1. Chapter 24 Biosynthetic Pathways Chemistry 203

2. Catabolic reactions: Anabolic reactions:Biosynthetic reactions Complex molecules  Simple molecules + Energy Simple molecules + Energy (in cell)  Complex molecules Metabolism

3. Biosynthetic pathways Anabolic and catabolic reactions have different pathways. 1. Flexibility: if a normal biosynthetic pathway is blocked, the organism can often use the reverse of the catabolic pathway for synthesis. Complex Molecule Simple Molecules Catabolic Biosynthetic

4. 2. Overcoming Le Chatelier’s principle: Biosynthetic pathways If a dynamic equilibrium is disturbed by changing the conditions, the position of equilibrium moves to counteract the change.

5. Biosynthetic pathways Anabolic and catabolic reactions need different energy. Anabolic and catabolic reactions take place in different locations. Catabolic reactions Anabolic reactions Mitochondria Cytoplasm

6. Biosynthetic pathways 1. Biosynthesis of Carbohydrates 2. Biosynthesis of Lipids Biosynthesis of Fatty acids Biosynthesis of Membrane Lipids 3. Biosynthesis of Amino acids

7. Glycolysis Glucose is converted to two molecules of pyruvate. An anaerobic reaction in cytoplasm. 10 Reactions

8. Glycolysis Steps [1] – [5] energy investment phase: The 6-carbon glucose molecule is converted into two 3-carbon segments. 2 ATP molecules are hydrolyzed.

9. Glycolysis Steps [6] – [10] energy-generating phase: producing 1 NADH and 2 ATPs for each pyruvate formed.

10. Glycolysis Enzymes:

11. Step [1] begins with the phosphorylation of glucose into glucose 6-phosphate, using an ATP and a kinase enzyme. Glycolysis

12. Step [2] isomerizes glucose 6-phosphate to fructose 6-phosphate with an isomerase enzyme. Glycolysis

13. Step [3] is the phosphorylation of fructose 6-phosphate into fructose 1,6-bisphosphate with a kinase enzyme. Glycolysis

14. Overall, the first three steps of glycolysis: 1.2 phosphate groups is added. 2.A 6-membered glucose ring is isomerized into a 5-membered fructose ring. 3. The energy stored in 2 ATP molecules is utilized to modify the structure of glucose

15. Glycolysis Step [4] cleaves the fructose ring into a dihydroxy-acetone phosphate and a glyceraldehyde 3-phosphate.

16. Step [5] isomerizes the dihydroxyacetone phosphate into another glyceraldehyde 3-phosphate. Glycolysis Thus, the first phase of glycolysis converts glucose into 2 glyceraldehyde 3-phosphate units and 2 ATP is used.

17. In step [6] the aldehyde end of the molecule is oxidized and phosphorylated by a dehydrogenase enzyme and NAD + ; this produces 1,3-bisphospho-glycerate and NADH. Glycolysis

18. In step [7], the phosphate group is transferred onto an ADP with a kinase enzyme, forming 3-phosphoglycerate and ATP.

19. In step [8], the phosphate group is isomerized to a new position in 2-phosphoglycerate. Glycolysis

20. In step [9], water is lost to form phosphoenol-pyruvate. Glycolysis

21. In step [10], the phosphate is transferred to an ADP, yielding pyruvate and ATP with a kinase enzyme.

22. The 2 glyceraldehyde 3-phosphate units are converted into 2 pyruvate units in phase two of glycolysis. Overall, the energy-generating phase forms 2 NADHs and 4 ATPs. Glycolysis

23. Overall of glycolysis 2 ATPs are used in phase one of glycolysis, and 4 ATPs are made in phase two of glycolysis. The net result is the synthesis of 2 ATPs from glycolysis. The 2 NADHs formed are made in the cytoplasm and must be transported to the mitochondria to join the electron transport chain and make ATP.

24. under aerobic conditions under anaerobic conditions in fermentation by microorganisms The fate of pyruvate

25. Aerobic conditions The NADH formed needs O 2 to return to NAD +, so without O 2 no additional pyruvate can be oxidized. Pyruvate must diffuse across the outer and inner membrane of mitochondria into the matrix.

26. Fermentation is the anaerobic conversion of glucose to ethanol and CO 2 by yeast and other microorganisms. Fermentation

27. 1. Biosynthesis of Carbohydrates (from sun) In plants 6CO 2 Photosynthesis

28. 1. Biosynthesis of Carbohydrates In animals When both glucose and stored glycogen are depleted, glucose can be synthesis by gluconeogenesis. Intermediates of Glycolysis and Citric acid cycle are used to produce glucose. Gluconeogenesis is not the exact reversal of glycolysis: pyruvate to glucose does not occur by reversing the steps of glucose to pyruvate. (in liver)

29. 1. Biosynthesis of Carbohydrates Only four enzymes are unique. (compare to glycolysis) ATP is produced in glycolysis and used up in gluconeogenesis.

30. Lactate from glycolysis in muscle is transported to the liver, where gluconeogenesis converts it back to glucose. Cori Cycle

31. Gluconeogenesis Glucose is the main source of energy for cells and the only source of energy used by the brain. Gluconeogenesis is a mechanism that ensures that the brain has a supply of glucose when a diet is low in carbohydrates.

32. Conversion of glucose to other Carbohydrates (in animals) Conversion of glucose to other hexoses (isomers) and synthesis of di- or polysaccharides. Activation of glucose by Uridine Triphosphate (UTP) to form UDP-glucose. (Similar to ATP)

33. - - - - Enzyme Conversion of glucose to other Carbohydrates (in animals) Glycogenesis: conversion of glucose to glycogen. Exess glucose is stored in form of glycogen. Same process to produce di- and polysaccharides.

34. 2. Biosynthesis of Fatty acids Our body can produce all the fatty acids except essential fatty acids. Acetyl CoA Fatty acids synthesis: in cytoplasm Degeradation of fatty acids: in mitochondria They build up two C at a time. Excess food Acetyl CoAFatty acidsLipid (fat)

35. 2. Biosynthesis of Fatty acids ACP has a side chain that carries the growing fatty acid ACP rotates counterclockwise, and its side chain sweeps over the multienzyme system (empty spheres). Acyl Carrier Protein (ACP) At each enzyme, one reaction of chain is catalyzed.

36. 2. Biosynthesis of Fatty acids Step 1: ACP picks up an acetyl group from acetyl CoA and delivers to the first enzyme:

37. 2. Biosynthesis of Fatty acids Step 2: ACP-malonyltransferase reaction: Step 3: condensation reaction:

38. Step 4: the first reduction: Step 5: dehydration: 2. Biosynthesis of Fatty acids

39. Step 6: the second reduction: 2. Biosynthesis of Fatty acids One cycle of merry-go-round.

40. Maximum 16C (Palmitic acid). For 18C (Stearic acid) another system and enzyme. 2. Biosynthesis of Fatty acids Second cycle:

41. 3. Biosynthesis of Membrane Lipids 1- Glycerophospholipid 2- Cholesterol

42. 3. Biosynthesis of Membrane Lipids Glycerol 1-phosphate, which is obtained by reduction of dihydroxyacetone phosphate (from glycolysis). A vehicle for transporting electrons in and out of mitochondria.

43. 3. Biosynthesis of Membrane Lipids Fatty acids are activated by CoA, forming Fatty Acyl CoA. An amino alcohol is added to phosphate by phosphate ester bond. Is activated by CTP (like UTP but cytosine instead of uracil)

44. 3. Biosynthesis of Membrane Lipids Cholesterol is made of acetyl CoA (all of the C atoms). First reaction of three acetyl CoA to form the six-carbon compound 3-hydroxy-3-methylglutaryl CoA (HMG-CoA). -2CoA-SH -1CoA-SH In Liver

45. Mevalonate undergoes phosporylation and decarboxylation to give the C 5 compound, isopentenyl pyrophosphate. 3. Biosynthesis of Membrane Lipids -CO 2 ATP  ADP Building block

46. Isopentenyl pyrophosphate (C 5 ) is the building block for the synthesis of geranyl pyrophosphate (C 10 ) and farnesyl pyrophosphate (C 15 ). 3. Biosynthesis of Membrane Lipids

47. Two farnesyl pyrophosphate (C 15 ) units are joined to form squalene (C 30 ) and, in a series of at least 25 steps, squalene is converted to cholesterol (C 27 ).

48. 4. Biosynthesis of Amino Acids All 20 amino acids are found in a normal diet. Essential amino acids: cannot be synthesis in our body. Nonessential amino acids: can be synthesis in our body.

49. Most nonessential amino acids are synthesized from intermediates of either glycolysis or the citric acid cycle. 4. Biosynthesis of Amino Acids Amination and reduction Reverse of oxidative deamination reaction (degradation in catabolism).

50. 4. Biosynthesis of Amino Acids Glutamate in turn serves as an intermediate in the synthesis of several amino acids by the transfer of its amino group by transamination.