Bioenergetics and metabolic pathways

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1 Bioenergetics and metabolic pathways BIOB111 CHEMISTRY & BIOCHEMISTRY Session 19

2 Session Plan Introduction to Bioenergetics Metabolism Metabolic Pathways Metabolism & Cell Structure Mitochondria Compounds in Metabolic Pathways High-energy Phosphates Coenzymes NAD & FAD Coenzyme A Overview of Bioenergetic Pathways

3 Bioenergetics The study of energy transformation / energy flow through living systems. Energy that is involved in making & breaking of chemical bonds in the molecules found in biological organisms. It can also be defined as the study of energy relationships & energy transformations in living organisms. The energy, required to run the human body, is obtained from ingested foods that are broken down in several different catabolic pathways.

4 Metabolism Is the total sum of all biochemical reactions that take place in a living cell. 1) CATABOLISM Metabolic reactions in which large bio-molecules are broken down into smaller ones. Energy is released Oxidation of glucose 2) ANABOLISM Metabolic reactions in which small bio-molecules are joined together to form larger ones. Energy is required Synthesis of proteins from amino acids

5 Stoker 2104, Figure 23-1 p842

6 Metabolic Pathway Is a series of consecutive biochemical reactions, used to convert a starting material into an end product. The major metabolic pathways are similar for all life forms scientists study metabolic reactions in simple life forms to understand the same reactions in humans. Linear pathways series of reactions generates a final product. Cyclic pathways series of reactions generates the first reactant.

7 Metabolism & Cell Structure Cell structure knowledge is essential to understanding of metabolism. Prokaryotic Cell Single compartment organism No nucleus -- found only in bacteria Single circular DNA molecule present near center of the cell (nucleoid). Eukaryotic Cell Multi-compartment cell DNA is present in the membrane enclosed nucleus Cell is compartmentalized into cellular organelles ~1,000 times larger than bacterial cells.

8 Eukaryotic Cell Diagram Stoker 2014, Figure 23-2 p843

9 Mitochondria Are the power-stations of the cell that generate cellular energy (ATP). Have a double membrane Inner & Outer membrane that are separated by the Intermembrane space. Matrix the most interior region within the Inner membrane. Outer Mitochondrial Membrane 50% lipid & 50% protein is permeable to most molecules & ions Inner Mitochondrial Membrane 20% lipids & 80% protein highly impermeable to most substances Is highly folded to increase surface area, forming Cristae enzymes, ATP synthase complexes, are attached to cristae.

10 Stoker 2014, Figure 23-3 p844

11 Compounds in Metabolic Pathways Several Nucleotide-Containing Compounds play an important role in metabolic pathways. Adenosine Phosphates Other Nucleotide Triphosphates Flavin Adenine Dinucleotide (FAD) Nicotinamide Adenine Dinucleotide (NAD) Coenzyme A (CoA)

12 Adenosine Phosphates Several Adenosine Phosphates exist: AMP Adenosine Monophosphate an RNA nucleotide ADP Adenosine Diphosphate key molecule in metabolic pathways ATP Adenosine Triphosphate key molecule in metabolic pathways There are 2 different types of bonds between phosphates: Phospho-ester bond = the phosphate-ribose bond. Phospho-anhydride bond = phosphate-phosphate bond a very reactive bond, requires less energy to break.

13 Adenosine Phosphates Stoker 2014, Figure 23-4 p846

14 ATP Hydrolysis ATP & ADP molecules readily undergo hydrolysis reaction, in which phosphate groups (P i ) are released.

15 ATP Hydrolysis Stoker 2014, Figure 23-5 p kcal/mol 7.3 kcal/mol

16 ATP Function In cellular reactions ATP functions as both, a source of a phosphate group & a source of energy. e.g. Conversion of glucose to glucose-6-phosphate

17 Other Nucleotide Triphosphates Other bases can also form nucleotide triphosphates: UTP Uridine Triphosphate Involved in carbohydrate metabolism GTP Guanosine Triphosphate Involved in carbohydrate & protein metabolism CTP Cytidine Triphosphate Involved in lipid metabolism

18 Flavin Adenine Dinucleotide (FAD) A coenzyme required in many metabolic redox reaction. Contains B vitamin Riboflavin (vitamin B2) Flavin heterocyclic amine Ribitol alcohol derived from ribose

19 FAD Structure Stoker 2014, Figure 23-6a p849

20 FAD Function To be able to participate in redox reactions, FAD exists in 2 forms: FAD oxidized form FADH 2 reduced form In metabolic pathways FAD continuously changes between its oxidized & reduced forms & acts as an electron carrier.

21 FAD Function Stoker 2014, p850

22 Nicotinamide Adenine Dinucleotide Another coenzyme required in many metabolic redox reaction. Contains B vitamin Niacin in the form of Nicotinamide (vitamin B3)

23 NAD Structure Stoker 2014, Figure 23-6b p849

24 NAD Function To be able to participate in redox reactions, NAD exists in 2 forms: NAD + oxidized form NADH reduced form In metabolic pathways NAD continuously changes between its oxidized & reduced forms & acts as an electron carrier.

25 NAD Function

26 Coenzyme A (CoA) Stoker 2014, Figure 23-7 p851 Contains: 2-aminoethanethiol the functional group of CoA is SH (Thiol) B vitamin Panthotenic acid (vitamin B5) Phosphorylated ADP with a P i on 3 of the ribose

27 CoA Structure Stoker 2014, Figure 23-7 p852

28 CoA Function A refers to the metabolic function of CoA = transfer of ACETYL groups (= C 2 fragments) in metabolic pathways, in the form of Acetyl CoA.

29 Overview of Bioenergetic Pathways The energy, required to run the human body, is obtained from ingested foods that are broken down in several different catabolic pathways. There are 4 general stages in the biochemical energy production. Stage 1 Digestion Stage 2 Acetyl group formation Stage 3 Citric acid cycle Stage 4 Electron transport chain & Oxidative phosphorylation

30 Digestion The digestion of carbohydrates, lipids & proteins begins in the mouth, continues in the stomach & is completed in the small intestine. Many digestive enzymes are used in this process. Results in production of small molecules that can cross intestinal membrane into the blood End-products of digestion Glucose & other monosaccharides from carbohydrates Amino acids from proteins Fatty acids & glycerol from fats & oils The digestion products are absorbed across the intestinal wall into the bloodstream & transported to all body cells.

31 Acetyl Group Formation This stage involves many reactions, some of which occur in the cytosol & others in the mitochondria. The small molecules from Digestion are further oxidized during this stage. End-product of these oxidations are C 2 fragments = Acetyl groups. Acetyl groups attach to CoA & form Acetyl CoA.

32 Citric Acid Cycle Takes place in the mitochondria Acetyl groups are oxidized & produce CO 2 & energy Most energy is trapped in reduced coenzymes NADH & FADH 2 & carried to the 4 th stage. Some energy produced in this stage is lost in the form of heat The CO 2 we exhale comes primarily from this stage

33 ETC & OP Takes place in mitochondria NADH & FADH 2 provide H + & electrons needed for ATP production H + are transported to the inter-membrane space in mitochondria Electrons are transferred to molecular O 2, which is reduced to H 2 O. H + reenter the mitochondrial matrix & drive ATP-synthase reaction to produce ATP

34 Common Metabolic Pathway The reactions in stages 3 & 4 are the same for all types of foods (carbohydrates, fats & proteins). These reactions constitute the Common Metabolic Pathway (CMP), producing energy in the form of ATP. The CMP is the total sum of the biochemical reactions of the Citric Acid Cycle, Electron Transport Chain & Oxidative Phosphorylation. The CMP takes place in the mitochondria.

35 Stoker 2014, p859

36 Readings & Resources Stoker, HS 2014, General, Organic and Biological Chemistry, 7 th edn, Brooks/Cole, Cengage Learning, Belmont, CA. Stoker, HS 2004, General, Organic and Biological Chemistry, 3 rd edn, Houghton Mifflin, Boston, MA. Timberlake, KC 2014, General, organic, and biological chemistry: structures of life, 4 th edn, Pearson, Boston, MA. Alberts, B, Johnson, A, Lewis, J, Raff, M, Roberts, K & Walter P 2008, Molecular biology of the cell, 5 th edn, Garland Science, New York. Berg, JM, Tymoczko, JL & Stryer, L 2012, Biochemistry, 7 th edn, W.H. Freeman, New York. Dominiczak, MH 2007, Flesh and bones of metabolism, Elsevier Mosby, Edinburgh. Tortora, GJ & Derrickson, B 2014, Principles of Anatomy and Physiology, 14 th edn, John Wiley & Sons, Hoboken, NJ. Tortora, GJ & Grabowski, SR 2003, Principles of Anatomy and Physiology, 10 th edn, John Wiley & Sons, New York, NY.

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