* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Oxidation
Proteolysis wikipedia , lookup
Peptide synthesis wikipedia , lookup
Basal metabolic rate wikipedia , lookup
Photosynthesis wikipedia , lookup
Evolution of metal ions in biological systems wikipedia , lookup
Genetic code wikipedia , lookup
Photosynthetic reaction centre wikipedia , lookup
Butyric acid wikipedia , lookup
Microbial metabolism wikipedia , lookup
Metalloprotein wikipedia , lookup
Oxidative phosphorylation wikipedia , lookup
Adenosine triphosphate wikipedia , lookup
Nicotinamide adenine dinucleotide wikipedia , lookup
Lactate dehydrogenase wikipedia , lookup
Fatty acid synthesis wikipedia , lookup
Glyceroneogenesis wikipedia , lookup
Amino acid synthesis wikipedia , lookup
Fatty acid metabolism wikipedia , lookup
Biosynthesis wikipedia , lookup
Biochemistry wikipedia , lookup
Frederick A. Bettelheim William H. Brown Mary K. Campbell Shawn O. Farrell www.cengage.com/chemistry/bettelheim Chapter 28 Specific Catabolic Pathways: Carbohydrate, Lipid, and Protein Metabolism William H. Brown • Beloit College Convergence of Pathways • Figure 28.2 Convergence of the specific pathways of carbohydrate fat, and protein catabolism into the common pathway. 28-2 Glycolysis Glycolysis: A series of 10 enzyme-catalyzed reactions by which glucose is oxidized to two molecules of pyruvate. C6 H1 2 O6 Glucos e glycolys is O 2 CH3 CCOO - + 2 H+ Pyruvate • During glycolysis, there is net conversion of 2ADP to 2ATP. C6 H1 2 O6 + 2 ADP + 2 Pi Glucose O 2 CH3 CCOO - + 2 ATP Pyruvate 28-3 Glycolysis • Reaction 1: Phosphorylation of -D-glucose. HO HO CH2 OH O O O + -O-P-O-P-O-AMP OH -D -Glucose OH HO HO - O - O ATP CH 2 OPO3 O hexokinas e 2+ Mg 2- OH OH -D -Glucose 6-p hosphate O + - O-P-O-AMP O ADP 28-4 Glycolysis • Reaction 2: Isomerization of glucose 6-phosphate to fructose 6-phosphate. 6 2- 6 2- CH2 OPO3 CH2 OPO3 1 ph os phohexose CH2 OH O O HO isomeras e H HO 2 HO 2 1 H OH OH OH HO H -D-Glu cose 6-phosp hate -D -Fru ctos e 6-phosp hate 28-5 Glycolysis This isomerization is most easily seen by considering the open-chain forms of each monosaccharide. It is one ketoenol tautomerism followed by another. 1 CHO H 2 OH HO H H OH H OH CH2 OPO3 2 Glucose 6-p hos phate H C OH C OH HO H H OH H OH CH2 OPO3 2(A n ened iol) 1 CH2 OH 2C O HO H H OH H OH CH2 OPO3 2 Fru ctose 6-phosp hate 28-6 Glycolysis • Reaction 3: Phosphorylation of fructose 6-phosphate. 6 CH2 OPO 3 2 - 1 CH2 OH O H HO + A TP H OH HO H -D-Fructose 6-phosphate phosphofructokinase Mg 2 + 6 CH2 OPO 3 2 - 1 CH2 OPO 3 2 O H HO + A DP H OH HO H -D-Fructose 1,6-bisphosphate 28-7 Glycolysis • Reaction 4: Cleavage of fructose 1,6-bisphosphate to two triose phosphates. CH2 OPO3 2- C=O HO H H al dol ase H OH OH CH2 OPO3 2 - Fructose 1,6-b isph osp hate CH2 OPO3 2 C=O CH2 OH CHO H C OH CH2 OPO3 2 - D ih yd roxyacetone p hos phate D -Glyceraldehyde 3-p hosph ate 28-8 Glycolysis • Reaction 5: Isomerization of triose phosphates. • Catalyzed by phosphotriose isomerase. • Only the D enantiomer of glyceraldehyde 3-phosphate is formed. CH2 OH CHO H C OH C=O CH2 OPO3 2- D ih yd roxyaceton e ph os phate CH2 OPO3 2- D-Glyceraldehyde 3-p hosph ate 28-9 Glycolysis Reaction 6: Oxidation of the -CHO group of Dglyceraldehyde 3-phosphate. • The product contains a phosphate ester and a highenergy mixed carboxylic-phosphoric anhydride. CHO H C OH 2CH2 OPO3 D -Glyceraldehyde 3-ph os phate + + NAD + Pi glyceraldeh yd e 3-p hosphate d ehydrogenase O 2C-OPO3 H C OH + NADH 2CH2 OPO3 1,3-Bis phosp hoglycerate 28-10 Glycolysis Reaction 7: Transfer of a phosphate group from 1,3bisphosphoglycerate to ADP. O 2C-OPO3 + H C OH CH2 OPO3 2 1,3-Bisp hos phoglycerate O O-P-O-AMP O- phosp hoglycerate kinas e Mg 2 + AD P COOO O + -O-P-O-P-O-AMP H C OH O O CH2 OPO3 2 3-Ph os phoglycerate ATP 28-11 Glycolysis Reaction 8: Isomerization of 3-phosphoglycerate to 2phosphoglycerate. phosph oglycerate COOCOOmutas e H C OH H C OPO3 2 CH2 OH CH2 OPO3 22-Ph os phoglycerate 3-Phos phoglycerate Reaction 9: Dehydration of 2-phosphoglycerate. COOCOOen olase 22+ H2 O H C OPO3 C OPO 2+ 3 Mg CH2 OH CH2 2-Phosph oglycerate Phosph oen olp yruvate 28-12 Glycolysis Reaction 10: Phosphate transfer to ADP. - COO O 2C OPO3 + O-P-O-AMP CH2 OPh os phoenolpyruvate pyru vate kinas e Mg2 + AD P O O COOC=O + O-P-O-P-O-AMP O- OCH3 A TP Pyruvate 28-13 Glycolysis Summing these 10 reactions gives the net equation for glycolysis: C6 H1 2 O6 + 2 N A D+ + 2 HPO 4 2 - + 2 A DP Glucos e O 2 CH3 CCOO - + 2 NADH + Pyruvate glycolys is 2 ATP + 2 H 2 O + 2 H + 28-14 Reactions of Pyruvate Pyruvate is most commonly metabolized in one of three ways, depending on the type of organism and the presence or absence of O2. 12 aerobic conditions p lants and animals Acetyl CoA 13 Citric acid cycle OH O - 11 anaerob ic conditions CH3 CHCOOCH3 CCOO contracting mu scle Lactate Pyruvate 10 anaerob ic conditions CH3 CH2 OH + CO2 fermentation in yeast Ethanol 28-15 Reactions of Pyruvate A key to understanding the biochemical logic behind two of these reactions of pyruvate is to recognize that glycolysis needs a continuing supply of NAD+. • if no oxygen is present to reoxidize NADH to NAD+, then another way must be found to reoxidize. 28-16 Pyruvate to Lactate • In vertebrates under anaerobic conditions, the most important pathway for the regeneration of NAD+ is reduction of pyruvate to lactate. Pyruvate, the oxidizing agent, is reduced to lactate. lactate O dehydrogenase + CH3 CCOO + NA DH + H Pyruvate OH CH3 CHCOO- + NA D+ Lactate • Lactate dehydrogenase (LDH) is a tetrameric isoenzyme consisting of H and M subunits; H4 predominates in heart muscle, M4 in skeletal muscle. 28-17 Pyruvate to Lactate • While reduction to lactate allows glycolysis to continue, it increases the concentration of lactate and also of H+ in muscle tissue. C6 H1 2 O6 Glucos e lactate fermentation OH 2 CH3 CHCOO- + 2 H+ Lactate • When blood lactate reaches about 0.4 mg/100 mL, muscle tissue becomes almost completely exhausted. 28-18 Pyruvate to Ethanol Yeasts and several other organisms regenerate NAD+ by this two-step pathway: • Decarboxylation of pyruvate to acetaldehyde. pyruvate O decarboxylase + CH3 CCOO + H Pyruvate O CH3 CH + CO 2 Acetaldehyde • Acetaldehyde is then reduced to ethanol. NADH is the reducing agent. Acetaldehyde is oxidized and is the reducing agent in this redox reaction. alcohol O dehydrogenase + CH3 CH + N AD H + H Acetaldehyde CH3 CH2 OH + NA D + Ethanol 28-19 Pyruvate to Acetyl-CoA • Under aerobic conditions, pyruvate undergoes oxidative decarboxylation. • The carboxylate group is converted to CO2. • The remaining two carbons are converted to the acetyl group of acetyl CoA. • This reaction provides entrance to the citric acid cycle. oxidative O decarboxylation CH3 CCOO - + NAD+ + CoASH Pyruvate O CH3 CSCoA + CO2 + N ADH Acetyl-CoA 28-20 Pentose Phosphate Pathway • Figure 28.5 Simplified schematic representation of the pentose phosphate pathway, also called a shunt. 28-21 Energy Yield in Glycolysis Step 1, 2, 3 Reaction(s) Activation (glucose fru ctose 1,6-bisp hosphate ATP prod uced 5 Ph os phorylation 2 (glyceraldeh yd e 3-phosph ate 1,3-bis phosph oglycerate), produces 2(N AD + + H+ ) in cytosol 4 6, 9 Ph os phate transfer to A DP from 1,3-bisph os phoglycerate and phosph oen olp yruvate 4 12 Oxidative decarboxylation 2 (pyruvate acetyl CoA), produces 2(N AD + + H + ) 6 13 Oxidation to tw o acetyl CoA in th e citric acid cycle etc. TOTAL -2 24 36 28-22 Catabolism of Glycerol • Glycerol enters glycolysis via dihydroxyacetone phosphate. CH2 OH ATP CHOH CH2 OH Glycerol ADP + NAD CH2 OH CHOH CH2 OPO3 2Glycerol 1-phosph ate NADH CH2 OH C=O CH2 OPO3 2 D ihydroxyacetone phosp hate 28-23 Fatty Acids and Energy Fatty acids in triglycerides are the principal storage form of energy for most organisms. • Hydrocarbon chains are a highly reduced form of carbon. • The energy yield per gram of fatty acid oxidized is greater than that per gram of carbohydrate oxidized. Energy Energy -1 (k cal• mol ) (kcal• g -1) C6 H1 2 O6 + 6 O2 Glucose CH3 (CH2 ) 1 4 COOH + 2 3 O2 Palmitic acid 6 CO2 + 6 H2 O 686 3.8 1 6 CO2 +1 6 H2 O 2,340 9.3 28-24 -Oxidation -Oxidation: A series of five enzyme-catalyzed reactions that cleaves carbon atoms two at a time from the carboxyl end of a fatty acid. • Reaction 1: The fatty acid is activated by conversion to an acyl CoA. Activation is equivalent to the hydrolysis of two high-energy phosphate anhydrides. O R-CH2 -CH2 -C-OH + ATP + CoA-SH A fatty acid O R-CH2 -CH2 -C-SCoA + AMP + 2 Pi An acyl CoA 28-25 -Oxidation • Reaction 2: Oxidation by FAD of the , carbon-carbon single bond to a carbon-carbon double bond. O R-CH2 -CH2 -C-SCoA A n acyl-CoA + FAD acyl-CoA dehydrogen ase O H C-SCoA + FADH2 C C R H A trans enoyl-CoA 28-26 -Oxidation • Reaction 3: Hydration of the C=C double bond to give a 2° alcohol. O enoyl-CoA H C-SCo A hydratas e + H2 O C C R H A trans enoyl-CoA OH R C H O CH2 -C- SCoA An L- -hydroxyacyl-CoA • Reaction 4: Oxidation of the 2 alcohol to a ketone. OH C H O CH2 -C-SCoA R -Hyd roxyacyl-CoA + NAD+ -h yd roxyacyl-CoA dehydrogenas e O O R-C-CH2 -C-SCoA + NADH + H+ -Ketoacyl-CoA 28-27 -Oxidation • Reaction 5: Cleavage of the carbon chain by a molecule of CoA-SH. O O th iolas e + R-C-CH2 -C-SCoA CoA-SH -Ketoacyl-CoA Coenzyme A O O R-C-SCoA + CH3 C-SCoA An acyl-CoA Acetyl-CoA 28-28 -Oxidation • This cycle of reactions is then repeated on the shortened fatty acyl chain and continues until the entire fatty acid chain is degraded to acetyl CoA. O CH3 ( CH2 ) 1 6 C-SCoA + Octadecanoyl-CoA (Stearyl-CoA) 8 CoA-SH + 8 NAD 8 FAD eigh t cycles of -oxidation O 9 CH3 C-SCoA + A cetyl-CoA 8 NADH 8 FADH2 • -Oxidation of unsaturated fatty acids proceeds in the same way, with an extra step that isomerizes the cis double bond to a trans double bond. 28-29 Energy Yield on -Oxidation • Yield of ATP per mole of stearic acid (C18). Step Chemical Step Happ ens ATP 1 Activation (stearic acid -> stearyl CoA) Once -2 2 Oxidation (acyl CoA —> trans-enoyl CoA) produces FA D H 2 8 times 16 4 Oxidation (hydroxy8 times acyl CoA to ketoacyl CoA ) produ ces N A D H +H + 24 Oxidation of acetyl CoA 9 times by the common metabolic path w ay, etc. TOTAL 108 146 28-30 Ketone Bodies • Ketone bodies: Acetone, -hydroxybutyrate, and acetoacetate; • Are formed principally in liver mitochondria. • Can be used as a fuel in most tissues and organs. • Formation occurs when the amount of acetyl CoA produced is excessive compared to the amount of oxaloacetate available to react with it and take it into the TCA; for example: • Dietary intake is high in lipids and low in carbohydrates. • Diabetes is not suitably controlled. • Starvation. 28-31 Ketone Bodies O 2 CH3 C-SCoA Acetyl-CoA HS-CoA O O CH3 CCH2 C-SCoA Acetoacetyl-CoA O NADH OH CH3 -C-CH2 -COOCH3 -CH-CH2 -COOA cetoacetate NAD+ + H+ -Hyd roxybutyrate CO2 O CH3 -C-CH3 Acetone 28-32 Protein Catabolism • Figure 28.7 Overview of pathways in protein catabolism. 28-33 Nitrogen of Amino Acids -NH2 groups move freely by transamination • Pyridoxal phosphate forms an imine (a C=N group) with the -amino group of an amino acid. • Rearrangement of the imine gives an isomeric imine. • Hydrolysis of the isomeric imine gives an -ketoacid and pyridoxamine. Pyridoxamine then transfers the -NH2 group to another -ketoacid. R- CH-COO RCH-COO N H2 - H2 O N + CH O E-Py r P CH An imine E-Py r P RC-COO R- C-COO + H2 O O N + CH2 N H2 E-Py r P CH2 An is omeric E-Py r P imine 28-34 Nitrogen of Amino Acids Nitrogens to be excreted are collected in glutamate, which is oxidized to -ketoglutarate and NH4+. • The conversion of glutamate to -ketoglutarate is an example of oxidative deamination. - COO + + NAD CH-NH3 + H2 O CH2 CH2 COOGlu tamate - COO NADH C=O CH2 + NH4 + CH2 COO-Ketoglutarate • NH4+ then enters the urea cycle. 28-35 Urea Cycle—An Overview Urea cycle: A cyclic pathway that produces urea from CO2 and NH4+. + CO2 + NH4 2 ATP 2 ADP + 2 H2 O + O - H3 N-CHCH2 COO Aspartate 2- H2 N-C-OPO3 Carbamoyl p hosphate O H 2 N-C-NH2 Urea COO- COO- H Urea cycle C C - OOC H Fumarate 28-36 Urea Cycle O N H3 + N H2 C O NH ( CH2 ) 3 ( CH 2 ) 3 H2 N -C- OPO 3 2 - CH- NH3 + COOOrnithine CH- NH3 + COOCitrulline COO + H3 N -CHCH2 COO As partate N H2 COOC N -CHCH 2 COO NH ( CH2 ) 3 CH- NH3 + COOArgininosuccinate (next screen) 28-37 Urea Cycle O H2 N -C- NH2 Urea N H3 + ( CH2 ) 3 CH- NH3 + COOOrnithine N H2 C N H2 + NH N H2 COOC N -CHCH2 COO NH ( CH2 ) 3 CH- NH3 + COOArginine ( CH2 ) 3 COO- H - C C OOC H Fumarate CH- NH3 + COOArgininosuccinate 28-38 Amino Acid Catabolism The breakdown of amino acid carbon skeletons follows two pathways. • Glucogenic amino acids: Those whose carbon skeletons are degraded to pyruvate or oxaloacetate, both of which may then be converted to glucose by gluconeogenesis. • Ketogenic amino acids: Those whose carbon skeletons are degraded to acetyl CoA or acetoacetyl CoA, both of which may then be converted to ketone bodies. 28-39 Amino Acid Catabolism Figure 28.9 Catabolism of the carbon skeletons of amino acids. 28-40 Amino Acid Catabolism Glucogenic Aspartate Asparagine Alanine Glycine Serine Threonine Cysteine Glutamate Glutamine Arginine Proline Histidine Valine Methionine Ketogenic Leucine Lys ine Glucogenic and Ketogenic Is oleucine Phenylalanine Tryptophan Tyrosine 28-41 Heme Catabolism When red blood cells are destroyed: • Globin is hydrolyzed to amino acids to be reused. • Iron is preserved in ferritin, an iron-carrying protein, and reused. • Heme is converted to bilirubin. • Bilirubin enters the liver via the bloodstream and is then transferred to the gallbladder where it is stored in the bile and finally excreted in the feces. 28-42 Chapter 28 Catabolic Pathways + CO2 + NH4 2 ATP 2 ADP + 2 H2 O + O 2- End Chapter 28 - H3 N-CHCH2 COO Aspartate H2 N-C-OPO3 Carbamoyl p hosphate O H 2 N-C-NH2 Urea COO- COO- H Urea cycle C C - OOC H Fumarate 28-43