Catabolic-Pathways

Page 1:

• Specific catabolic pathways: Carbohydrate, Lipid, and Protein Metabolism

Page 2:

• Convergence of pathways

  • Specific pathways of carbohydrate, fat, and protein catabolism converge into a common pathway

Page 3:

• Glycolysis

  • A series of 10 enzyme-catalyzed reactions

  • Glucose is oxidized to two molecules of pyruvate

  • Net conversion of 2ADP to 2ATP

Page 4:

• Glycolysis Reaction 1

  • Phosphorylation of α-D-glucose

  • Catalyzed by hexokinase

  • α-D-Glucose is converted to α-D-Glucose 6-phosphate

Page 5:

• Glycolysis Reaction 2

  • Isomerization of glucose 6-phosphate to fructose 6-phosphate

  • Catalyzed by phosphohexose isomerase

  • α-D-Glucose 6-phosphate is converted to α-D-Fructose 6-phosphate

Page 6:

• Glycolysis Isomerization

  • Isomerization of glucose 6-phosphate to fructose 6-phosphate

  • Open-chain forms of each monosaccharide

  • One keto-enol tautomerism followed by another

Page 7:

• Glycolysis Reaction 3

  • Phosphorylation of fructose 6-phosphate

  • Catalyzed by phosphofructokinase

  • α-D-Fructose 6-phosphate is converted to α-D-Fructose 1,6-bisphosphate

Page 8:

• Glycolysis Reaction 4

  • Cleavage of fructose 1,6-bisphosphate to two triose phosphates

  • Catalyzed by aldolase

  • Fructose 1,6-bisphosphate is converted to D-Glyceraldehyde 3-phosphate and Dihydroxyacetone phosphate

Page 9:

• Glycolysis Reaction 5

  • Isomerization of triose phosphates

  • Catalyzed by phosphotriose isomerase

  • Only the D enantiomer of glyceraldehyde 3-phosphate is formed

Page 10:

• Glycolysis Reaction 6

  • Oxidation of the -CHO group of D-glyceraldehyde 3-phosphate

  • Catalyzed by glyceraldehyde 3-phosphate dehydrogenase

  • D-Glyceraldehyde 3-phosphate is converted to 1,3-Bisphosphoglycerate

Page 11:

• Glycolysis Reaction 7

  • Transfer of a phosphate group from 1,3-bisphosphoglycerate to ADP

  • Catalyzed by phosphoglycerate kinase

  • 1,3-Bisphosphoglycerate is converted to 3-Phosphoglycerate

Page 12:

• Glycolysis Reaction 8

  • Isomerization of 3-phosphoglycerate to 2-phosphoglycerate

• Glycolysis Reaction 9

  • Dehydration of 2-phosphoglycerate

• Glycolysis Reaction 10

  • Phosphate transfer to ADP

Page 13:

• Glycolysis Reaction 10 (continued)

  • Phosphate transfer to ADP

  • Catalyzed by pyruvate kinase

  • Phosphoenolpyruvate is converted to Pyruvate

Page 14:

• Glycolysis Net Equation

  • Net equation for glycolysis

  • Glucose is converted to Pyruvate

  • NADH, ATP, H2O, and H+ are produced

Page 15:

• Reactions of Pyruvate

  • Pyruvate is metabolized in three ways depending on conditions

  • Ethanol, Lactate, or Acetyl CoA and Citric acid cycle

Page 16:

• Reactions of Pyruvate (continued)

  • Glycolysis needs a continuing supply of NAD+

  • If no oxygen is present, another way must be found to reoxidize NADH to NAD+

Page 17:

• Pyruvate to Lactate

  • In vertebrates under anaerobic conditions, pyruvate is reduced to lactate

  • Lactate dehydrogenase (LDH) catalyzes the reaction

Page 18:

• Pyruvate to Lactate (continued)

  • Reduction to lactate allows glycolysis to continue

  • Increases the concentration of lactate and H+ in muscle tissue

  • Blood lactate reaches a certain level, muscle tissue becomes exhausted

Page 19: Pyruvate to Ethanol

• Yeasts and several other organisms regenerate NAD+ by this two-step pathway:

  • Decarboxylation of pyruvate to acetaldehyde.

  • Acetaldehyde is then reduced to ethanol.

• NADH is the reducing agent.

• Acetaldehyde is oxidized and is the reducing agent in this redox reaction.

• Pyruvate is converted to acetaldehyde by pyruvate decarboxylase.

• Acetaldehyde is converted to ethanol by alcohol dehydrogenase.

Page 20: 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.

Page 21: Pentose Phosphate Pathway

• The pentose phosphate pathway, also called a shunt.

• Figure 28.5 shows a simplified schematic representation of the pathway.

Page 22: Energy Yield in Glycolysis

• Glycolysis reactions and their energy yield:

  • Activation (glucose -> fructose 1,6-bisphosphate): ATP produced -2

  • Phosphorylation (glyceraldehyde 3-phosphate -> 1,3-bisphosphoglycerate): ATP produced 4

  • Phosphate transfer to ADP from 1,3-bisphosphoglycerate and phosphoenolpyruvate: ATP produced 4

  • Oxidative decarboxylation (pyruvate -> acetyl CoA): ATP produced 6

  • Oxidation to two acetyl CoA in the citric acid cycle: ATP produced 24

• Total ATP produced in glycolysis: 36

Page 23: Catabolism of Glycerol

• Glycerol enters glycolysis via dihydroxyacetone phosphate.

• Glycerol is converted to glycerol 1-phosphate.

• Glycerol 1-phosphate is converted to dihydroxyacetone phosphate.

Page 24: Fatty Acids and Energy

• Fatty acids in triglycerides are the principal storage form of energy for most organisms.

• Hydrocarbon chains in fatty acids 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.

• Palmitic acid is an example of a fatty acid.

Page 25: β-Oxidation

• β-Oxidation is 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.

• Reaction 2: Oxidation by FAD of the α,β carbon-carbon single bond to a carbon-carbon double bond.

• Reaction 3: Hydration of the C=C double bond to give a 2° alcohol.

• Reaction 4: Oxidation of the 2° alcohol to a ketone.

• Reaction 5: Cleavage of the carbon chain by a molecule of CoA-SH.

Page 26: β-Oxidation

• Reaction 2: Oxidation by FAD of the α,β carbon-carbon single bond to a carbon-carbon double bond.

• Reaction 3: Hydration of the C=C double bond to give a 2° alcohol.

Page 27: β-Oxidation

• Reaction 3: Hydration of the C=C double bond to give a 2° alcohol.

• Reaction 4: Oxidation of the 2° alcohol to a ketone.

Page 28: β-Oxidation

• Reaction 5: Cleavage of the carbon chain by a molecule of CoA-SH.

Page 29: β-Oxidation

• The cycle of reactions in β-oxidation is repeated on the shortened fatty acyl chain until the entire fatty acid chain is degraded to acetyl CoA.

• β-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.

Page 30: Energy Yield on β-Oxidation

• Yield of ATP per mole of stearic acid (C18):

  • Activation: ATP produced 8 times

  • Oxidation: FADH2 produced 8 times

  • Oxidation: NADH + H+ produced 9 times

  • Oxidation of acetyl CoA by the common metabolic pathway, etc.: ATP produced 146

Page 31: Ketone Bodies

• Ketone bodies (acetone, β-hydroxybutyrate, and acetoacetate) are formed principally in liver mitochondria.

• Ketone bodies can be used as a fuel in most tissues and organs.

• Formation of ketone bodies 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.

• Factors that can lead to the formation of ketone bodies include high lipid intake, low carbohydrate intake, uncontrolled diabetes, and starvation.

Page 32: Ketone Bodies

• The formation of ketone bodies involves the conversion of acetyl CoA to acetoacetyl-CoA, which is then converted to acetoacetate and β-hydroxybutyrate.

• Acetone is a byproduct of the breakdown of acetoacetate.

Page 33: Protein Catabolism

• Figure 28.7 provides an overview of pathways in protein catabolism.

Page 34: 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.

Page 35: Nitrogen of Amino Acids Nitrogens to be excreted are collected in glutamate

• Glutamate is oxidized to -ketoglutarate and NH4+.

• The conversion of glutamate to -ketoglutarate is an example of oxidative deamination.

• NH4+ then enters the urea cycle.

Page 36: Urea Cycle—An Overview

• Urea cycle: A cyclic pathway that produces urea from CO2 and NH4+.

Page 37: Urea Cycle

• Ornithine

• Aspartate

• Citrulline

• Argininosuccinate

Page 38: Urea Cycle

• Ornithine

• Arginine

• Urea

• Fumarate

Page 39: Amino Acid Catabolism

• 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.

Page 40: Amino Acid Catabolism Figure 28.9 Catabolism of the carbon skeletons of amino acids.

Page 41: Amino Acid Catabolism

• Glucogenic: Aspartate, Asparagine, Alanine, Glycine, Serine, Threonine, Cysteine, Glutamate, Glutamine, Arginine, Proline, Histidine, Valine, Methionine

• Ketogenic: Leucine, Lysine

• Glucogenic and Ketogenic: Isoleucine, Phenylalanine, Tryptophan, Tyrosine

Page 42: Heme Catabolism

• 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