Intermediary Metabolism

1. Intermediary Metabolism M.F.Ullah, Ph.D • COURSE TITLE: BIOCHEMISTRY 2 COURSE CODE: BCHT 202 PLACEMENT/YEAR/LEVEL: 2nd Year/Level 4, 2nd Semester

2. Definition…. Metabolismcomprises the entire set of chemical reactions that occur in a living organism that allow it to grow, reproduce, maintain its structure and respond to the environment. These chemical reactions form an intricate network of pathways and cycles which are regulated depending upon the needs of the cells. Significance/ Purpose Metabolismis a highly coordinated cellular activity in which many multi-enzyme systems (metabolic pathways) cooperate to: (1) obtain chemical energy by degrading energy-rich nutrients from the environment; (2) convert nutrient molecules into the cell’s own characteristic molecules, including precursors of macromolecules; (3) polymerize monomeric precursors into macromolecules: proteins, nucleic acids, and polysaccharides; and (4) synthesize and degrade biomolecules required for specialized cellular functions, such as membrane lipids, intracellular messengers

3. Intermediarymetabolism The term intermediary metabolism is often applied to the combined activities of all the metabolic pathways occurring in a living organism that in a step wise manner convert : a). Precursors into metabolites, products and energy and b). inter-converts metabolites, products and energy into precursors, thereby maintaining the structural and functional integrity of a cell. Example:A diet containing carbohydrate, protein and fat undergoes following metabolic pathways collectively called intermediary metabolism Intermediates Starch Glucose Glucose Glycogen Intermediates Amino acids Dietary proteins Amino acids Cellular Proteins Intermediates Dietary fats Fatty acids Membrane lipids Fatty acids

5. Metabolic Pathway The sum of all the chemical transformations taking place in a cell, occurs through a series of enzyme-catalyzed reactions that constitute metabolic pathways. Each of the consecutive steps in a metabolic pathway from starting compound (precursor) to the final end product produce metabolic intermediate called metabolites. Example: Glycolysis is a metabolic pathway and Fructose-1,6-bisP is one of it metabolite Metabolic pathways can be linear Such as glycolysis or cyclic such as TCA In general metabolism is classified into two types of processes: Catabolic processes Anabolic processes

6. Catabolismis the degradative phase of metabolism in which organic nutrient molecules (carbohydrates, fats, and proteins) are converted into smaller, simpler end products (such as lactic acid, CO2, NH3). Catabolic pathways release energy, some of which is conserved in the formation of ATP and reduced electron carriers (NADH, NADPH, and FADH2); the rest is lost as heat. Example: Carbohydrate catabolism Energy Glycogen Glucose Pyruvate Acetyl CoA Co2+ H2O

7. Anabolismis the biosynthetic phase of metabolism in which small, simple precursors are built up into larger and more complex molecules, including lipids, polysaccharides, proteins, and nucleic acids. Anabolic reactions require an input of energy, generally in the form of the phosphoryl group transfer potential of ATP and the reducing power of NADH, NADPH, and FADH2 Example: Carbohydrate Anabolism Energy Pyruvate Oxaloacetate Glucose Glycogen

8. Relationships between catabolic and anabolic Pathways: Catabolic pathways deliver chemical energy in the form of ATP, NADH, NADPH, and FADH2. These energy carriers are used in anabolic pathways to convert small precursor molecules into cell macromolecules.

9. In general, catabolic pathways are convergent and anabolic pathways are divergent

10. Carbohydrate catabolism Glycogenolysis: glycogen → glucose 1-phosphate → blood glucose Glycolysis: glucose → pyruvate Carbohydrate anabolism Gluconeogenesis: citric acid cycle intermediates → glucose Glycogen synthesis: glucose 6-phosphate → glucose 1-phosphate → glycogen

11. Integration of Metabolism: The metabolic pathways for carbohydrate, protein and fat are integrated and the point of integration is served by certain common metabolites (intermediates). It is through these points of integration feeder pathways often act to replenish the exhausting metabolites of one pathway by utilizing the common metabolic intermediate produced by the other pathway.

12. Metabolic Integration Carbohydrate metabolism Fat metabolism Proteinmetabolism Fat metabolism Proteinmetabolism Proteinmetabolism Proteinmetabolism Proteinmetabolism Proteinmetabolism

14. Lipid Metabolic Reactions

15. Biomolecules & Energy relationship DIETARY FUELS The major fuels we obtain from our diet are carbohydrates, proteins, and fats. When these fuels are oxidized to CO2 and H2O in our cells, energy is released by the transfer of electrons to O2. The energy from this oxidation process generates heat and adenosine triphosphate (ATP) . Carbon dioxide travels in the blood to the lungs, where it is expired, and water is excreted in urine, sweat, and other secretions. Although the heat that is generated by fuel oxidation is used to maintain body temperature, the main purpose of fuel oxidation is to generate ATP. ATP provides the energy that drives most of the energy-consuming processes in the cell, including biosynthetic reactions, muscle contraction, and active transport across membranes. As these processes use energy, ATP is converted back to adenosine diphosphate(ADP) and inorganic phosphate (Pi).

16. The oxidation of fuels to generate ATP is called respiration . Before oxidation, carbohydrates are converted principally to glucose, fat to fatty acids, and protein to amino acids. The pathways for oxidizing glucose, fatty acids, and amino acids have many features in common. They first oxidize the fuels to acetyl CoA, a precursor of the tricarboxylic acid (TCA) cycle. The TCA cycle is a series of reactions that completes the oxidation of fuels to CO2 . Electrons lost from the fuels during oxidative reactions are transferred to O2 by a series of proteins in the electron transport chain. The energy of electron transfer is used to convert ADP and Pi to ATP by a process known as oxidative phosphorylation. In discussions of metabolism and nutrition, energy is often expressed in units of kilocalorie (kcal). Energy is also expressed in kilojoules. One kilocalorie equals 4.18 kilojoules (kJ).

17. Carbohydrates The major carbohydrates in the human diet are starch, sucrose, lactose, fructose, and glucose. The polysaccharide starch is the storage form of carbohydrates in plants. Sucrose (table sugar) and lactose (milk sugar) are disaccharides, and fructose and glucose are monosaccharides. Digestion converts the larger carbohydrates to monosaccharides, which can be absorbed into the bloodstream. Glucose, a monosaccharide, is the predominant sugar in human blood. Oxidation of carbohydrates to CO2 and H2O in the body produces approximately 4 kcal/g . In other words, every gram of carbohydrate we eat yields approximately 4 kcal of energy. Note that carbohydrate molecules contain a significant amount of oxygen and are already partially oxidized before they enter our bodies.

18. Proteins Proteins are composed of amino acids that are joined to form linear chains. In addition to carbon, hydrogen, and oxygen, proteins contain approximately 16% nitrogen by weight. The digestive process breaks down proteins to their constituent amino acids, which enter the blood. The complete oxidation of proteins to CO2, H2O, and NH4 in the body yields approximately 4 kcal/g.

19. Our major fuel store is adipose triacylglycerol (triglyceride), a lipid more commonly known as fat. Fats Fats are lipids composed of triacylglycerols (also called triglycerides). A triacylglycerol molecule contains 3 fatty acids esterified to one glycerol moiety. Fats contain much less oxygen than is contained in carbohydrates or proteins. Therefore, fats are more reduced and yield more energy when oxidized. The complete oxidation of triacylglycerols to CO2 and H2O in the body releases approximately 9 kcal/g, more than twice the energy yield from an equivalent amount of carbohydrate or protein.

22. A case study Mr. Steve recently discovered that he has put on much weight during the last 2 months. He was concerned about his health and so he went to Dr. Smith, a dietician for an advice. Dr. Smith advised him to restrict his fat, carbohydrate and protein intake to 50% of the current intake. An analysis of Mr. Steve’s current diet showed that he ate 300 g carbohydrate, 60 g protein and 80 g fat each day. Calculate the caloric restriction imposed on Mr. Smith by his dietician.

23. Caloric restriction is the number of calories permitted to be consumed STEP 1:Considering the current diet to be 100% , reduction by 50% will give dietary restriction of: 100% - 50% = 50% STEP 2: Now calculate 50% of each of the content of the current diet to get the recommended diet Carbohydrate : Current content = 300g Recommended - 50/100 x 300 = 150g Protein : Current content 60 g Recommended – 50/100x60= 30 g Fat: Current content= 80 g Recommended- 50/100x80= 40g STEP 3: Now calculate the calories from each of the recommended content and add up: Carbohydrate: 300x4= 1200 Kcal (4Kcal/g) Protein : 30x 4= 120 Kcal (4 Kcal/g) Fat: 40x9= 360 Kcal (9 Kcal/g) Total calories= …….. Kcal (permitted to be consumed or caloric restriction) In Kjoules : ……..x 4.18=2570 KJ (1 Kcal=4.18 KJ)

24. Suggested readings Available in the University Library Marks’ Basic Medical Biochemistry: A Clinical Approach Lippincott Wiliams & Wilkins