Glycolysis, Dr Muhammad Arshad PhD (UAF)

1. Glycolysis, Dr Muhammad Arshad PhD (UAF)

2. Metabolism • In cells, the reactions rarely occur in isolation but, rather, are organized into multistep sequences called pathways, such as that of glycolysis • In a pathway, the product of one reaction serves as the substrate of the subsequent reaction. • Different pathways can also intersect, forming an integrated and purposeful network of chemical reactions. • These are collectively called metabolism, (the sum of all the chemical changes occurring in a cell, a tissue, or the body) • Most pathways can be classified as either catabolic (degradative) or anabolic (synthetic). • The Pathways that regenerate a component are called cycles.

3. Metabolic Map • It is convenient to investigate metabolism by examining its component pathways. • Each pathway is composed of multienzyme sequences, and each enzyme, in turn, may exhibit important catalytic or regulatory features. • To provide the “big picture,” of metabolism a metabolic map containing the important central pathways of energy metabolism is presented. • The map is useful in tracing connections between pathways, visualizing the purposeful “movement” of metabolic intermediates, • and depicting the effect on the flow of intermediates if a pathway is blocked.

5. Catabolic pathways • Catabolic reactions serve to capture chemical energy in the form of adenosine triphosphate (ATP) from the degradation of energy-rich fuel molecules. • Catabolism also allows molecules in the diet (or nutrient molecules stored in cells) to be converted into building blocks needed for the synthesis of complex molecules. Energy generation • by degradation of complex molecules occurs in three stages as shown in Figure 8.3. • [Note: Catabolic pathways are typically oxidative, and require oxidized coenzymes • such as nicotinamide adenine dinucleotide (NAD+).]

6. Anabolic pathways • Anabolic reactions combine small molecules, such as amino acids, to form complex molecules such as proteins. • Anabolic reactions require energy, which is generally provided by the hydrolysis of ATP and inorganic phosphate (Pi). • Anabolic reactions often involve chemical reductions in which the reducing power is most frequently provided by the electron donor NADPH.

7. Major pathways of glucose utilization

8. Regulation Of Metabolism • The pathways of metabolism must be coordinated so that the production of energy or the synthesis of end products meets the needs of the cell. • Furthermore, individual cells do not function in isolation but, rather, are part of a community of interacting tissues. Thus, a sophisticated communication system has evolved to coordinate the functions of the body. • Regulatory signals that inform an individual cell of the metabolic state of the body as a whole include hormones, neurotransmitters, and the availability of nutrients. These, in • turn, influence signals generated within the cell

9. Intracellular communication • The rate of a metabolic pathway can respond to regulatory signals that arise from within the cell. • For example, the rate of a pathway may be influenced • By the availability of substrates, • Product inhibition, • Alterations in the levels of allosteric activators or inhibitors. • These intracellular signals typically elicit rapid responses, and • are important for the moment-to-moment regulation of metabolism

10. Intercellular communication • Signaling between cells provides for long-range integration of • metabolism and usually results in a response, such as a change in gene expression, that is slower than is seen with intracellular signals. • Communication between cells can be mediated, for example, • surface-to-surface contact • Formation of gap junctions, • Allowing direct communication between the cytoplasms of • adjacent cells. • the most important route of communication is chemical signaling between cells by blood borne hormones or by • neurotransmitters.

11. Second messenger systems • “Second messenger” molecules, so named because • they intervene between the original messenger and • the ultimate effect on the cell, are part of the cascade of events that translates hormone or neurotransmitter binding into a cellular response. • Calcium/phosphatidylinositol system • The adenylyl cyclase system, which is particularly important in regulating the pathways of intermediary metabolism. • Adenylyl cyclaseThis is a membrane-bound enzyme that converts ATP to 3ʹ,5ʹ-adenosine monophosphate. • G Proteins: • Protein kinases: • Dephosphorylation of proteins • Hydrolysis of cyclic adenosine monophosphate

12. The first phase of glycolysis (the preparatory phase)

13. The second phase of glycolysis (the payoff phase) O

14. The two phases of glycolysis

15. Three possible catabolic fates of the pyruvate formed in glycolysis

16. 1. Phosphorylation of glucose

17. 2. Conversion of glucose 6-phosphate to fructose 6-phosphate

18. 3. Phosphorylation of fructose 6-phosphate to fructose 1,6-bisphosphate

19. 4. Cleavage of fructose 1,6-bisphosphate

20. 6. Oxidation of glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate

21. 8. Conversion of 3-phosphoglycerate to 2-phosphoglycerate

22. 9. Dehydration of 2-phosphoglycerate to phosphoenolpyruvate

23. 10. Transfer of the phosphoryl group from phosphoenolpyruvate to ADP

24. Entry of glycogen, starch, disaccharides, and hexoses into the preparatory stage of glycolysis Feeder pathways for glycolysis

25. Feeder pathways for glycolysis

26. Dietary polysaccharides and disaccharides undergo hydrolysis to monosaccharides

27. Glycogen breakdown by glycogen phosphorylase

28. Other monosaccharides enter the glycolytic pathway at several points

29. Conversion of galactose to glucose 1-phosphate Defects in any of the three enzymes in this phatway Cause galactosemia in humans Galactose methabolite involved in galactokinase-deficiency galactosemia

30. Fates of pyruvate under anaerobic conditions: Fermentation Pyruvate is the terminal electron acceptor in lactic acid fermentation no net change in NAD+ or NADH acidification in muscle and blood limits the period of vigorous activity

31. Ethanol is the reduced product in ethanol fermentation tightly bound coenzyme, thiamine pyrophosphate Industrial-scale fermentations yield a variety of common foods and industrial chemicals

32. Thiamine pyrophosphate

33. Gluconeogenesis Carbohydrate synthesis from simple precursors

34. Opposing pathways of glycolysis and gluconeogenesis in rat liver