WEEK 5 - BIOENERGETICS AND BIOLOGICAL OXIDATION.pdf

BIOCHEMISTRY Week 5: Bioenergetics and Biological Oxidation Prepared by: Arriane Lecturer: Farr Krizha I. Tangkusan, RN, MD Date: September 6, 2024 BIOENERGETICS COUPLING...

BIOCHEMISTRY Week 5: Bioenergetics and Biological Oxidation Prepared by: Arriane Lecturer: Farr Krizha I. Tangkusan, RN, MD Date: September 6, 2024 BIOENERGETICS COUPLING The transfer and utilization of energy in biologic systems  ΔG of two consecutive reactions are additive  All ΔGs of a pathway are additive: DEFINITION OF TERMS o A large negative ΔG reaction will couple with a smaller Change in Enthalpy (ΔH): positive ΔG reaction to yield an overall negative reaction  Measure of change in heat content of the reactants and products o Endergonic processes proceed by coupling to exergonic  Measured in joules (J) processes Change in Entropy (ΔS)  Measure of the change in randomness or disorder of the reactants and products  Measured in joules/Kelvin (J/K) Change in Free Energy (ΔG)  Portion of the total energy change in a system that is available for doing work—that is, the useful energy  Also known as the chemical potential  Approaches zero as reaction proceeds to equilibrium LAWS OF THERMODYNAMICS 1st Law: “The total energy of a system, including its surroundings, remains Notes: constant.” Point AB: Exergonic process, thus releases free energy Point CD: Endergonic process, thus energy is required In living systems, chemical energy may be transformed into heat or into electrical, radiant, or mechanical energy.  Endergonic process can’t exist alone, and needs to work with exergonic process (Coupling reaction) 2nd Law: “The total entropy of the system must increase if a process is to occur spontaneously.” Entropy, ΔS – extent of disorderliness/randomness of the system; becomes maximum as equilibrium is approached. FREE ENERGY Free energy, ΔG – portion of the total energy in the system that is available for work. ΔG = ΔH – TΔS ADENOSINE TRIPHOSPHATE (ATP)  Adenosine molecule to which three phosphate groups are attached  Acts as the energy currency of the cell, transferring free energy derived from substances of higher energy potential to those of lower energy potential  Hydrolysis of ATP yields a large – ΔGO  ATP → ADP + Pi (ΔGO = –7300 cal/mol) Mnemonics: ABCD Anabolic – Building Catabolic – Destroying BIOCHEMISTRY Prepared by: ARRIANE Date: SEPTEMBER 6, 2024 1 BIOCHEMISTRY Week 5: Bioenergetics and Biological Oxidation Prepared by: Arriane Lecturer: Farr Krizha I. Tangkusan, RN, MD Date: September 6, 2024 Notes: ATP as basis  ATP acts as donor; donates energy (phosphate) to create compounds below o Glucose-1-phosphate, PPi, Fructose-6-phosphate, etc.  ADP acts as acceptor; accepts phosphate from compounds above to form ATP o Phosphoenolpyruvate, Carbamoyl phosphate, etc. SUMMARY  Biologic systems use chemical energy to power living processes  Exergonic reactions take place spontaneously with loss of free energy (ΔG is negative). Endergonic reactions require the gain of free energy (ΔG is positive) and occur only when coupled to exergonic reactions.  ATP acts as the “energy currency” of the cell, transferring free energy derived from substances of higher energy potential to those of lower energy potential. BIOCHEMISTRY Prepared by: ARRIANE Date: SEPTEMBER 6, 2024 2 BIOCHEMISTRY Week 5: Bioenergetics and Biological Oxidation Prepared by: Arriane Lecturer: Farr Krizha I. Tangkusan, RN, MD Date: September 6, 2024 BIOLOGICAL OXIDATION OXIDOREDUCTASES Enzymes involved in oxidation-reduction reactions OXIDATION Removal of electrons Types: 1. Oxidases Mnemonics: LEORA 2. Dehydrogenases 3. Hydroperoxidases Loss of Electrons for Oxidation 4. Oxygenases Molecule  Reducing Agent Oxidases REDUCTION  Use O2 (or ½ O2) as H+ acceptor Gain of electrons  If 1 oxygen atom is the H+ acceptor, the product is water  If 2 oxygen atoms accepted the H+, the product is hydrogen Mnemonics: GEROA peroxide Gain of Electrons for Reduction Molecule  Oxidizing Agent COUPLED REACTIONS (REDOX/OXIDATION-REDUCTION)  Redox – Free energy (energy available in the system that can be used for bond breaking or bond formation) change is proportionate to the tendency of the reactants to donate or accept electrons; can be directly expressed as redox potential. o Examples include cellular respiration, detoxification of substances Examples:  Cytochrome oxidase (“Cytochrome aa3”) o Hemoprotein – part of the respiratory chain o Transfer electrons from oxidized substrates to oxygen to form water o Last step of the Electron Transport Chain (ETC)  Flavoprotein oxidases – FMN/FAD as prothetic groups o L-amino acid oxidase – oxidative deamination of L-amino acids o Xanthine oxidase – purine bases  uric acid o Aldehyde dehydrogenase – acts on aldehydes and alcohols Notes: FMN – Flavin mononucleotide FAD – Flavin adenine dinucleotide Both of these prosthetic groups are derived from Riboflavin (Vitamin B2); covalently bonded to enzymes Notes:  If redox potential is more negative, there is a higher tendency for that substance to become reduced; these produces stronger Dehydrogenases oxidizing agent  Cannot use O2 as H+ acceptor  If redox potential is more positive, the substance has a higher  Transfer of hydrogen from one substrate to another by utilizing tendency to become oxidized; these produces stronger reducing NAD+ as a coenzyme (i.e., lactate dehydrogenase) agent o Coenzyme lactate dehydrogenase is important for the conversion of pyruvate to lactate and vice versa Example: (reversible reaction) Pyruvate/Lactate (Reversible reaction) o The NADH used to reduced pyruvate to lactate, becomes NAD Pyruvate  Lactate: Redox potential should be -0.19 o If lactate is oxidized back to pyruvate, NAD accepts Lactate  Pyruvate: Redox potential should be +0.19 hydrogen atom to become NADH  Transfer of electrons from substrate to oxygen in the respiratory chain BIOCHEMISTRY Prepared by: ARRIANE Date: SEPTEMBER 6, 2024 3 BIOCHEMISTRY Week 5: Bioenergetics and Biological Oxidation Prepared by: Arriane Lecturer: Farr Krizha I. Tangkusan, RN, MD Date: September 6, 2024 Hydroxyperoxidases  Use H2O2 as substrate  protection against reactive oxygen species (ROS)  If a substrate is oxidized, it loses 2 hydrogen atoms and 2 electrons. 1 hydrogen atom and 2 electrons are accepted by FAD+ to form FADH, while the remaining 1 hydrogen atom is released. NAD+ and NADP+  Niacin (Vitamin B3) derived coenzymes Catalases  Hemoprotein with 4 heme groups  Action: Breakdown H2O2 to water and oxygen o Way to rapidly eliminate H2O2 produced intracellularly  Can also act as a peroxidase  Nicotinamide adenine dinucleotide (NAD+)-linked  Found in peroxisomes dehydrogenases: o Oxidative pathways of metabolism (i.e., glycolysis, Kreb’s cycle) Oxygenases o NADH  enter respiratory chain to form ATP  Catalyze direct transfer and incorporation of O2 into a substrate molecule  Nicotinamide adenine dinucleotide phosphate (NADP+)-linked  Has 2 step process: dehydrogenases: o Oxygen binding to active site o Biosynthetic pathways (i.e., fatty acid synthesis, o Bound oxygen is reduced or transferred to the steroid synthesis, pentose phosphate pathway) substrate Other dehydrogenases:  Flavin (Vitamin B2) derived: FMN/FAD-associated dehydrogenases o Associated with respiratory chain (Oxidized) (Reduced)  Other dehydrogenases – specific functions depending on the Dioxygenases metabolic pathway  Incorporate both oxygen atoms to the substrate o Examples are homogentisate dioxygenase, L- tryptophan dioxygenase Peroxidases Monooxygenases  Incorporate one oxygen atom to the substrate  H2O2 is reduced at the expense of the substrate (i.e., vitamin C, quinones, cytochrome c)  Prosthetic group: Protoheme o Example: Cytochrome P450 o Example: Glutathione peroxidase  Monooxygenases involved in steroid metabolism and detoxification of drugs  Site: Endoplasmic reticulum and mitochondria (ETC)  Organs: Liver and intestine BIOCHEMISTRY Prepared by: ARRIANE Date: SEPTEMBER 6, 2024 4 BIOCHEMISTRY Week 5: Bioenergetics and Biological Oxidation Prepared by: Arriane Lecturer: Farr Krizha I. Tangkusan, RN, MD Date: September 6, 2024 Notes:  Class II – involves transfer of electrons from FAD to FMN  Cytochrome b5 – found in the liver is important for drug metabolism, and responsible for detoxifying drugs and desaturation of fatty acids Superoxide dismutase (SOD)  Superoxide is formed when reduced flavins—present, for example, in xanthine oxidase—are reoxidized univalently by molecular oxygen  Transfer of single electron to O2 creates the potentially damaging superoxide anion free radicals which gives rise to free-radical chain reactions, amplifying its destructive effects  SOD protects aerobic organisms from oxygen toxicity BIOCHEMISTRY Prepared by: ARRIANE Date: SEPTEMBER 6, 2024 5