Chapter 27Chapter 27

Specific Catabolic Specific Catabolic Pathways:Pathways:Carbohydrate, Lipid & Carbohydrate, Lipid & Protein MetabolismProtein Metabolism

1.

2. 3.

GlycolysisGlycolysis: Follow Along: : Follow Along: Figure 27.3Figure 27.3

GlycolysisGlycolysis• 10 enzyme-catalyzed reactions by which glucose is oxidized to two molecules of pyruvate.

• During glycolysis, there is net conversion of 2ADP to 2ATP.

C6H12O6Glucose

glycolysis2CH3CCOO-

Pyruvate

+ 2H+O

C6H12O6 + 2ADP + 2Pi 2CH3CCOO- + 2ATP

O

Glucose Pyruvate

HO

OHOH

HOCH2OH

O

O-

-O-P-O-P-O-AMP

O-

O O

Mg2+

OHOH

HOHO

CH2OPO32-

O-O-P-O-AMP

O

O-

ATP

ADP

-D-Glucose

+

+hexokinase

-D-Glucose 6-phosphate

NOTE: ATP = Energy molecule of choice

Glycolysis - Rxn 1Glycolysis - Rxn 1• reaction 1reaction 1:: phosphorylation of -D-glucose.

HO

OHOH

HOCH2OH

O

O-

-O-P-O-P-O-AMP

O-

O O

Mg2+

OHOH

HOHO

CH2OPO32-

O-O-P-O-AMP

O

O-

ATP

ADP

-D-Glucose

+

+hexokinase

-D-Glucose 6-phosphate

Glycolysis - Rxn 2Glycolysis - Rxn 2• reaction 2:reaction 2: isomerization of glucose 6-phosphate to fructose 6-phosphate.

O

OHOH

HOHO

CH2OPO32-

HO

CH2OPO32-

CH2OHO

OH

HH

HO

H

2

1

-D-Glucose 6-phosphate -D-Fructose 6-phosphate

phosphogluco- isomerase

6

12

6

Glycolysis - Rxn 2Glycolysis - Rxn 2• This isomerization is most easily seen by considering the open-chain forms of each monosaccharide; it is one keto-enol tautomerism followed by another.

CHO

CH2OPO32-

OHHHHOOHHOHH

C

CH2OPO32-

OHHHOOHHOHH

CH OHC

CH2OPO32-

OHHOOHHOHH

CH2OH

Fructose 6-phosphateGlucose 6-phosphate (An enediol)

2

1 1

2

Glycolysis - Rxn 3Glycolysis - Rxn 3• reaction 3:reaction 3: phosphorylation of fructose 6-phosphate.

1

HO

CH2OPO32-

CH2OHO

OH

HH

HO

-D-Fructose 6-phosphate

6

H

+ATP

phospho-fructokinase

Mg2+

1

HO

CH2OPO32-

CH2OPO32-O

OHH

HHO

-D-Fructose 1,6-bisphosphate

6

H

+ ADP

ATP ADP

Glycolysis - Rxn 4Glycolysis - Rxn 4• reaction 4:reaction 4: cleavage of fructose 1,6-bisphosphate to two triose phosphates.

H

C=O

CH2OPO32-

HOH

CH2OPO32-

OHH

HO

CH2OPO32-

C

CHO

H OH

C=O

CH2OPO32-

CH2OHaldolase

Fructose 1,6-bisphosphate

D-Glyceraldehyde3-phosphate

Dihydroxyacetonephosphate

Glycolysis - Rxn 5Glycolysis - Rxn 5• reaction 5: reaction 5: isomerization of triose phosphates.• Catalyzed by phosphotriose isomerase.• Reaction involves two successive keto-enol tautomerizations.

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

C=O

CH2OPO32-

CH2OH

CH2OPO32-

CCHO

H OH

D-Glyceraldehyde3-phosphate

Dihydroxyacetonephosphate

C-OHCHOH

CH2OPO32-

An enediolintermediate

Glycolysis - Rxn 6Glycolysis - Rxn 6• Reaction 6Reaction 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.

CH2OPO32-

CCHO

H OH NAD+

CCH2OPO3

2-

C-OPO32-

OHH

O

NADH

1,3-Bisphospho-glycerate

D-Glyceraldehyde3-phosphate

+ + Pi

+

glyceraldehyde3-phosphate

dehydrogenase

Glycolysis - Rxn 7Glycolysis - Rxn 7• Reaction 7: Reaction 7: transfer of a phosphate group from 1,3-bisphosphoglycerate to ADP.

CCH2OPO3

2-

C-OPO32-

OHH

O

-O-P-O-AMPO

O-

CCH2OPO3

2-

COO-

OHH

ADP

Mg2+

O

O-

-O-P-O-P-O-AMPO

O-

ATP

+

1,3-Bisphospho-glycerate

+

3-Phosphoglycerate

phospho-glycerate kinase

CCH2OPO3

2-

C-OPO32-

OHH

O

-O-P-O-AMPO

O-

CCH2OPO3

2-

COO-

OHH

ADP

Mg2+

O

O-

-O-P-O-P-O-AMPO

O-

ATP

+

1,3-Bisphospho-glycerate

+

3-Phosphoglycerate

phospho-glycerate kinase

Glycolysis - Rxn 8 & Glycolysis - Rxn 8 & 99• Reaction 8: Reaction 8: isomerization of 3-

phosphoglycerate to 2-phosphoglycerate.

• Reaction 9: Reaction 9: dehydration of 2-phosphoglycerate.

C

CH2OPO32-

COO-

OHH CCH2OH

COO-

OPO32-H

3-Phosphoglycerate 2-Phosphoglycerate

phosphoglycerate mutase

CCH2OH

COO-

OPO32-H

Mg2+ CCH2

COO-

OPO32- H2O

2-Phosphoglycerate Phosphoenolpyruvate

+enolase

Glycolysis - Rxn 10Glycolysis - Rxn 10• Reaction 10Reaction 10: phosphate transfer to ADP

CCH2

COO-

OPO32- -O-P-O-AMP

O-

O

C=OCH3

COO-

ADP

Mg2+

-O-P-O-P-O-AMPO-O-

O O

ATP

Phosphoenol- pyruvate

+

+

Pyruvate

pyruvate kinase

CCH2

COO-

OPO32- -O-P-O-AMP

O-

O

C=OCH3

COO-

ADP

Mg2+

-O-P-O-P-O-AMPO-O-

O O

ATP

Phosphoenol- pyruvate

+

+

Pyruvate

pyruvate kinase

GlycolysisGlycolysis: SUMMARY: : SUMMARY:

Figure 27.3

Note: Glycer-3 phosphate X 22 ATP produced

2 ATP produced

1 ATP used 1 ATP used

Glycolysis: SummaryGlycolysis: Summary• The net equation for glycolysis:

C6H12O6 + 2NAD+ + 2HPO42- + 2ADP

Glucose

glycolysis

2CH3CCOO-O

Pyruvate+ 2NADH + 2ATP + 2H2O + 2H+

Confirming your Confirming your knowledgeknowledge

• Of the 36 molecules of ATP produced by the complete metabolism of glucose, how many are produced in glycolysis alone? ____

• What is the net total ATP production?

Total: 36 ATP

___ ATP

Reactions of Pyruvate: Reactions of Pyruvate: Fig 27.4Fig 27.4• Pyruvate metabolized three ways:• depends on organism & presence/absence of O2

CH3CCOO-O

CH3CH2OH

CH3CHCOO-OH

+ CO2

Pyruvate

Ethanol

Lactate

anaerobic conditions

aerobic conditionsplants and animals

contracting muscle

anaerobic conditionsfermentation in yeast

Acetyl CoA Citric acid cycle

10

12

11

13

NOTE:Anaerobic = w/o OxygenAerobic = w/ Oxygen

Reactions of PyruvateReactions 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 it.

Pyruvate to LactatePyruvate to Lactate• Under anaerobic (NO Oxygen) conditions, the most important pathway for the regeneration of NAD+ is reduction of pyruvate to lactate. Pyruvate, the oxidizing agent, is reduced to lactate.CH3CCOO- + NADH + H+

O

Pyruvate

CH3CHCOO- + NAD+OH

Lactate

lactatedehydrogenase

Pyruvate to LactatePyruvate 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, esp. b/c H+ ions.

C6H12O6

Glucose

2CH3CHCOO- + 2H+OH

Lactate

lactatefermentation

((ACID!))

Pyruvate to EthanolPyruvate to Ethanol• Yeasts and several other organisms regenerate NAD+ by this two-step pathway:• decarboxylation of pyruvate to acetaldehyde.

• Acetaldehyde is reduced to ethanol.

Pyruvate

CH3CH + CO2

O

Acetaldehyde

pyruvatedecarboxylase

CH3CCOO- + H+O

CH3CH + NADH + H+O

Acetaldehyde

alcoholdehydrogenase

CH3CH2OH + NAD+

Ethanol

Pyruvate to Acetyl-Pyruvate to Acetyl-CoACoA

• 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.

Pyruvate

CH3CSCoA + CO2 + NADHO

Acetyl-CoA

oxidativedecarboxylation

CH3CCOO- + NAD+ + CoASHO

Confirming your Confirming your knowledgeknowledge

• The end product of glycolysis (pyruvate) cannot enter as such into the citric acid cycle.

• What is the name of the process that converts this C3 compound to a C2 compound?

Catabolism of GlycerolCatabolism of Glycerol• Glycerol enters glycolysis via dihydroxyacetone

phosphate.

CH

CH2OH

CH2OHOH

ATP ADPCH

CH2OPO32-

CH2OHOH

NAD+ NADHC=OCH2OH

CH2OPO32-

Glycerol Glycerol1-phosphate

Dihydroxyacetonephosphate

7.3 kcal/mole

3.4 kcal/mole.

Challenge QuestionChallenge Question• Which yields more Energy upon hydrolysis:

ATP or glycerol 1- phosphate and Why?

CH

CH2OH

CH2OHOH

ATP ADPCH

CH2OPO32-

CH2OHOH

NAD+ NADHC=OCH2OH

CH2OPO32-

Glycerol Glycerol1-phosphate

Dihydroxyacetonephosphate

SummarySummary• Glycolysis yields 2 net ATP• ATP is the molecule of choice for cell(s) Energy

• ATP is a High E yielding molecule (7.3 kcal/mole)

• Pyruvate is the END product of Glycolysis

» under aerobic conditions Acetyl CoA further ATP!!!

» under anaerobic conditions Lactate (muscle fatigue)

Pyruvate

CH3CSCoA + CO2 + NADHO

Acetyl-CoA

oxidativedecarboxylation

CH3CCOO- + NAD+ + CoASHO