Chapter 21 Biosynthetic Pathways Chemistry 20

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

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

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.

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

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

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

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.

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

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

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)

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.

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)

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.

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

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

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

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

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

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

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.

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)

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

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

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

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 ).

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.

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).

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.