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Principles and Applications ofInorganic, Organic, and

BiologicalChemistryDenniston, Topping, and Caret

4th edChapter 21

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Power Point to Accompany

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IntroductionMajor pathways of carbohydrate metabolism.

Fig 8.1 3rd ed

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21.1 ATP: Cellular Energy CurrencyComplete combustion of a mole of glucose

yields 686 kcal. Adenosine triphosphate (ATP) serves as a “go-between” molecule that couples exergonic catabolism reactions to endergonic anabolic reactions.

ATP “captures “ energy as phosphoanhydride bonds.

OP

O

O

O OP

O

O OCH2

HOH

H

OH

HH

N N

N N

NH2

OP

O

O----

Phosphoester bond

Phosphoanhydride bondsHydrolysis of

the anhydride bonds provides energy for anabolism.

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ATP ExampleATP + H2O ADP + Pi + 7 kcal/mol

3.0 kcal/mol + glucose + Pi

glucose-6-phosphate + H2O

Net ___________________________________

Glucose + ATP

glucose-6-phosphate + ADP + 4 kcal/mol

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21.2 Catabolism

Insert Fig 21.4DTC

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Catabolism-cont.Stage 1: Hydrolysis to Small Subunits Food molecules are degraded:Polysaccharides

Begins in the mouth with amylase action on starch. Continues in small intestine (SI) to form monosaccharides.

ProteinsBegins in the stomach. In SI to amino

acids.Fats

Begins in SI. To fatty acids and glycerol.

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Catabolism-cont.Stage 2: Conversion of monomers to a form

that can be completely oxidized.

Sugars: glycolysis and TCA cycle

Fatty acids: enter TCA cycle as acetyl CoA

Stage 3: Complete Oxidation/ATP produced.

Acetyl CoA enters the TCA cycle and electrons and hydrogen atoms are harvested as CO2 is produced.

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21.3 Glycolysis (Embden-Meyerhof Pathway)

The anerobic oxidation of glucose (G) to give two molecules of pyruvate.

G + 2 ADP + 2 Pi + 2 NAD+ 2 pyruvate +2 ATP + 2 NADH + 2 H+ + 2 H2O

CH3CO

C OO

Products:Substrate-level phosphorylation gives 4 ATP

A phosphoryl group is transferred to ADP! from 1,3-bisphosphoglycerate and phosphoenolpyruvate.

NADH carries hydride anions with two electrons.

Pyruvate: fate depends on cellular conditions.

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Glycolysis: Step 1, 2

hexokinase

glucose

+ ATP

OCH2

HH

OHH

OH

OH

HOH

HOH

O

CH2

H

OH

H

H

OHOH

CH2OHOPO3

2-

fructose-6-phosphate

+ ADP

glucose-6-phosphate

OCH2

HH

OHH

OH

OH

HOH

HOPO3

2-

phosphoglucose

isomerase

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Glycolysis: Step 3 (Committed Step)

+ ATP

O

CH2

H

OH

H

H

OHOH

CH2OOPO3

2-

PO32-

fructose-1,6-bisphosphate

+ ADP

phosphofructokinaseO

CH2

H

OH

H

H

OHOH

CH2OHOPO3

2-

Two molecules of ATP have now been used.

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Glycolysis: Step 4, 5

O

CH2

H

OH

H

H

OHOH

CH2OOPO3

2-

PO32-

dihydroxyacetone phosphate

D-glyceraldehyde-3-phosphate

aldolase

CH2CCH2

OOOH

PO32-

CHCCH2

OOHO

HPO3

2-

+

triosephosphate isomeraseCH

CCH2

OOHO

HPO3

2-

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Glycolysis: Step 6

CH

C

CH2

O

OH

OPO32-

H

+ NAD+ + HPO42-

Glycerate-1,3-bisphosphate

C

C

CH2

O

OH

OPO32-

H

OPO32-

+ NADH + H+

glyceraldehyde 3-phosphatedehydrogenase

Phosphorylation and a two electron oxidation by NAD+ occur.

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Glycolysis: Step 7, 8

C

C

CH2

O

OH

OPO32-

H

OPO32-

+ ADP

C

C

CH2

O

OH

OPO32-

H

O

3-phosphoglycerate

+ ATPphospho-glyceratekinase

phosphoglyceratemutase

C

C

CH2

O

OPO32-

OH

H

O

2-phosphoglycerate

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Glycolysis: Step 9, 10

C

C

CH2

O

O

O

PO32-

Phosphoenolpyruvate(PEP)

+ H2O

enolase

“High energy bond”C

C

CH2

O

OPO32-

OH

HO

CCCH3

O

OO

+ ATP

pyruvate

pyruvatekinase

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Regulation of Glycolysis

Enzyme Activator Inhibitor

Hexokinase

(Step 1)

Glucose-6-

Phosphate, ATP

PFK

(Step 3)

Fructose-2,6-bis

phosphate, AMP

Citrate, ATP

Pyruvate

kinase

(Step 10)

Fructose-1,6-bis

phosphate, AMP

Acetyl-CoA, ATP

All the above enzymes are allosteric.

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21.4 Fermentation

+ NADH + H+

lactatedehydrogenase

lactate+ NAD+

CCCH3

O

OO C

CCH3

O

OHOH

This reaction produces NAD+ which is needed for further anerobic glycolysis.

Glyceraldehyde 3-phosphate

--> glycerate-1,3-bisphosphate

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Fermentation, cont,

pyruvatedecarboxylase

ethanol +NAD+

NADH+ H+

CCH3

OH+CO2C

C

CH3

O

O

O

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21.5 Pentose Phosphate PathwayThe PP Pathway is an alternative to

glycolysis.In stage 1, the oxidative stage, NADPH for

biosynthesis is produced.In stage 2, three ribulose-5-phosphate result.In stage 3, ribose-5-phosphate and two

xylulose-5-phosphate are produced along with two fructose-6-P and glyceraldehyde-3-P.

The nonoxidative stages (2, 3) produce sugars with from 3 to 7 carbons. The ribose sugar is critical for nucleic acid synthesis.

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21.6 GluconeogenesisGluconeogenesis makes glucose from

noncarbohydrate (lactate, glycerol, and most AA) starting materials primarily in the liver.

The three nonreversable steps of glycolysis must be bypassed with new routes.

Pyruvate PEP

Fructose-1,6-bisP furctose-6-P

Glucose-6-P glucose

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Pyruvate to PEP

+ ATP

+ CO2 + H2O

pyruvatecarboxylase

CCCH3

O

OO

oxaloacetate

+ ADP

+ Pi + H+CCCH2

O

OO

C

O

O

CC

CH2

O

OO

PO

OO

Phosphoenol-pyruvate carboxykinase

GTP

CO2 + GDP +

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F-1,6-bP F-6-P and G-6-P Glucose

fructose-1,6-bisphosphatase

O

CH2

H

OH

H

H

OH

OH

CH2 OO PO3

2-

PO32-

O

CH2

H

OH

H

H

OHOH

CH2 OH

O PO32-

OCH2OPO3

2-

HH

OHH

OH

OH

HH

OH

+ H2O

glucose-6-phosphatase

OCH2OH

HH

OHH

OH

OH

HH

OH

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Gluconeogenesis SubstratesStep 3 glycolysis:

phosphofructokinase

Stimulated by: high AMP, ADP, Pi

Inhibited by: high ATP

Reverse gluconeogenesis:

fructose-1,6-bisphosphatase

Stimulated by: high ATP

In the Cori cycle, lactate from skeletal muscle is transferred to the liver where it is converted to pyruvate then glucose which can be returned to the muscle.

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21.7 GlycogenGlucose is the sole source of energy for

mammalian red blood cells and the major source for the brain.

It is supplied in the diet, via glycogenolysis, or by gluconeogenesis.

Glycogen (Ch 17) is a highly branched (14) and (16) polymer of glucose.

It exists as granules found in the cytoplasm of liver and muscle cells.

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GlycogenolysisGlycogen degradation) is controlled by

glucagon (pancreas) and epinephrine (adrenal gland).

The pancreas responds to low blood sugar and the adrenal gland to stress/threat.

Step 1: Glycogen phosphorylase catalyzes removal of an end glucose as glucose-1-P.

Step 2: Debranching enzyme catalyzes removal of the last glucose at an (16) branch as glucose.

Step 3: Phosphoglucomutase converts glucose-1-P to glucose-6-P.

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GlycogenesisInsulin (pancreas) stimulates synthesis of

glycogen.

glucose + ATP glucose-6-P + ADP + H+

Enzyme: glucokinase

glucose-6-P glucose-1-P

Enzyme: phosphoglucomutase

Now the glucose must be activated to add to the growing glycogen chain.

G-1-P + UTP UDP-glucose + PPi

(see next slide)

UDP-glucose adds to the growing glycogen.

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Glycogenesis-2

Pyrophosphate hydrolyzes

OCH2

OHOH

OH

OPO32-

OH

+ UTP

OCH2

OHOH

OH

O

OH

PO

OO P

O

OO uridine

+ PPi

UDP glucose-phosphorylase

H2O

2 Pi

UDPG

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Glycogenesis-3

Glycogen synthase

OCH2

OHOH

OH

O

OH

PO

OO P

O

OO U

+O

CH2

OHOH

OH

O

OH

Glucoseglycogen chain

glycogen chain

OCH2

OHOH

OH

O

OHO

CH2

OH

OH

O

OH

Glucose

+ UDP

A new-1,4 bondis formed

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Glycogenesis vs GlycogenolysisHigh blood sugar (hyperglycemia)

Insulin: stimulates glucose uptake

elevates glucokinase

activates glycogen synthetase

inhibits glycogen phosphorylase

Low blood sugar (hypoglycemia)

Glucagon: stimulates glycogen phosphorylase

Inhibits glycogen synthetase

Thus glycogen synthesis and degradation do not compete.

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The End

Carbohydrate Metabolism