Metabolic Pathways

1. Metabolic Pathways How cells derive energy from organic fuel Pathways that yield energy by burning fuel Chapters 67-69

2. Metabolism • Is the sum total of all chemical reactions occurring throughout the body. It includes • Anabolic reactions-monomers to polymers (making larger molecules by attaching together many smaller ones, ex. Amino acids linked to form proteins.) Dehydration synthesis reactions (ex. Growth) • Catabolic reactions- polymers to monomers (cutting larger molecules into many smaller ones, ex. Hydrolyzing a protein into amino acids.) Hydrolysis reactions, ex. Digestive system

3. Metabolic Pathways • Cells quite literally “burn” fuel, much like your car engine burns gasoline, or fireplace burns logs. • It is a controlled burn – step by step, releasing “packets of energy” that can be stored in chemical bonds. • To burn anything completely and get the highest yield of energy, you require oxygen. O2 is not a fuel!

4. Metabolic Pathways • The more hydrogen atoms a molecule has (the more highly “reduced”), the more energy it contains. • Hydrogen atoms (and their electrons) are stripped off energy rich molecules and are passed on to O2. Oxygen is the final electron acceptor in the “oxidation” process. • Oxygen accepts the electrons, along with the hydrogen ions, that are stripped off any “energy rich” molecule.

5. Metabolism • The most commonly used, immediately available, fuel isglucose (dextrose) , but it can be other substrates as well, molecules like • Fats (very highly reduced, rich source of H) • amino acids • proteins (but this is reserved for emergencies only, as this actually burns down essential molecules in cells.) • Nucleic acids—in theory, could be a source of fuel, however the cell will NEVER use its DNA as a fuel—why?

6. Cells and Mitochondria • cells provide small organic molecules (fuel) to their mitochondria (the engines that will “burn the fuel”) • These molecules can come from carbohydrates, fatty acids or proteins • Mitochondria use these molecules to produce ATP • ATP is the cell’s “currency” used to perform cellular functions

7. Metabolism • cells carry out a “controlled burn”, otherwise you’d blow up like the picture shown! • cells burn their substrate-of-choice in a slow, organized way. They shuttle the energy from each step into a storage molecule. • cells use the extracted energy to form energy-rich chemical bonds. • Energy is shuttled to and stored in the form of chemical bonds, as in ADP + Pi ATP

8. Metabolism • Each ATP molecule is a quantum of energy formed by attaching a phosphate group onto ADP. • phosphate (Pi) is a bulky negatively charged group, • ADP is also highly negatively charged • it takes much energy to overcome their repulsion and tie them together. • Forcing them together and linking them requires energy. That’s where the chemical energy is stored (“potential energy.”) • this energy can be recovered later by breaking (hydrolyzing) the bond (reversible reaction.)- this is kinetic energy and can be used to do work—that is the cell can use the released energy to perform some other function (Na+/K+ ATPase) • This is the energy currency or “money” of the cell.

9. Gylycolysis • http://www.youtube.com/watch?v=x-stLxqPt6E

10. Glycolysis (“breaking down glucose”) • Anaerobic respiration (“in absence of oxygen”) of glucose • Enzymes to carry this out are located in cytoplasm of cells • In several steps, the atoms in a glucose molecule are rearranged to a lower energy state, the energy is then directly stored in the bonds of ATP • Yields ATP directly, without the utilization of oxygen, but only yields a small number of ATP per glucose (2) • AND it yields two molecules of NADH—this is a type of stored energy that can be “cashed in for ATP” in the mitochondrion. • The end-product of this process is pyruvate (2 molecules for each burned glucose) • Often, pyruvate is sometimes converted to lactate OR further hydrolyzed to acetate. Acetate can be linked to a carrier, CoA, forming acetyl-CoA-and this can be broken down for even more energy....to be continued!

11. Glycolysis—the breakdown of glucose to pyruvic acid • This process requires: • Glucose molecules • Cytoplasmic enzymes • ATP and ADP • Inorganic phosphate • NAD (nicotinamide adenine dinucleotide)- a coenzyme! It merely temporarily stores energy from hydrogen ion to cash it in for ATP in the mitochondria! YOU SHOULD KEEP TRACK OF THE AMOUNTS OF THESE CREATED (along with FADH2) • The overall reaction is: Lactate fermentation vs alcoholic fermentation? Are we talking humans or yeast? • Glucose + 2 NAD + 2 ADP + 2Pi  2 Pyruvic acid + 2 NADH + 2 ATP http://trc.ucdavis.edu/biosci10v/bis10v/media/ch06/fermentation.html

12. glycolysis http://trc.ucdavis.edu/biosci10v/bis10v/media/ch06/glycolysis.html

13. Krebs Cycle • http://www.youtube.com/watch?v=aCypoN3X7KQ

14. Citric Acid Cycle (Krebs’ cycle) or TCA cycle From glycolysis! • Aerobic respiration (utilizes oxygen) • Occurs inside mitochondria, where necessary enzymes are located. • Extracts hydrogen atoms, along with their electrons from 6-C citric acid (which is formed from 4-C oxaloacetate and 2-C acetyl CoA.) • 2ATP made here for every glucose • These are passed to coenzymes (temp storage of electrons), and then later passed down to the ETS to be completely oxidized (oxidative phosphorylation) • Total number of coenzyme carriers to cash in for every glucose (including preparatory phase): • NADH (8) • FADH2 (2) http://trc.ucdavis.edu/biosci10v/bis10v/media/ch06/prep_and_krebs.html

15. Oxidative phosphorylation and the ETShttp://images.google.com/imgres?imgurl=http://vcell.ndsu.nodak.edu/animations/etc/images/etc-mov.jpg&imgrefurl=http://vcell.ndsu.nodak.edu/animations/etc/index.htm&h=125&w=130&sz=9&hl=en&start=2&tbnid=HBWChNaHruPl9M:&tbnh=88&tbnw=91&prev See video at this web-site!! Very helpful! • A chain of enzymes (cytochromes) located inside mitochondrial (matrix) attached to the inner membrane (cristae) • Involved in passing down hydrogen atoms and their accompanying electrons as they extract the energy in them and pass the energy on by storing it in ATP bonds. (ADP + Pi ATP) • The last receiver in the chain is oxygen. • Oxygen will receive 2 hydrogen atoms, to become a water molecule (byproduct) • This is where we cash in the NADH and FADH2 • Get 2.5 ATP for every NADH and 1.5 ATP for every FADH2 http://www.stanford.edu/group/hopes/treatmts/ebuffer/f_j13electtrans.jpg

16. Energy yield per molecule of glucose 3 3 20 20 3 3 30

17. COH- 1:2:1 • Monosaccharides • Simple sugar • Up to seven carbons • Isomers- D-, L- glucose, fructose • Disaccharides • Two mono’s bound together • Sucrose • Polysaccharides • Cellulose • Starch • glycogen Why would it be important to store sugar in a polymer form? Hint: think osmotic gradient!

19. Lipids • Very little oxygen (carbon and hydrogen atoms abound—Yeah! More fuel!) • Give off more energy than COH • Fatty acids • Eicosanoids- come from arachadonic acid; prostaglandins example • Glycerides • Steroids- sex hormones, cholesterol, bile salts • Phospholipids • glycolipids

20. Glycerides • Can be attached to fatty acids • Monoglyceride • Diglyceride • Triglyceride • Energy source • Insulation • protection

21. Phospholipids and Glycolipids • Phospholipids have phosphate group attached to diglyceride • Glycolipids have a COH attached to diglyceride • Polar Heads • Non-polar tails (hydrophobic) • Head to tail configuration or micelle

22. Lipids- Fatty Acids • COOH- head • Carbon tail • Saturated • Unsaturated • The process by which fatty acids are burned to retrieve the energy stored in its bonds. • Fatty acids are long chains of carbon atoms (often 20 or more C’s) with many hydrogen atoms attached. • Fatty acids are highly reduced (energy rich) molecules. • Beta oxidation is a repeating 4 step process in which sequential 2-C groups (“acetyl groups”) are cut from the long chain; they are attached to a carrier (CoA) and then shuttled into the mitochondria • These 2-C groups are then burned in the Krebs’ cycle.

23. Lipid catabolism • Lipolysis • Lipids broken down into pieces that can be converted into pyruvate • Triglycerides are split into glycerol and fatty acids • Glycerol enters glycolytic pathways • Fatty acids enter the mitochondrion via carnitine translocase (rate limiting factor) • Beta-oxidation • Breakdown of fatty acid molecules into 2-carbon fragments • Enter the TCA • Lipids and energy production • Cannot provide large amounts in ATP in a short amount of time • Used when glucose reserves are limited

24. Fats burn in the flame of carbohydrates– if no oxaloacetate, then NO krebs cycle and acetyl-CoA will become ketone bodies and lead to ketoacidosis— • Ketone bodies leads to sweet breath Acetoacetate - hydroxybutyrate acetone

25. Amino acid catabolism • If other sources inadequate, mitochondria can break down amino acids • TCA cycle • removal of the amino group • Deamination –generating NH4+ and NADH • Proteins are an impractical source of ATP production

26. Nucleic Acids • DNA • RNA • DNA is never catabolized for energy • RNA catabolism • RNA molecules are routinely broken down and replaced • Generally recycled as nucleic acids • Can be catabolized to simple sugars and nitrogenous bases • Do not contribute significantly to energy reserves • Nitrogenous ring • Pyrimidines (C,T, U) • Purines (A, G) • Pentose sugar • Phosphate group--mono, di or tri