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Biochemistry

Explore the catabolic breakdown of carbohydrates, lipids, and proteins into energy and raw materials in this biochemistry chapter. Discover the processes of glycolysis, b-oxidation, and amino acid catabolism, and understand the energy yields and metabolic pathways involved.

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Biochemistry

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  1. Biochemistry Chapter 28 Specific Catabolic Pathways: Carbohydrate, Lipid, and Protein Metabolism

  2. Problem Sets • PS #1 • Sections 28.1 – 28.4 • # 2, 3, 5, 7, 8, 9, 10, 12, 15, 16, 18, 19 • PS #2 • Sections 28.5 – 27.10 • # 22, 23, 24, 27, 28, 29, 30, 31, 32, 33, 36, 39, 40

  3. 28.1 The Catabolic Pathways • Food serves two purposes • Provide energy • Provide raw materials • Must be broken down and absorbed first • Carbohydrates • Break down to monosaccharides • Used to build new oligo- and polysaccharides • Used to produce energy • Process is called glycolysis

  4. 28.1 The Catabolic Pathways • Lipids • Hydrolyzed to glycerol and fatty acids • Or hydrolyzed to monoglycerides • Used to build complex molecules • Used to produce energy • Process is called b-oxidation • Proteins • Hydrolyzed to amino acids • Used as building blocks for proteins • All converge to common catabolic pathway

  5. 28.2 Glycolysis • Breakdown of monosaccharides • Releases energy • ATP • NADH • Occurs in many steps • Lots of enzymes involved • Glucose  fructose  glyceraldehyde  pyruvate  acetyl CoA / lactate

  6. 28.2 Glycolysis (Activation) Step 1 Consumes energy ATP phosphorylates C-6 of glucose Produces glucose 6-phosphate Step 2 Isomerize to fructose 6-phosphate

  7. 28.2 Glycolysis (Activation) Step 3 Consumes energy Another ATP phosphorylates C-1 of fructose Produces fructose 1,6-bisphosphate These first three steps activate the monosaccharide in preparation for glycolysis

  8. 28.2 Glycolysis (2nd Stage) Step 4 Fructose 1,6-bisphosphate broken into 2 C3 fragments Products are in equilibrium Only glyceraldehyde 3-phosphate is used in glycolysis As glyceraldehyde 3-phosphate is used up, Lechatelier’s principle shifts the equilibrium toward the production of more

  9. 28.2 Glycolysis (3rd Stage) Step 5 Glyceraldehyde 3-phosphate oxidized H given to NAD+ Step 6 Phosphate on carbonyl group transferred to ADP Creates an ATP

  10. 28.2 Glycolysis (3rd Stage) Step 7 Step 8 Isomerize by moving Phosphate to C2 Dehydrate to form a double bond

  11. 28.2 Glycolysis (3rd Stage) Step 9 Payoff step! Phosphate is hydrolyzed Keto-enol tautomerization shifts double bond, producing pyruvate Remember…we produced two C3 fragments Back in step 4, so we actually get 2 ATPs at this point So far, we used 2 ATPs (steps 1 & 3) and produced 3 ATPs (steps 6 & 9) Feedback control – pyruvate kinase is inhibited by ATP and activated by AMP

  12. 28.2 Glycolysis (3rd Stage) Glycolysis occurs in cytoplasm No oxygen, reactions are anaerobic Step 10 – Some bacteria anaerobically decarboxylate pyruvate to make ethanol Step 11 – In the absence of oxygen, pyruvate is reduced to lactate. Lactic acid buildup can lead to muscle cramps! Steps 12 & 13 – Will lead us into the citric acid cycle Let’s save that for the next slide!

  13. 28.2 Glycolysis (CAC Entrance) Best way to do it – send pyruvate to the mitochondria CoA causes oxidative decarboxylation of pyruvate, producing acetyl CoA Catalyzed by enzymes along the inner membrane of the mitochondrion Thus…we enter the Citric Acid Cycle!

  14. 28.3 Energy Yield of Glycolysis • Glycolysis occurs in the cytoplasm, oxidative phosphorylation in mitochondria • NADH can’t cross outer membrane • Need to transport e- across membrane • Transport system in muscle and nerve cells generates 2 ATP per NADH in the cytoplasm • Transport system in heart and liver cells generates 3 ATP per NADH in the cytoplasm • Total of 36 ATPs produced

  15. 28.4 Glycerol Catabolism Hydrolyze fats to obtain glycerol Use ATP to make glycerol 1-phosphate (activation) NAD+ oxidizes it to dihydroxyacetone phosphate Isomerized to glyceraldehyde 3-phosphate, enter glycolysis pathway at step 5.

  16. 28.5 b-Oxidation of Fatty Acids • Fatty acids degraded into two-carbon units (acetate) by oxidation of the b carbon • Fatty acid is activated by attaching a CoA • Occurs in the cytosol • Enzymes transfer the acyl CoA across the membrane into the mitochondrion, where it can be oxidized

  17. 28.5 b-Oxidation of Fatty Acids

  18. 28.6 Energy Yield from Fats • Activation: ATP  AMP + 2 Pi • Equivalent to using 2 ATP molecules • Each cycle of the b-oxidation spiral: • One FADH2, one NADH + H+, one acetyl CoA • Last cycle produces one FADH2 • Conversion to ATP: • FADH2 2 ATP, NADH  3 ATP, acetyl CoA  12 ATP • For steric acid (C18), total of 146 ATP • 8.1 ATP molecules per C atom • Glucose  36 ATP, which is 6 ATP per C atom

  19. 28.7 Ketone Bodies • Normally metabolize glucose in preference of fats; fats are stored in the cells • Low glucose levels activate b-oxidation • Low glucose also slows the CAC because of a lack of oxaloacetate precursors • Break down fats to acetyl CoA, but the CAC can’t keep up with the supply • Liver converts Acetyl CoA into ketones

  20. 28.7 Ketone Bodies

  21. 28.8 Amino Acid Catabolism • Proteins broken down into amino acids • Amino acids used to make new proteins • Excess amino acids can’t be stored • Must be catabolized for enegy • Nitrogen in the NH2 group is a problem • Catabolized in the liver in 3 steps • Transamination • Oxidative deamination • The urea cycle

  22. 28.8 Transamination Amino acids transfer amino groups to a-ketoglutarate Forms glutamate Carbon skeleton remains behind as an a-ketoacid We’ll take care of that later

  23. 28.8 Oxidative deamination Occurs in the mitochondrion Amino group is removed, regenerating a-ketoglutarate Yields NADH + H+, which is used to produce 3 ATPs N is released as NH4+, which needs to be disposed of

  24. 28.8 The Urea Cycle NH4+ is converted to urea so it can be excreted

  25. 28.8 Urea Cycle Step 1 Occurs in the mitochondrion NH4+ combines with CO2 to form carbamoyl phosphate Costs 2 ATP, so this better be worth it!

  26. 28.8 Urea Cycle Step 2 Carbamoyl phosphate is combined with ornithine Ornithine is a basic amino acid not used in proteins Product is citrulline, which diffuses out of the mitochondrion

  27. 28.8 Urea Cycle Step 3 Occurs in the cytoplasm Citrulline combines with aspartate, forming argininosuccinate Energy provided by hydrolyzing ATP  AMP + PPi

  28. 28.8 Urea Cycle Step 4 Argininosuccinate is split into arginine and fumarate

  29. 28.8 Urea Cycle Step 5 Arginine is hydrolyzed to urea an ornithine Ornithine goes back to the beginning of the cycle Urea is excreted in the urine

  30. 28.8 Urea Cycle • Carbamoyl phosphate is important because it is used for the synthesis of nucleotide bases • Urea cycle and CAC are linked because both involve fumarate • Not all organisms excrete N as urea • Bacteria and fish excrete ammonia directly • Birds and reptile excrete uric acid

  31. 28.9 Carbon Skeletons of AAs • We promised to talk about the fate of the carbon skeleton of amino acids after oxidative deamination • They follow multiple pathways, depending on the specific carbon chain • Some degrade to glucose precursors like pyruvate – glucogenic amino acids • Others form ketone bodies – ketogenic

  32. 28.10 Heme Catabolism • RBCs are destroyed by phagocytic cells • Hemoglobin must be metabolized • Globin is hydrolyzed to amino acids • Heme is oxidized to biliverdin and bilirubin

  33. Summary of Catabolism

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