Chapter 21 Biosynthetic Pathways

1. Chemistry 20 Chapter 21 Biosynthetic Pathways

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

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. Catabolic Simple Molecules Complex Molecule Biosynthetic

4. Biosynthetic pathways 2. Overcoming Le Chatelier’s principle: 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 Mitochondria Anabolic reactions Cytoplasm

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

7. (from sun) 1. Biosynthesis of Carbohydrates In plants 6CO2 Photosynthesis

8. 1. Biosynthesis of Carbohydrates In animals When energy is not needed, 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.

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

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

11. 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)

12. - - - - 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.

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

14. 2. Biosynthesis of Fatty acids Acyl Carrier Protein (ACP) 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). At each enzyme, one reaction of chain is catalyzed.

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

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

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

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

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

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

21. 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.

22. 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)

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

24. 3. Biosynthesis of Membrane Lipids Mevalonate undergoes phosporylation and decarboxylation to give the C5 compound, isopentenyl pyrophosphate. ATP  ADP -CO2 Building block

25. 3. Biosynthesis of Membrane Lipids Isopentenyl pyrophosphate (C5) is the building block for the synthesis of geranyl pyrophosphate (C10) and farnesyl pyrophosphate (C15).

26. 3. Biosynthesis of Membrane Lipids Two farnesyl pyrophosphate (C15) units are joined to form squalene (C30) and, in a series of at least 25 steps, squalene is converted to cholesterol (C27).

27. 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.

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

29. 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.