that take Definition = “All chemical reactions that take place within an organism.”place within an organism.”

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

Basic feature: coupling of exergonicBasic feature: coupling of exergonic rxs with endergonic rxs. rxs with endergonic rxs. (direct vs. indirect coupling)(direct vs. indirect coupling)

Review:Review: Energy = capacity to do workEnergy = capacity to do work

Usually from ATPUsually from ATP Enzymes = biological catalystEnzymes = biological catalyst

Lower activation energyLower activation energy Return to original stateReturn to original state Opportunity for controlOpportunity for control

Metabolism Metabolism p 101p 101

Anabolism Synthesis

Energy transferred commonly measured in calories: 1 cal = 1 g of H2O by 1° C

1 Kcal = temp. of 1L H2O by 1o C. = Calorie (capital C)

Energy released in catabolic reactions is trapped in Energy released in catabolic reactions is trapped in 1) Phosphate bonds1) Phosphate bonds2) Electrons2) Electrons

Catabolism Energy

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

Circular pathway

Branched pathway

Intermediates

Control of Metabolic PathwaysControl of Metabolic Pathways

1.1. Enzyme concentration Enzyme concentration (already (already covered)covered)

2.2. Enzyme modulators Enzyme modulators - Feedback- or end product - Feedback- or end product inhibitioninhibition- Hormones- Hormones- Other signaling molecules- Other signaling molecules

3.3. Different enzymes for reversible Different enzymes for reversible reactionsreactions

4.4. Enzyme isolationEnzyme isolation

5.5. Energy availability (ratio of ADP Energy availability (ratio of ADP to ATP)to ATP)

(Chapter 6)

Catabolic Pathways: Catabolic Pathways: ATP-Regeneration-Regeneration

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 (6 carbons) to 2 From 1 glucose (6 carbons) to 2 pyruvate (3 carbons) moleculespyruvate (3 carbons) molecules

Main catabolic pathway of cytoplasmMain catabolic pathway of cytoplasm

Does not require ODoes not require O2 2 common for common for (an)aerobic catabolism(an)aerobic catabolism

Starts with phosphorylation of Starts with phosphorylation of Glucose to Glucose 6-PGlucose to Glucose 6-P

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

Net gain?

The Steps of The Steps of GlycolysisGlycolysis

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

Electron transport System

NADH

NADHNADH

FADH2

Energy Yield of Krebs Cycle

See Fig. 4-24

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

Chemiosmotic theory / oxidative 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 Energy released by movement of emovement of e-- through transport system through transport system is stored temporarily in His stored temporarily 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 4-25

Cellular Cellular RespirationRespiration

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

H2O is a byproduct

Summary of CHO catabolism

Protein Catabolism??Protein Catabolism?? ProteasesProteases PeptidasesPeptidases Deamination (removal Deamination (removal

of the NHof the NH33)) NHNH3 3 becomes ureabecomes urea

Pyruvate, Acetyl CoA, Pyruvate, Acetyl CoA, TCA intermediates are TCA intermediates are left.left.

Lipid Catabolism??Lipid Catabolism??

LipolysisLipolysis Lipases break lipids Lipases break lipids

into glycerol (3-C)into glycerol (3-C)

Glycerol enters the Glycerol enters the glycolytic pathwayglycolytic pathway Called Called ββ-oxidation-oxidation

Synthetic PathwaysSynthetic Pathways

Unit molecules Macromolecules

PolysaccharidesLipidsDNA

Protein

nutrients & energy required

Anabolic reactions synthesize large Anabolic reactions synthesize large biomoleculesbiomolecules

GlucoseAmino Acids

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 contraction muscle 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 and All cells can make G-6-P, only liver and Kidney can make glucoseKidney can make glucose

Proteins are necessary for cell functionsProteins are necessary for 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? ?

1 start codon1 start codon

3 stop codon3 stop codon

60 other codons for 60 other codons for 19 aa19 aa

Redundancy of Genetic Code (p 115)

A combination of three bases forms a codon

TranscriptionTranscription

DNADNA is transcribed into is transcribed into complementary complementary mRNAmRNA

byRNA PolymeraseRNA Polymerase

+ nucleotides+ Mg2+

+ ATP

Gene = elementary unit of inheritance

Compare to Fig. 4-33

Protein synthesis Protein synthesis fig 4-27fig 4-27

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 peptide bond.

2 important components ??

Fig 4-34

Primary Structure

Protein SortingProtein Sorting No signal sequence No signal sequence protein stays in cellprotein stays in cell

Signal sequence Signal sequence protein destined for translocation protein destined for translocation into organelles or into organelles or for for exportexport

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

Modifications in ERModifications in ER

Transition vesicles toTransition vesicles to

Golgi apparatus for further Golgi apparatus for further modificationsmodifications

Transport vesicles to cell Transport vesicles to cell membranemembrane

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

DNA Replication DNA Replication

Semi- Semi- conservativeconservative

DNA DNA polymerasepolymerase