Biochemistry

1. Biochemistry Chapter 29 Making Methamphetamine

2. Biochemistry Chapter 29 Biosynthetic Pathways

3. Problem Sets • PS #1 • Sections 29.1 – 29.2 • # 1, 2, 3, 4, 6, 7, 8, 9, 10, 12, 13 • PS #2 • Sections 29.3 – 29.5 • # 14, 15, 18, 24, 26, 28, 29, 31, 33

4. 29.1 Overview of Biosynthesis • Anabolism (biosynthesis) occurs via different pathways from catabolism • Provides flexibility – if one pathway is blocked, the other can be reversed • Overcomes LeChatelier’s principle • In glycolysis, excess phosphate drives the equilibrium toward degradation of glucose rather than formation • Using a different pathway eliminates the need to reverse the equilibrium

5. 29.2 Biosynthesis of Carbohydrates • Photosynthesis • Conversion of atmospheric CO2 to glucose in plants • Gluconeogenesis • Synthesis of glucose in animals • Glycogenesis • Conversion of glucose into other carbohydrates in animals

6. 29.2 Photosynthesis • Energy from the sun (photons) built into the chemical bonds of carbohydrates • 6 H2O + 6 CO2 C6H12O6 + 6 O2 • Occurs in chloroplasts, which have a similar structure to mitochondria • Process uses large protein-cofactor complexes (photosystem I, II, and III) • Most glucose in plants is converted to cellulose or starch

7. 29.2 Photosynthesis Chloroplast

8. 29.2 Photosynthesis

9. 29.2 Photosynthesis • Light reactions • Chlorophyl uses solar photons to strip electrons and protons from water • H2O + ADP + Pi + NADP+ + sunlight  ½ O2 + ATP + NADPH + H+ • Dark reactions • Convert CO2 to carbohydrates • CO2 + ATP + NADPH + H+ (CH2O)n + ADP + Pi + NADP+ • Energy from light reactions stored in carbohydrates

10. 29.2 Gluconeogenesis • Glucose is synthesized from intermediates from the glycolysis pathway and the CAC • Pyruvate, lactate, oxaloacetate, malate, glucogenic amino acids • Proceeds in reverse order from glycolysis • Uses many of the same enzymes • 4 unique enzymes make it a different pathway • Uses ATP instead of producing it • Cori cycle – use of lactate from anaerobic glycolysis to produce glucose

11. 29.2 Gluconeogenesis

12. 29.2 The Cori Cycle Relative NAD+ and NADH concentrations drive the direction of the equilibrium

13. 29.2 Glycogenesis • Conversion of glucose to other sugars • Other hexoses • Hexose derivatives • Di-, oligo-, or polysaccharides • First step – activation of glucose by UTP

14. 29.2 Glycogenesis Synthesis of di- and polysaccharides

15. 29.3 Biosynthesis of Fatty Acids • Humans can synthesize all needed fatty acids except linoleic acid and linolenic acid • Builds fatty acids from acetyl CoA groups • Not the reverse of b-oxidation • Occurs in cytoplasm rather than mitochondria • Uses a multienzyme system • Synthesized when excess energy is available, stored in specialized cells

16. 29.3 Biosynthesis of Fatty Acids • Acyl Carrier Protein (ACP) bonds to growing fatty acid chain • Rotates counterclockwise, sweeping fatty acid chain over a series of enzymes • Each rotation adds one acetyl group

17. 29.3 Biosynthesis of Fatty Acids ACP takes an acetyl group from CoA Transfers it to the first enzyme, fatty acid synthase ACP brings in a C3 group. Combine and decarboxylate

18. 29.3 Biosynthesis of Fatty Acids • We now have a C4 chain on the ACP • Reduce and dehydrate to get rid of the double bond; it’s now a C4 fatty acid • Do another rotation to get it up to a C6 • ACP can do this up to C16 • Beyond that, a different enzyme system is used to add to palmitic acid

19. 29.3 Biosynthesis of Fatty Acids • Unsaturated fatty acids go through an additional oxidation step • Hydrogen is removed and combined with oxygen to make water

20. 29.4 Biosynthesis of Phospholipids • Reduce dihydroxyacetone phosphate to glycerol 3-phosphate • Add two acyl CoA molecules

21. 29.4 Biosynthesis of Phospholipids • Add serine, choline, or ethanolamine to the phosphate group • Activate with cytidine triphosphate (CTP) • Sphingolipiods start with production of a ceramide • Activated phosphocholine is added to the sphingosine to make sphingomyelin • Glycolipids are made by adding UDP-glucose units one at a time

22. 29.4 Biosynthesis of Cholesterol • Synthesized in the liver from acetyl CoA • LDLs can’t cross the blood-brain barrier; the brain has to make its own cholesterol • Synthesized in the nerve cells for use in synapses

23. 29.4 Biosynthesis of Cholesterol Start by making 3-hydroxy-3-methylglutaryl CoA (HMGCoA) by combining 3 acetyl CoA molecules HMG reductase removes the CoA and reduces the thioester to a primary alcohol to make mevalonate Mevalonate is decaboxylated and phosphorylated to make the C5 compound isopentyl pyrophosphate

24. 29.4 Biosynthesis of Cholesterol Isopentyl pyrophosphates are combined to make C10 and C15 units (farnesyl pyrophosphate) Cholesterol is synthesized by combining two farnesyl pyrophosphate units Statin drugs are competitive inhibitors of HMG reductase Geranyl pyrophosphate and farnesyl pyrophosphate are also used to make proteins nonpolar so they can interact with the cell membrane (prenylation)

25. 29.5 Biosynthesis of Amino Acids Some amino acids cannot be synthesized (essential amino acids) Others can be synthesized (nonessential) from intermediates of glycolysis or CAC Synthesize glutamate from a-ketoglutarate This is just the oxidative deamination reaction done in reverse

26. 29.5 Biosynthesis of Amino Acids Glutamate is used to synthesize alanine, serine, aspartate, asparagine, and glutamate by transamination Amino acids are used to synthesize other biomolecules Serine is used to synthesize membrane lipids Heme, purines, and pyrimidines are synthesized from amino acids