Review of Basic Metabolic Principles

1. Review of Basic Metabolic Principles A. Energy Currency of the Cell • Metabolic pathways can be classified as either: • energy generating (catabolic)…or • energy utilizing (anabolic) The cell also uses two types of energy currency: • 1. Phosphate anhydrides(compounds with high • phosphate transfer potential) General: hydrolysis of a phosphate ester + + ATP hydrolysis ATP + +

2. Free Energies of hydrolysis of some phosphorylated • compounds • ATP is the most commonly used compound with • high phosphate transfer potential • phosphoenolpyruvate & creatine phosphate • have enough energy to synthesize ATP • ATP can be used to synthesize glucose 6- • phosphate & similar compounds • GTP is sometimes used in place of ATP

3. ATP is called the energy currency of the cell Catabolism Anabolism O2 Work Heat ATP Foods Biosynthesis CO2 + H2O [Energy] • Definitions: • catabolism is the production of energy from • food • anabolism is the utilization of energy to provide • heat, do work, or drive biosynthetic reactions • Reducing equivalents(compounds with high • electron transfer potential) Foods → NADH and FADH2 → ATP for Biosynthesis • The reducing equivalents in the foods we eat… • are transferred to NADH and FADH2 • NADH and FADH2 transfer their electrons to • the electron transport chain which.. • uses the energy in those electrons to synthesize • ATP

4. Based on what you already know, you might predict • that: • catabolic pathways produce NADH, FADH2, & • ATP • anabolic pathways utilize ATP, NADH, & FADH2 • However, that’s not quite true. In reality: • catabolic pathways produce NADH, FADH2, & • ATP • anabolic pathways utilize ATP, NADPH, & FADH2 B. Coenzymes 1. Definition • Coenzymes are small molecular weight • compounds that are: • necessary for the catalytic activity of • one or more enzymes • present in very small amounts compared • to the substrates of the enzyme • used over & over in a catalytic manner • most coenzymes exist free in solution • some coenzymes are bound to proteins • = prosthetic groups

5. 2. Coenzymes carry some biologically important • chemical group in an “activated” (high energy) • form so that it can be used in biosynthetic • reactions Example = coenzyme A (carries acyl groups) + CoASH + H20 acetic acid acetyl CoA G = -7.5 kcal/mole + CoASH + H20 acyl CoA carboxylic acid

6. 3. Coenzymes are sometimes derived from vitamins Some activated carriers in metabolism

7. C. What Does a Metabolic Pathway Look Like? • many reversible reactions • a few irreversible reactions that drive the • pathway • the irreversible reactions are important! A B C D E F E1 E2 E3 E4 E5 D. Control of Metabolism 1. Controls Which Operate at a Cellular Level • regulation is by inhibitors & activators in cell a. Which metabolites usually regulate pathways? • The precursor of a pathway usually • stimulates the pathway + A B C D E • ii. The end product of a pathway usually • inhibits the pathway - A B C D E

8. iii. The end product of a competing pathway • often stimulates the other pathway A B C D E + G H I • Energy utilizing & producing pathways • are often regulated on the basis of • ATP supply in the cell • Catabolic pathways are inhibited by • ATP and/or stimulated by ADP or AMP • Anabolic pathways are stimulated by • ATP and/or inhibited by ADP or AMP b. Where are pathways regulated? i. At or near a branch point D A * B * C

9. ii. At 1st committed (irreversible) step * A B C D E 2. Controls that operate at whole body level • sites of regulation similar, but mechanisms different • Peptide hormones (glucagon, epinephrine, • & insulin) • act via second messenger (eg, cAMP) • result in phosphorylation or dephosphoryl- • ation • alter enzyme activity • are fast acting b. Steroid hormones (cortisol) • travel to nucleus & bind to DNA • affect amount of enzyme made • are slower acting

10. Pi O + OPi E. Glossary of Enzyme Names • Kinase: catalyzes the phosphorylation of some • metabolite, usually with ATP as the donor Example = glucokinase or hexokinase ATP + glucose → ADP + glucose 6-phosphate • Phosphatase: catalyzes the hydrolytic removal • of a phosphate group (also called • dephosphorylation) Example = glucose 6-phosphatase glucose 6-phosphate + H2O → glucose + Pi • Phosphorylase: catalyzes the phosphorolytic • cleavage of a bond (phosphate is the • attacking nucleophile) Example = glycogen phosphorylase

11. Hydrolase: catalyzes the hydrolytic cleavage of • some bond (water is the attacking nucleophile) • Often subclassified according to bond cleaved • Esterase: hydrolyzes ester bond • Peptidase: hydrolyzes peptide bond • Phospholipase: hydrolyses phospholipids • Dehydrogenase: catalyses oxidation-reduction • reactions by the transfer of hydrogens • (electrons). Generally use NAD+/NADH or • FAD/FADH2. Example = lactate dehydrogenase • Synthetase or synthase: catalyzes the joining of • two molecules to create a larger molecule Example: citrate synthase oxaloacetate + acetylCoA + H2O → citrate + CoASH (4 carbons) (2 carbons) (6 carbons)

12. Carboxylase: catalyzes the addition of CO2 to a • molecule. Uses biotin as a coenzyme Example = pyruvate carboxylase OAA + ADP + Pi pyruvate + CO2 + ATP + H2O • Transferase: catalyzes the transfer of a group from • one molecule to another. Subclassified • according to group transferred • Transaminase: transfers amino groups. Uses • pyridoxal phosphate as a coenzyme. Example = aspartate transaminase (AST) + + -ketoglutarate Aspartate Glutamate Oxaloacetate

13. Transaldolase: transfers aldehyde groups. Uses • thiaminepyrophosphate as a coenzyme aldehyde: • Transketolase: transfers ketone groups. Uses • thiaminepyrophosphate as a coenzyme ketone: • Acyltransferase: transfers acyl (carboxylic acid) • groups. Uses coenzyme A as a coenzyme acyl (carboxylic acid): Methyltransferase: transfers methyl groups. Decarboxylase: removes carboxyl groups as CO2 Isomerase: converts from one isomer to another