topic 6: energy and cellular metabolism

• metabolism: sum of all chemical reactions in the body

  1. anabolism: synthesis of organic molecules (endergonic reactions)

  2. catabolism: breakdown of organic molecules(exergonic reactions)

• Exergonic reactions release energy (spontaneous, negative ΔG), while endergonic reactions require energy input (non-spontaneous, positive ΔG)

control of chemical reactions

• each reaction involves breaking bonds of reactants and forming new bonds in products

• typically, free energy is released during the process

• reactants have hig energy state (low stability) and products have low energy state (high stability)

• energy of chemical reactions measured in calories

  • 1 calorie is amount of heat needed to increase temperature of 1 gram of water by 1 °C

• what determines the rate of chemical reactions?

  1. concentration of reactants - Law of mass action determines rate and direction of reaction

  2. activation energy - the amount of energy needed by reactants to initiate breaking of chemical bond; involves collision of reactants with other molecules

     

     **the greater the amount of activation energy, the slower the reaction

  3. temperature: increasing temeprature increases kinetic energy of molecules (rate of collision) thus increasing chance of acheiving activation energy

  4. catalyst (enzyme) - acts to decrease energy of activation for reaction by altering charge distribution of reactants

     • **these reactions are reversible

**Maintaining structure of enzyme is critical to its function

• binding and cataytic sites drift away when tertiery structure breaks down (by pH or temp)

  • increasing temp a little → sites become closer together → inc rate of rxn

  • increase temp too much → breaks down protein

Biochemistry (in body)

• enzymes - proteins that increase reaction rate but do not cause the reaction to occur, they’re not used up during reaction

  • enzymes control activites and thus function of cells

• enzymes increase rate of chemical eaction by lowering the activation energy

• each cell contains ~4000 enzymes, dozens can be involved in a single metabolic pathway

• substrates are the reactants in enzymatic reactions

• substrate binding to active site of proteins, which has conplementary shape to substrate

• formation of enzyme/substrate complez subject to same factors as receptor/ligand binding (affinity, specificity, competition, saturation)

• activity of enzyme can also be regulated by molecules that are neither substrate nor product of that reaction

  • isozymes - same enzyme can exist in different states which alter the direction the direction of the same reaction

    

  • cofactors - some enzymes require presence of inorganic elements (trace elements like fe, mg, zinc)

    • cofactors do not directly participate in reaction, but cause conformational change in enzyme that increases binding of substrate

  • coenzymes - organic molecules (vitamins) tha directly participate in the rxn, but they are not used up

Factors Affecting Enzymatic Reactions

1. change in [substrate] : hormones play role in the (ec. catecholamines)

2. temperature

3. change in [enzymes]: involves transcriptional & translational regulation triggered by metabolic demand

   • in most reactions [substrate] > [enzymes]

   • in most cells [enzymes] determines role of reaction

4. changes in enzymatic activity: quicker method of altering rate of rxn then changing [enzyme]

   • how?

   • hormones act to phosphorylate (covalent modulation) enzymes. generally this increases rate of reaction

   • in metabolic pathways product of one reaction may alter enzyme structures of another reaction in the pathway

     • can increase or decrease activity (allosteric modulation)

atp is the common currency of all rxns in the body

• Principle Functions of ATP

  1. energize synthesis of improtant cellular components

  2. energize muscle contractions

  3. synthesis of organic molecules used for structure and function

  4. energize active transport

  5. keep cells “excitable”, Na+/K+ pump (in terms of muscle and neurons)

• energy released from ATP by ATPase(enzyme)

  • ATP + water → ADP + Pi + 7,000 cals/mole

• ATP stores 12,000 cals/mole, however real function of ATP is to transfer energy

• energy stored in ATP (in the body) will sustain life for ~ 90 sec (without regeration)

• phosphorylation (PC) is a major storage depot for energy (13,000 cals/mole)

• catabolic breakdown of food substrates leads to synthesis of ATP

  • carbs fats anf proteins

Breakdown of Sugar (Glycolsis) (blood sugar taken in and broken down)

• consists of 10 step metabolic pathay, leading to synthesis of 2 pyruvate molecules and net production of 2 ATP molecules

• all reactions occur in cytosol and non require oxygen

• in step 5, the 6 carbon molecule cleaved into two 3 carbon molecules

• rate of pyruvate depends on avalability of oxygen

  1. if inadequate oxygen avalable (anaerobic): pyruvate converted to lactate

     

  2. if enough oxygen available: pyruvate enter matrix of mitochondria and is converted to acetyl - CoA

PFK IS THE LIMITING STEP IN GLYCOLSIS

Krebs Cycle is 8 step metabolic pathway

• results in the production of

• key is transfer of H to coenzymes (NAD+ + FAD), electrons can then be used in O/P to produce ATP

• primary rate-limiting enzyme in the Krebs cycle, also known as the citric acid cycle or TCA cycle, is isocitrate dehydrogenase

so at this point its 16 ATP but take away two so its 14 NET

• O/P occurs in inner membrane of mitochondria, results in transfer of electrons from NADH and FADH2 to oxygen to form H20

• energy is released as electrons passed along cytochromes

  

transfer electrons from cytosolic NADH into the mitochondria, allowing NADH to participate in oxidative phosphorylation (since NADH itself cannot cross the mitochondrial membrane)

• Malate-Aspartate Shuttle (Heart, Liver, Slow-Twitch Muscle)

• Glycerol-Phosphate Shuttle (Muscle, Brain, Fast-Twitch Fibers)

so efficient → only water as byproduct

• electrons going down a hill (ETC)

• higher energy to low energy states

Catabolic Breakdown of Fat (B - oxidation)

• triacylglycerol composed of 3 fatty acids bound to glycerol backbone

• accounts for 80% of stored energy in body

• adipocytes synthesize and store triacylglycerols,

  • when energy is needed → release FAs and glycyerol into bloodstream

• FAs metabolized only in the presence of oxygen

• must first be activated by linking CoA to end of FA (requires energy)

• activation occurs in cytoplasm, allows FA to be moves into mitochondrial matrix where CoA converted to acetyl-CoA

• each round of B - oxidation cleaves off 2 carbon unit, and cleaves away the acteyl-CoA, and coennzymes reduced

• acetyl-CoA enter Krebs cycle and is oxidized to 12 ATp molecules

• FADH2 and NADH enter electron transport chain

  • FADH2 yields 2 ATP molecules

  • NADH yeilds 3 ATP molecules

each round of B - oxidation produces 17 ATP molecules

• ex. Stearate is 18 carbon FA, B- oxidation produces:

  • 9 acetyl coAs (108 ATP)

  • 8 FADH2 (16 ATP)

  • 8NADH (24 ATP)

  • total 148 produces but 2 are used to activate FA → net = 146 ATP

the first step in catabolizing fatty acids is activation

• activation step only time when addition of CoA requires energy expenditure

• B oxidation proceeds as follows

C - C - C - C - C - C - C - C - C - C 4 cuts

• yields 5 acetyl COA units ( 5 × 12 ATPs ) = 60

• yields 4 NADH units (4 × 3ATPS) = 12

• yields 4 FADH2 units (4 × 2ATPs) = 8

• total = 80 - 2(activation) net = 78

Catabolic Breakdown of Proteins

• protesases cleave peptide bonds to free Amino acids

• First step is to remove nitrogen atoms by either transamination or oxidase deamination

• in oxidative deamination, the removed nitrogen found as ammonia (NH3)

• ammonia converted to less toxic urea in liver and then excreted in urine

• in transamination and oxidative deamination, AA’s are converted to keto acids which can be used as intermediates in krebs cycle or glycolysis to produce ATP

BCAA’s (branch chain AA) - cab be used as energy substrates (enter TCA cycle) or for gluconeogenesis, or for muscle protein synthesis

• isoleucine, leucine, valine