Chapter 20 Specific Catabolic Pathways: Carbohydrate, Lipid, and Protein Metabolism

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Chapter 20Specific Catabolic PathwaysCarbohydra
te, Lipid, and ProteinMetabolism
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Convergence of Pathways

• Figure 20.2 Convergence of the specific pathways
  of carbohydrate, fat, and protein catabolism into
  the common pathway, which is made up of citric
  acid cycle and oxidative phosphorylation.

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Glycolysis

• Glycolysis A series of 10 enzyme-catalyzed
  reactions by which glucose is oxidized to two
  molecules of pyruvate.
• During glycolysis, there is net conversion of
  2ADP to 2ATP.

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Glycolysis

• Reaction 1 Phosphorylation of ?-D-glucose.

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Glycolysis

• Reaction 2 Isomerization of ?-D-glucose
  6-phosphate to ?-D-fructose 6-phosphate.

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Glycolysis

• This isomerization is most easily seen by
  considering the open-chain forms of each
  monosaccharide. It is one keto-enol tautomerism
  followed by another.

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Glycolysis

• Reaction 3 Phosphorylation of fructose
  6-phosphate.

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Glycolysis

• Reaction 4 Cleavage of fructose 1,6-bisphosphate
  to two triose phosphates.

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Glycolysis

• Reaction 5 Isomerization of triose phosphates.
• Catalyzed by phosphotriose isomerase. The
  mechanism involves two successive keto-enol
  tautomerizations.
• Only the D enantiomer of glyceraldehyde
  3-phosphate is formed.

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Glycolysis

• Reaction 6 Oxidation of the -CHO group of
  D-glyceraldehyde 3-phosphate.
• The product contains a phosphate ester and a
  high-energy mixed carboxylic-phosphoric
  anhydride.

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Glycolysis

• Reaction 7 Transfer of a phosphate group from
  1,3-bisphosphoglycerate to ADP.

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Glycolysis

• Reaction 8 Isomerization of 3-phosphoglycerate
  to 2-phosphoglycerate.
• Reaction 9 Dehydration of 2-phosphoglycerate.

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Glycolysis

• Reaction 10 Phosphate transfer to ADP.

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Glycolysis

• Summing these 10 reactions gives the net
  equation for glycolysis

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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.

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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.

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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 dehydrogenase (LDH) is a tetrameric
  isoenzyme consisting of H and M subunits H4
  predominates in heart muscle, M4 in skeletal
  muscle.

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Pyruvate to Lactate

• While reduction to lactate allows glycolysis to
  continue, it increases the concentration of
  lactate and also of H in muscle tissue.
• When blood lactate reaches about 0.4 mg/100 mL,
  muscle tissue becomes almost completely exhausted.

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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 reduced and
  is the oxidizing agent in this redox reaction.

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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.

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Pentose Phosphate Pathway

• Figure 20.5 Simplified schematic representation
  of the pentose phosphate pathway, also called a
  shunt.

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Energy Yield in Glycolysis
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Catabolism of Glycerol

• Glycerol enters glycolysis via dihydroxyacetone
  phosphate.

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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.

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?-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.

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?-Oxidation

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

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?-Oxidation

• Reaction 3 Hydration of the CC double bond to
  give a 2 alcohol.
• Reaction 4 Oxidation of the 2?alcohol to a
  ketone.

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?-Oxidation

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

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?-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.
• b-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.

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Energy Yield on ?-Oxidation

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

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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.

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Ketone Bodies
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Protein Catabolism

• Figure 20.7 Overview of pathways in protein
  catabolism.

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Nitrogen of Amino Acids

• -NH2 groups move freely by transamination
• Pyridoxal phosphate forms an imine (a CN 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
  a-ketoacid.

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Nitrogen of Amino Acids

• Nitrogens to be excreted are collected in
  glutamate, which is oxidized to a-ketoglutarate
  and NH4.
• The conversion of glutamate to ?-ketoglutarate is
  an example of oxidative deamination.
• NH4 then enters the urea cycle.

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Urea CycleAn Overview

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

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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.

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Amino Acid Catabolism

• Figure 20.9 Catabolism of the carbon skeletons
  of amino acids.

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Amino Acid Catabolism
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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.

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Heme Catabolism

• Figure 20.10 Heme degradation from heme to
  biliverdin to bilirubin.

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Heme Catabolism

• Figure 20.11 A summary of catabolism showing
  the role of the common metabolic pathway.