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Che 214 lecture 04

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Che 214 lecture 04

  1. 1. CHE 214: Biochemistry Lecture Three •BIOENERGETICSLecturer: Dr. G. Kattam Maiyoh GKM/CHE 214/LEC 04/SEM 02/2013
  2. 2. The Brain Will Make Ketone Bodies If It’s Starving ForGlucose Acetyl-CoA Acetoacetyl CoA synthase HMG CoA synthase HMG CoAlyase GKM/MLS2119/LEC 05/SEM 02/2013
  3. 3. Ketosis• Blood ketone levels are usually very low – many tissues use ketone bodies for ATP production• Fasting, starving or high fat meal with few carbohydrates results in excessive beta oxidation & ketone production – acidosis (ketoacidosis) is abnormally low blood pH – sweet smell of ketone body acetone on breath – occurs in diabetic since triglycerides are used for ATP production instead of glucose & insulin inhibits lipolysis GKM/CHE 214/LEC 04/SEM 02/2013 25-3
  4. 4. The Brain WillUse AminoAcidsTo MakeGlucose If ItHas To GKM/MLS2119/LEC 05/SEM 02/2013
  5. 5. Gluconeogenesis: Synthesis Of Glucose From PyruvateGluconeogenesis is not just glycolysis in reverse--the enzymes in green print catalyze irreversible reactionsIt requires cleavage of 6 phosphoanhydride bonds to synthesize one molecule of glucose from pyruvate-- 4 from ATP and 2 from GTP GKM/MLS2119/LEC 05/SEM 02/2013
  6. 6. Your Body has Several Sources of PyruvateLactate from anaerobic respiration (ex. red blood cells,working skeletalmuscle)Amino acid breakdownGlycerol from triglyceride breakdown GKM/MLS2119/LEC 05/SEM 02/2013
  7. 7. Phosphofructokinase and Fructose-1,6- Bisphosphate are Glucose -6- phosphataseReciprocally Controlled This is the primary means by which the balance between glycolysis and gluconeogenesis is maintained PFK is stimulated and F-1,6-B is inhibited by NAD+, ADP, and AMP NADH and ATP have the opposite effects GKM/MLS2119/LEC 05/SEM 02/2013
  8. 8. Glucose-6-PhosphataseTakes the PhosphateGroup off Glucose-6- Glucose -6- phosphatasePhosphate to MakeGlucose GKM/MLS2119/LEC 05/SEM 02/2013
  9. 9. Glycogenesis—Storing The Energy for LaterMonosaccharides are activated bylinking them todiphosphonucleotidesEx. Glucose  glucose-6-Pglucose-6-p  glucose-1-pGlucose-1-phosphate + UTP  UDP-glucose + PPiUTP is uracil triphosphate—anotherphosphorylated nucleotide like ATP GKM/MLS2119/LEC 05/SEM 02/2013
  10. 10. Glycogenesis—Storing the Energy for Later The activated glucoses are chained together to make the backbone of glycogen by glycogen synthase—it makes alpha-1,4 O-glycosidic bonds The glycogen branching enzyme makes the alpha-1,6 linkages that allow branches to develop, making glycogen highly branched GKM/MLS2119/LEC 05/SEM 02/2013
  11. 11. Glycogenesis & Glycogenolysis• Glycogenesis – glucose storage as glycogen – 4 steps to glycogen formation in liver or skeletal muscle – stimulated by insulin• Glycogenolysis – glucose release is not a simple reversal of steps – enzyme phosphorylase splits off a glucose molecule by phosphorylation to form glucose 1-phosphate – The enzyme is only in hepatocytes so muscle can’t release glucose – It is activated by glucagon 214/LEC 04/SEM 02/2013 epinephrine (adrenal) GKM/CHE (pancreas) & GKM/CHE 214/LEC 03/SEM 02/2011 25-11
  12. 12. Gluconeogenesis• Liver glycogen runs low if fasting, starving or not eating carbohydrates forcing formation from other substances – lactic acid, glycerol & certain amino• Stimulated by cortisol (adrenal) & glucagon (pancreas) – cortisol stimulates breakdown of proteins freeing amino acids – thyroid mobilizes triglycerides from adipose tissue GKM/CHE 214/LEC 03/SEM 02/2011 04/SEM 02/2013 25-12
  13. 13. Transport of Lipids by Lipoproteins• Most lipids are nonpolar and must be combined with protein to be tranported in blood• Lipoproteins are spheres containing hundreds of molecules – outer shell polar proteins (apoproteins) & phospholipids – inner core of triglyceride & cholesterol esters• Lipoprotein are categorized by function & density• 4 major classes of lipoproteins – chylomicrons, very low-density, low-density & high-density lipoproteins GKM/CHE 214/LEC 03/SEM GKM/CHE 214/LEC 04/SEM 02/2013 02/2011 25-13
  14. 14. Classes of Lipoproteins• Chylomicrons (2 % protein) – form in intestinal epithelial cells to transport dietary fat • apo C-2 activates enzyme that releases the fatty acids from the chylomicron for absorption by adipose & muscle cells • liver processes what is left• VLDLs (10% protein) – transport triglycerides formed in liver to fat cells• LDLs (25% protein) --- “bad cholesterol” – carry 75% of blood cholesterol to body cells – apo B100 is docking protein for receptor-mediated endocytosis of the LDL into a body cell • if cells have insufficient receptors, remains in blood and more likely to deposit cholesterol in artery walls (plaque)• HDLs (40% protein) --- “good cholesterol” – carry cholesterol from cells to liver for elimination GKM/CHE 214/LEC 03/SEM GKM/CHE 214/LEC 04/SEM 02/2013 02/2011 25-14
  15. 15. Blood Cholesterol• Sources of cholesterol in the body – food (eggs, dairy, organ meats, meat) – synthesized by the liver• All fatty foods still raise blood cholesterol – liver uses them to create cholesterol – stimulate reuptake of cholesterol containing bile normally lost in the feces• Desirable readings for adults – total cholesterol under 200 mg/dL; triglycerides 10-190 mg/dL – LDL under 130 mg/dL; HDL over 40 mg/dL – cholesterol/HDL ratio above 4 is undesirable risk• Raising HDL & lowering cholesterol can be accomplished by exercise, diet & drugs GKM/CHE 214/LEC 03/SEM GKM/CHE 214/LEC 04/SEM 02/2013 02/2011 25-15
  16. 16. Fate of Lipids• Oxidized to produce ATP• Excess stored in adipose tissue or liver• Synthesize structural or other important molecules e.g. – phospholipids of plasma membranes – lipoproteins that transport cholesterol – thromboplastin for blood clotting – myelin sheaths to speed up nerve conduction – cholesterol used to synthesize bile salts and steroid hormones.GKM/CHE 214/LEC 03/SEM GKM/CHE 214/LEC 04/SEM 02/201302/2011 25-16
  17. 17. Triglyceride Storage• Adipose tissue removes triglycerides from chylomicrons and VLDL and stores it. – 50% subcutaneous, 12% near kidneys, 15% in omenta, 15% in genital area, 8% between muscles• Fats in adipose tissue are ever-changing – released, transported & deposited in other adipose• Triglycerides store more easily than glycogen – do not exert osmotic pressure on cell membranes – are hydrophobicGKM/CHE 214/LEC 03/SEM GKM/CHE 214/LEC 04/SEM 02/201302/2011 25-17
  18. 18. Lipid Catabolism: Lipolysis• Triglycerides are split into fatty acids & glycerol by lipase – glycerol • if cell ATP levels are high, converted into glucose • if cell ATP levels are low, converted into pyruvic acid which enters aerobic pathway to ATP production GKM/CHE 214/LEC 03/SEM 02/2011 04/SEM 02/2013 25-18
  19. 19. Lipolysis & Fatty acids Liver cells• Beta oxidation in mitochondria removes 2 carbon units from fatty acid & forms acetyl coenzyme A• Liver cells form acetoacetic acid from 2 carbon units & ketone bodies from acetoacetic acid (ketogenesis) – heart muscle & kidney cortex prefer to use acetoacetic acid for ATP production GKM/CHE 214/LEC 03/SEM 02/2011 04/SEM 02/2013 25-19
  20. 20. Lipid Anabolism: Lipogenesis• Synthesis of lipids by liver cells = lipogenesis – from amino acids • converted to acetyl CoA & then to triglycerides – from glucose • from glyceraldehyde 3-phosphate to triglycerides• Stimulated by insulin when we eat excess calories GKM/CHE 214/LEC 04/SEM 02/2013 25-20