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Combined Chapters Carbohydrate, Lipid, and Protein Metabolism Stage 1: Digestion of Carbohydrates • In the mouth, salivary amylase hydrolyzes aglycosidic bonds in polysaccharides to give smaller polysaccharides (dextrins), maltose, and some glucose. • In the small intestine, pancreatic amylase hydrolyzes dextrins to maltose and glucose. • The disaccharides maltose, lactose, and sucrose are hydrolyzed to monosaccharides. • The monosaccharides enter the bloodstream for transport to the cells. Metabolism | # 2 Summary of carbohydrate digestion in the human body. Metabolism | # 3 Metabolism Section of the small intestine, showing its folds and the villi that cover the inner surface of the folds. © Ed Reschke / Peter Arnold, Inc. Metabolism | # 4 Glycolysis: Splitting Sugar • In Stage 2, the metabolic pathway called glycolysis degrades glucose (6C) obtained from digestion to pyruvate (3C) Metabolism | # 5 Glycolysis: Energy-Investment In reactions 1-5 of glycolysis: • Energy is used to add phosphate groups to glucose and fructose • Glucose is converted to two three-carbon molecules Metabolism | # 6 Glycolysis: Energy-Production • In reactions 7 and 10, the hydrolysis of triose phosphates generates four ATP molecules Metabolism | # 7 Step 1: Formation of Glucose 6-phosphate Step 2: Formation of Fructose 6-Phosphate O OH ATP ADP O H H H H HO P O O H OH H H H HO OH OH Hexokinase H HO OH Step 1 H OH OH OH O HO Step 2 P O O O H OH H H H H HO HO P O OH O H HO OH OH OH OH OH H phosphoglucoisomerase OH H Metabolism | # 8 Step 3: Formation of Fructose 1,6-bisphosphate Step 4: Formation of Triose Phosphates ATP O Step 3 HO O P P OH 6 5 C H 4 O P H HO C C OH H OH 3 O OH 2 C OH HO Aldolase O CH2 P OH H O O 1 P OH H OH H2C C 2 O O H HO H H2C O O phosphofructokinase O O P O OH OH OH HO HO O H HO H 1 O OH OH O ADP OH 4 CH 5 HC OH + H2C 6 OH O O P Step 4 OH OH 3 Metabolism | # 9 OH Step 5: Isomerization of Triose Phosphates Step 5 O H2C C HO O O CH2 P OH OH + O O CH CH HC OH O H2C O P OH 2 OH Triosephosphate isomerase HC OH O H2C O P OH OH By the end of Step 5, we have: 1. Used two molecules of ATP so we can 2. Break Glucose (6C) into 2 3C units of glyceraldehyde 3-phosphate Metabolism | # 10 Step 6: Formation of 1,3-Bisphosphoglycerate Step 7: Formation of 3-Phosphoglycerate Step 6 + 2NAD+ +2Pi 2 2 + 2NADH + 2H+ Glyceraldehyde 3-phosphate dehydrogenase Step 7 O O O P OH OH 2 O 2ADP 2ATP OH 2 O O P OH OH O- phosphoglycerokinase OH O O P OH OH Metabolism | # 11 Step 8: Formation of 2-Phosphoglycerate Step 9: Formation of Phosphoenolpyruvate O O- O OC 2 OH O O P 2 OH phosphoglyceromutas e OH O 2 O P HC H2C OH O O O P OH OC OH 2 OH H2C Step 8 OH OH OC Step 9 HC O enolase C O O P OH OH HC H +2H2O Metabolism | # 12 Step 10: Formation of Pyruvate O OC 2 C O O P OH HC 2ADP H O 2ATP C 2 OH pyruvate kinase O- C O CH3 By the end of Step 10, we have: 1. Generated 4 ATP molecules (2 net) Metabolism | # 13 Glycolysis: Overall Reaction • Glycolysis generates 2 ATP and 2 NADH • Two ATP are used in energy-investment to add phosphate groups to glucose and fructose-6-phosphate • Four ATP are formed in energy-generation by direct transfers of phosphate groups to four ADP. Glucose + 2ADP + 2Pi + 2NAD+ 2Pyruvate + 2ATP + 2NADH + 4H+ Metabolism | # 14 Metabolism Metabolism | # 15 Regulation of Glycolysis • Reaction 1 Hexokinase is inhibited by high levels of glucose-6-phosphate (feedback) • Reaction 3 Phosphofructokinase, an allosteric enzyme, is inhibited by high levels of ATP and activated by high levels of ADP and AMP • Reaction 10 Pyruvate kinase, another allosteric enzyme is inhibited by high levels of ATP or acetyl CoA Metabolism | # 16 Pathways for Pyruvate When oxygen is present in the cell, pyruvate from glycolysis is decarboxylated to produce acetyl CoA (enters TCA cycle) and CO2 • Pyruvate + HS-CoA + NAD+ acetyl CoA + CO2 + NADH + H+ Metabolism | # 17 Lactate Formation When oxygen is not available, pyruvate is reduced to lactate, which replenishes NAD+ to continue glycolysis • Pyruvate + NADH + H+ lactate + NAD+ Metabolism | # 18 Lactate in Muscles Under anaerobic conditions (strenuous exercise): • Oxygen in the muscles is depleted • Lactate accumulates in the muscles • Muscles tire and become painful • Rest is needed to repay the oxygen debt and to reform pyruvate in the liver Metabolism | # 19 Fermentation Fermentation: • Occurs in anaeobic microorganisms such as yeast • Decarboxylates pyruvate to acetaldehyde, which is reduced to ethanol. • Regenerates NAD+ to continue glycolysis • Pyruvate + NADH + H+ ethanol + NAD+ + CO2 Metabolism | # 20 All three of the common fates of pyruvate from glycolysis provide for the regeneration of NAD+ from NADH. Metabolism | # 21 Metabolism Structural relationships among glycerol and acetone and the C3 intermediates. Metabolism | # 22 Metabolism Entry points for fructose and galactose into the glycolysis pathway. Metabolism | # 23 Metabolism The dihyroxyacetone phosphate-glycerol 3phosphate shuttle. Cytosolic NADH can not cross mitochondrial membrane. Shuttle brings cytosolic electrons into mitochondria in form of mitochondrial FADH2 Metabolism | # 24 Metabolism The processes of glycogenesis, storage of glucose and glycogenolysis, liberating glucose, are contrasted. Metabolism | # 25 Metabolism The Cori Cycle Metabolism | # 26 Metabolism Metabolism | # 27 Metabolism Saturn Stills / SPL / Photo Researchers A diabetic giving himself a blood glucose test. Metabolism | # 28 Metabolism The events that must occur before triacylglycerols can reach the bloodstream through the digestive process. Metabolism | # 29 Metabolism Chylomicron, a type of lipoprotein Metabolism | # 30 Metabolism Structural characteristics of the adipose cell. Metabolism | # 31 Metabolism Fatty acids are transported across the inner mitochondrial membrane in the form of acyl carnitine. Metabolism | # 32 Reactions of the fatty acid spiral for an 18:0 fatty acid. Metabolism | # 33 Lipids cont’d Metabolism | # 34 Metabolism Summary of protein digestion in human body. Metabolism | # 35 Metabolism Metabolism | # 36 Metabolism Possible fates for amino acid degradation products. Metabolism | # 37 Metabolism Key compounds in the transamination / oxidative deamination process include three keto acid/amino acid pairs. Metabolism | # 38 The fourstep urea cycle. Metabolism | # 39 Metabolism Fates of the carbon skeletons of amino acids. Metabolism | # 40 Metabolism The starting materials for the biosynthesis of the 11 nonessential amino acids. Metabolism | # 41 Metabolism | # 42 Human body response to feasting, fasting, and starving. Metabolism | # 43