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

1
Chapter 20Specific Catabolic PathwaysCarbohydra
te, Lipid, and ProteinMetabolism
2
What is the General Outline of Catabolic Pathway?

• Carbohydrates are broken down by enzymes and
  stomach acid to produce monosaccharides
• Lipids are hydrolyzed by lipase to glycerol and
  fatty acids or smaller units
• Proteins are hydrolyzed by HCl and digestive
  enzyme in the stomach and intestines to produce
  their constituent amino acids

3
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.

4
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.

5
Glycolysis

• Reaction 1 Phosphorylation of ?-D-glucose.

6
Glycolysis

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

7
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.

8
Glycolysis

• Reaction 3 Phosphorylation of fructose
  6-phosphate.

9
Glycolysis

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

10
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.

11
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.

12
Glycolysis

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

13
Glycolysis

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

14
Glycolysis

• Reaction 10 Phosphate transfer to ADP.

15
Glycolysis

• Summing these 10 reactions gives the net
  equation for glycolysis

16
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.

17
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.

18
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.

19
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.

20
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.

21
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.

22
Pentose Phosphate Pathway

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

23
Energy Yield in Glycolysis
24
Catabolism of Glycerol

• Glycerol enters glycolysis via dihydroxyacetone
  phosphate.

25
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.

26
?-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.

27
?-Oxidation

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

28
?-Oxidation

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

29
?-Oxidation

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

30
?-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.

31
Energy Yield on ?-Oxidation

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

32
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.

33
Ketone Bodies
34
Protein Catabolism

• Figure 20.7 Overview of pathways in protein
  catabolism.

35
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.

36
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.

37
Urea CycleAn Overview

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

38
Urea Cycle
39
Urea Cycle
40
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.

41
Amino Acid Catabolism

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

42
Amino Acid Catabolism
43
Hereditary Defects in Amino acid Catabolism PKU

• Occurs in the absence of the enzyme phenylalanine
  hydroxylase
• If the enzyme is defective, phenylalanine is
  convert to phenylpyruvate (?-ketoacid) instead of
  tyrosine
• Inhibits the conversion of pyruvate to acetyl
  CoA, depriving the cells of energy via the common
  catabolic pathway
• Results in mental retardation or PKU
  (Phenylketonuria)
• Prevention restricting the intake of
  phenylalanine in diet and artificial sweetener
  aspartate

44
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.

45
Heme Catabolism

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

The color change observed in bruises Black and
blue are due to the congealed blood, green to the
biliverdin and yellow to the bilirubin
46
Heme Catabolism

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