Ch 4: Energy and Cellular Metabolism Energy as it relates to Biology Chemical reactions Enzymes and how they speed rxs Metabolism and metabolic pathways Catabolism (ATP production) Anabolism (Synthesis of biologically important molecules)

Energy in Biological Systems Review on your own!

Chemical Reactions Transfer energy or use energy to do work Substrates / reactants Products A + B C + D Bioenergetics: Study of energy flow through biol. systems Reaction rate = speed of reaction

Activation Energy Starts Reaction Fig 4-3 Reversible (most biol. rxs.) vs. irreversible reactions

Endergonic vs. Exergonic Reactions Coupling endergonic and exergoinic rxs Direct coupling vs. indirect coupling Which kind?

Enzymes are Proteins acting as Biological Catalysts 4 important characteristics of enzymes  chemical reaction rate by lowering activation energy are not changed themselves do not change nature of rx nor result are specific Fig 4-8

Active Site: Small region of the complex 3D structure is active (or binding) site. Enzymes bind to substrate Troponin I and T are structural components of cardiac muscle. They are released into the bloodstream with myocardial injury. They are highly specific for myocardial injury--more so than CK-MB--and help to exclude elevations of CK with skeletal muscle trauma. Troponins will begin to increase following MI within 3 to 12 hours, about the same time frame as CK-MB. However, the rate of rise for early infarction may not be as dramatic as for CK-MB. Troponins will remain elevated longer than CK--up to 5 to 9 days for troponin I and up to 2 weeks for troponin T. This makes troponins a superior marker for diagnosing myocardial infarction in the recent past--better than lactate dehydrogenase (LDH). However, this continued elevation has the disadvantage of making it more difficult to diagnose reinfarction or Old: Lock-and-key model / New: Induced-fit model Fig 2-16

Naming of Enzymes mostly suffix -ase first part gives info on function Not in book Naming of Enzymes mostly suffix -ase first part gives info on function Kinase Phosphatase Peptidase Dehydrogenase examples

Isozymes = different models of same enzyme (differ in 1 or few aa) Catalize same reaction under different conditions and in different tissues/organs Examples: Amylase LDH → importance in diagnostics (LDH) Lactate dehydrogenase  - Total LDH will begin to rise 2 to 5 days after an MI; the elevation can last 10 days. 140-280 U/L Normal Adult Range: 0 - 250 U/L Optimal Adult Reading: 125 Review Table 4-3

Enzyme Activity depends on proteolytic activation (for some) cofactors & coenzymes (for some) temperature pH other molecules interacting with enzyme

1) Proteolytic Activation Also Pepsinogen Pepsin Trypsinogen Trypsin

2) 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

6) Molecules interacting with enzyme cont. Competitive inhibitors: reversible binding to active site Fig 2-19 block active site Also possible: irreversible binding via covalent bonds, e.g.: Penicillin Tamoxifen

Reversible Reactions follow the Law of Mass Action Fig 4-9

Three Major Types of Enzymatic Reactions: Oxydation - Reduction reactions (transfer of ?) Hydrolysis - Dehydration reactions (breakdown & synthesis of ?) Addition-Subtraction-Exchange reactions

Metabolism Anabolism Catabolism   Catabolism (ATP production) Anabolism (Synthetic pathways) Anabolism Catabolism  

Metabolic pathways = network of linked reactions Metabolism definition: ___________ Metabolic pathways = network of linked reactions Cells regulate metabolic pathways via Control of enzyme concentration Modulator production (allosteric modulators, feedback inhibition, Fig 4-11) Different enzymes for reversible rxs, Fig 4-12) Compartmentation of enzymes ATP / ADP ratio

Catabolic Pathways: ATP-Production Amount of ATP produced reflects on usefulness of metabolic pathways: Aerobic pathways Anaerobic pathways Different biomolecules enter pathway at different points

Glycolysis From 1 glucose to 2 pyruvate molecules Main catabolic pathway of cytoplasm Does not require O2  part of _________ and ____________ catabolism Starts with phosphorylation (“Before doubling your money you first have to invest!”) Fig 4-13

Pyruvate has 2 Possible Fates Anaerobic catabolism: Pyruvate lactate Aerobic catabolism: Pyruvate Citric Acid Cycle

Citric Acid Cycle Other names ? Takes place in ? Energy Produced: 1 ATP 3 NADH 1 FADH2 Waste – 2 CO2 Fig. 4-16

Final step: Electron Transport System Chemiosmotic theory / oxydative phosphorylation Transfers energy from NADH and FADH2 to ATP (via e- donation and H+ transport) Mechanism: Energy released by movement of e- trough transport system is stored temporarily in H+ gradient NADH produces a maximum of 2.5 ATP FADH2 produces a maximum of 1.5 ATP 1 ATP formed per 3H+ shuttled through ATP Synthase Fig 4-17

Cellular Respiration Maximum potential yield for aerobic glucose metabolism: 30-32 ATP synthesized from ADP H2O is a byproduct

Synthetic Pathways Anabolic rxs synthesize large biomolecules Unit molecules Macromolecules nutrients & energy required Polysaccharides Lipids DNA Protein

Glycogen Synthesis Gluconeogenesis Made from glucose Stored in all cells but especially in Liver (keeps 4h glycogen reserve for between meals) Skeletal Muscle  muscle contraction Gluconeogenesis Glycolysis in reverse From glycerol, aa and lactate All cells can make G-6-P, only liver and Kidney can make glucose

Protein Synthesis Proteins are the key to cell function → necessary for all cell functions Protein synthesis is under nuclear direction  DNA specifies Proteins DNA mRNA Protein ? ?

How can only 4 bases in DNA encode > 20 different aa in protein? 1 letter word: 1 base = 1 aa  how many possibilities? 2 letter word: 2 bases = 1 aa how many possibilities? 3 letter word: 3 bases = 1 aa  how many possibilities? 3 letter words = base triplets or codons

Redundancy of Genetic Code 1 start codon (AUG = Met) 3 stop codons 60 other codons for 19 aa

Transcription DNA is transcribed into complementary mRNA by RNA Polymerase + nucleotides + Mg2+ ( = ?) + ? Gene = elementary unit of inheritance Compare to Fig. 4-25

Translation mRNA is translated into string of aa (= polypeptide) 2 important components ?? mRNA + ribosomes + tRNA meet in cytoplasm Anticodon pairs with mRNA codon  aa determined Amino acids are linked via ______________ bond. Fig 4-27

Protein Sorting Due to signal/targeting sequence Post – Translational protein modifications: Folding, cleavage, additions  glyco- , lipo- proteins Protein Sorting Due to signal/targeting sequence No targeting sequence  protein stays in cytoplasm Targeting sequence  protein destined for translocation into organelles or for export from cell

Transition vesicles to For “export proteins”: Signal sequence leads growing polypeptide chain across ER membrane into ER lumen Modifications in ER Transition vesicles to Golgi apparatus for further modifications Transport vesicles to cell membrane Compare to Fig 4-28

DNA Replication Semi- conservative DNA polymerase

the end Running problem: Tay-Sachs Disease