©1998 by Alberts, Bray, Johnson, Lewis, Raff, Roberts, Walter. http://www.essentialcellbiology.com Published by Garland Publishing, a member of the Taylor & Francis Group.

Outline of Sugar Types Found in Cells - Part 1

Monosaccharides usually have the general formula (CH2O) n , where n can be 3, 4, 5, 6, 7, or 8, and have two or more hydroxyl groups. They either contain an aldehyde group ( ) and are called aldoses or a ketone group ( ) and are called ketoses.

MONOSACCHARIDES

Note that each carbon atom has a number.

Many monosaccharides differ only in the spatial arrangement of atoms—that is, they are isomers. For example, glucose, galactose, and mannose have the same formula (C6H12O6) but differ in the arrangement of groups around one or two carbon atoms.

These small differences make only minor changes in the chemical properties of the sugars. But they are recognized by enzymes and other proteins and therefore can have important biological effects.

RING FORMATION ISOMERS

C

C

H

HHO

OH

CH OH

CH OH

CH

H

OH

C

H

H

HO

OH

CH OH

CH OH

CH

H

OH

CH OH

CH OH

CH OH

CH

H

OH

CH OH

CH

H

OH

3-carbon (TRIOSES) 5-carbon (PENTOSES) 6-carbon (HEXOSES)

ALD

OS

ES

KE

TO

SE

S

C

OH

C

OHC

OH

glyceraldehyde ribose glucose

fructose

H

H

OH

CH OH

CH OH

CH

H

OH

ribulose

H

H

OH

CH

H

OH

dihydroxyacetone

O

C

C

O

C

C

O

C

C

CH

CH2OH

CH2OH

OH

CH OH

CHO H

CH

H

H

HH

H

H H

HH

H

HO

OH

OH

OH

OH

OH

OHOH

CO

O

CH2OH

CH

CH2OH

OH

CH OH

CH OH

1

2

3

4

4

4

5

5

6

3

3

2

2

1

CH2OH

HH

H

H

H

HOOH

OH

OH

O

1

5

1

2

3

4

5

6

glucose

CH2OH

H

H

H

H

H

HOOH

OH

OH

O

mannose

CH2OH

HH

H

H

H

HO

OH

OH

OHgalactose

O

O

CO

C OH

glucose

ribose

In aqueous solution, the aldehyde or ketone group of a sugarmolecule tends to react with a hydroxyl group of the samemolecule, thereby closing the molecule into a ring.

HC

O

©1998 by Alberts, Bray, Johnson, Lewis, Raff, Roberts, Walter. http://www.essentialcellbiology.com Published by Garland Publishing, a member of the Taylor & Francis Group.

Outline of Sugar Types Found in Cells - Part 2

CH2OH

HO

O

OH

OH

CH2OH

OH

CH2OH

NH

HOCH2

HO

CH2OH

HO

O

OH

OH

O H CH2OH

OH

HOCH2

HO

HO

+

O

CH2OH

O CH2OH

O

OH

O

HO

OH

HO

O OH

NH

OO

HO

CH3

O

In many cases a sugar sequence is nonrepetitive. Many different molecules are possible. Such complex oligosaccharides are usually linked to proteins or to lipids, as is this oligosaccharide, which is part of a cell-surface moleculethat defines a particular blood group.

COMPLEX OLIGOSACCHARIDES

OLIGOSACCHARIDES AND POLYSACCHARIDESLarge linear and branched molecules can be made from simple repeating units.Short chains are called oligosaccharides, while long chains are calledpolysaccharides. Glycogen, for example, is a polysaccharide made entirely ofglucose units joined together.

branch points glycogen

sucrose

a glucose b fructoseDISACCHARIDES The carbon that carries the aldehyde or the ketone can react with any hydroxyl group on a second sugar molecule to form a disaccharide. Three common disaccharides are

maltose (glucose + glucose) lactose (galactose + glucose) sucrose (glucose + fructose)

The reaction forming sucrose is shown here.

a AND b LINKS SUGAR DERIVATIVESThe hydroxyl group on the carbon that carries the aldehyde or ketone can rapidly change from one position to the other. These two positions are called a and b .

As soon as one sugar is linked to another, the a or b form is frozen.

The hydroxyl groups of a simple monosaccharide can be replaced by other groups. For example,

C O

CH3

C O

CH3

OHO

OH

O

b hydroxyl a hydroxyl

C

O

OH

OH

OH

HO

OH

CH2OH

CH2OHNH2

H

O

OH

OH

HO

O

OH

OH

HO

CH3

O

NH

C

Hglucosamine

N-acetylglucosamineglucuronic acid

O

H2O

O

O

O

P

ATP ADP

CH2OH

O

OH

OH

OHHO

glucose

CH2O

H+

O

OH

OH

OHHO

glucose 6-phosphate

+ + +

hexokinase

P

P

CH2O

O

OH

OH

OHHO

glucose 6-phosphate fructose 6-phosphate

(ring form) (ring form)

(open-chain form)

1

1

2

2

3

4

56

6

O H

C

CH OH

CHO H

CH OH

CH OH

CH2O

3

4

5

P

P

(open-chain form)

1

1

2

2

6

C

CHO H

CH OH

CH OH

CH2O

CH2OH

3

34 4

5

5

phosphoglucoseisomerase OH2C CH2OHO

HO

OH

OH

6

ATP+ ADP H++ +phosphofructokinaseP OH2C CH2OHO

HO

OH

OH

P POH2C CH2OO

HO

OH

OH

Glucose is phosphorylated by ATP to form a sugar phosphate. The negative charge of the phosphate prevents passage of the sugarphosphate through the plasma membrane, trapping glucose inside the cell.

Step 1

The six-carbon sugar is cleaved to produce two three-carbon molecules. Only the glyceraldehyde3-phosphate can proceed immediately through glycolysis.

Step 4

The other product of step 4, dihydroxyacetone phosphate, is isomerized to form glyceraldehyde 3-phosphate.

Step 5

A readily reversible rearrangement of the chemical structure (isomerization) moves the carbonyl oxygen from carbon 1 to carbon 2, forming a ketose from an aldose sugar. (See Panel 2–3, pp. 70–71.)

Step 2

The new hydroxyl group on carbon 1 is phosphorylated by ATP, in preparation for the formation of two three-carbon sugar phosphates. The entry of sugars into glycolysis is controlled at this step, through regulation of the enzyme phosphofructokinase.

Step 3

fructose 6-phosphate fructose 1,6-bisphosphate

+

(ring form)

OH

C

CH OH

aldolase

P

P

(open-chain form)

C

CHO H

CH OH

CH OH

CH2O

CH2O

O

P

C

CHO H

H

CH2O

PCH2O

O

P POH2C CH2OO

HO

OH

OH

fructose 1,6-bisphosphatedihydroxyacetone

phosphateglyceraldehyde

3-phosphate

O

P

C

CH2O

CH2OH triose phosphate isomerase

OH

C

CH OH

PCH2O

glyceraldehyde3-phosphate

dihydroxyacetonephosphate

O

For each step, the part of the molecule that undergoes a change is shadowed in blue,and the name of the enzyme that catalyzes the reaction is in a yellow box.

Panel 13–1 Details of the 10 steps of glycolysis

+ +ADP

enolase

phosphoglycerate mutase

+

O O–

C

CH OH

PCH2O

3-phosphoglycerate

O O–

C

CH O P

CH2OH

2-phosphoglycerate

O O–

C

CH O P

CH2OH

2-phosphoglycerate

O O–

C

C O P

CH2

H2O

phosphoenolpyruvate

O O–

C

C O P

CH2

phosphoenolpyruvate

O O–

C

C O

CH3

pyruvate

O O–

C

C O

CH3

O O–

C

C O

CH3

ATP+ ADP

phosphoglycerate kinaseO O

C

CH OH

P

P

CH2O

1,3-bisphosphoglycerate

+

O O–

C

CH OH

PCH2O

3-phosphoglycerate

The two molecules of glyceraldehyde 3-phosphate are oxidized. The energy-generation phase of glycolysis begins, as NADH and a new high-energy anhydride linkage to phosphate are formed (see Figure 13–5).

Step 6

H+

+ ++

glyceraldehyde 3-phosphatedehydrogenaseO H

C

CH OH

PCH2O

glyceraldehyde3-phosphate

O O

C

CH OH

P

P

CH2O

1,3-bisphosphoglycerate

NADH

NADH

H++

The transfer to ADP of the high-energy phosphate group that was generated in step 6 forms ATP.

Step 7

The remaining phosphate ester linkage in 3-phosphoglycerate, which has a relatively low free energy of hydrolysis, is moved from carbon 3 to carbon 2 to form 2-phosphoglycerate.

Step 8

The removal of water from 2-phosphoglycerate creates a high-energy enol phosphate linkage.

Step 9

The transfer to ADP of the high-energy phosphate group that was generated in step 9 forms ATP, completing glycolysis.

Step 10

NET RESULT OF GLYCOLYSIS

ATP

ATP

+pyruvate kinase

CH2OH

O

OH

OH

OHHO

glucosetwo molecules

of pyruvate

ATP

ATP

NADH ATP

ATP

ATP

In addition to the pyruvate, the net products aretwo molecules of ATP and two molecules of NADH.

1

2

3

PiNAD+

P

ATP ADP

CH2OH

O

OH

OH

OHHO

glucose

CH2O

H+

O

OH

OH

OHHO

glucose 6-phosphate

+ + +

hexokinase

P

P

CH2O

O

OH

OH

OHHO

glucose 6-phosphate fructose 6-phosphate

(ring form) (ring form)

(open-chain form)

1

1

2

2

3

4

56

6

O H

C

CH OH

CHO H

CH OH

CH OH

CH2O

3

4

5

P

P

(open-chain form)

1

1

2

2

6

C

CHO H

CH OH

CH OH

CH2O

CH2OH

3

34 4

5

5

phosphoglucoseisomerase OH2C CH2OHO

HO

OH

OH

6

ATP+ ADP H++ +phosphofructokinaseP OH2C CH2OHO

HO

OH

OH

P POH2C CH2OO

HO

OH

OH

Glucose is phosphorylated by ATP to form a sugar phosphate. The negative charge of the phosphate prevents passage of the sugarphosphate through the plasma membrane, trapping glucose inside the cell.

Step 1

The six-carbon sugar is cleaved to produce two three-carbon molecules. Only the glyceraldehyde3-phosphate can proceed immediately through glycolysis.

Step 4

The other product of step 4, dihydroxyacetone phosphate, is isomerized to form glyceraldehyde 3-phosphate.

Step 5

A readily reversible rearrangement of the chemical structure (isomerization) moves the carbonyl oxygen from carbon 1 to carbon 2, forming a ketose from an aldose sugar. (See Panel 2–3, pp. 70–71.)

Step 2

The new hydroxyl group on carbon 1 is phosphorylated by ATP, in preparation for the formation of two three-carbon sugar phosphates. The entry of sugars into glycolysis is controlled at this step, through regulation of the enzyme phosphofructokinase.

Step 3

fructose 6-phosphate fructose 1,6-bisphosphate

+

(ring form)

OH

C

CH OH

aldolase

P

P

(open-chain form)

C

CHO H

CH OH

CH OH

CH2O

CH2O

O

P

C

CHO H

H

CH2O

PCH2O

O

P POH2C CH2OO

HO

OH

OH

fructose 1,6-bisphosphatedihydroxyacetone

phosphateglyceraldehyde

3-phosphate

O

P

C

CH2O

CH2OH triose phosphate isomerase

OH

C

CH OH

PCH2O

glyceraldehyde3-phosphate

dihydroxyacetonephosphate

O

For each step, the part of the molecule that undergoes a change is shadowed in blue,and the name of the enzyme that catalyzes the reaction is in a yellow box.

Panel 13–1 Details of the 10 steps of glycolysis

+ +ADP

enolase

phosphoglycerate mutase

+

O O–

C

CH OH

PCH2O

3-phosphoglycerate

O O–

C

CH O P

CH2OH

2-phosphoglycerate

O O–

C

CH O P

CH2OH

2-phosphoglycerate

O O–

C

C O P

CH2

H2O

phosphoenolpyruvate

O O–

C

C O P

CH2

phosphoenolpyruvate

O O–

C

C O

CH3

pyruvate

O O–

C

C O

CH3

O O–

C

C O

CH3

ATP+ ADP

phosphoglycerate kinaseO O

C

CH OH

P

P

CH2O

1,3-bisphosphoglycerate

+

O O–

C

CH OH

PCH2O

3-phosphoglycerate

The two molecules of glyceraldehyde 3-phosphate are oxidized. The energy-generation phase of glycolysis begins, as NADH and a new high-energy anhydride linkage to phosphate are formed (see Figure 13–5).

Step 6

H+

+ ++

glyceraldehyde 3-phosphatedehydrogenaseO H

C

CH OH

PCH2O

glyceraldehyde3-phosphate

O O

C

CH OH

P

P

CH2O

1,3-bisphosphoglycerate

NADH

NADH

H++

The transfer to ADP of the high-energy phosphate group that was generated in step 6 forms ATP.

Step 7

The remaining phosphate ester linkage in 3-phosphoglycerate, which has a relatively low free energy of hydrolysis, is moved from carbon 3 to carbon 2 to form 2-phosphoglycerate.

Step 8

The removal of water from 2-phosphoglycerate creates a high-energy enol phosphate linkage.

Step 9

The transfer to ADP of the high-energy phosphate group that was generated in step 9 forms ATP, completing glycolysis.

Step 10

NET RESULT OF GLYCOLYSIS

ATP

ATP

+pyruvate kinase

CH2OH

O

OH

OH

OHHO

glucosetwo molecules

of pyruvate

ATP

ATP

NADH ATP

ATP

ATP

In addition to the pyruvate, the net products aretwo molecules of ATP and two molecules of NADH.

1

2

3

PiNAD+

After the enzyme removes a proton from the CH3 group on acetyl CoA, the negatively charged CH2

– forms a bond to a carbonyl carbon of oxaloacetate. The subsequent loss by hydrolysis of the coenzyme A (CoA) drives the reaction strongly forward.

Step 1

An isomerization reaction, in which water is first removed and then added back, moves the hydroxyl group from one carbon atom to its neighbor.

Step 2

COO–

COO–

COO–HO

H H

H H

C

C

C

COO–

COO–

COO–

HO

H H

H

H

C

C

C

COO–

COO–

COO–

H H

H

C

C

C

citrate cis-aconitateintermediate

isocitrate

aconitase

H2O

H2O

H2O

H2O

acetyl CoA S-citryl-CoAintermediate

citrateoxaloacetate

COO–

COO–

O OCC S CoA

citratesynthase

CH3 CH2

H2OO C S CoA

CH2

COO–

COO–CHO

CH2

HS H+CoA

CH2

COO–

COO–

COO–

CHO

CH2

+ + +

Details of the eight steps are shown below. For each step, the part of the molecule that undergoes a change is shadowed in blue,and the name of the enzyme that catalyzes the reaction is in a yellow box.

CH2

COO–

COO–

COO–

CHO

CH2

H2O

H2O

H2O

CH2

CO2

CO2

CO2

COO–

COO–

COO–

HC

CHHO

CH2

COO–

COO–

C O

CH2

CH2

COO–

COO–

CH2

CH

COO–

COO–

CH

H OHC

COO–

COO–

CH2

COO–

C O

CH2

S CoA

O

CH3 S CoA

acetyl CoA

HS CoA

HS CoA

HS CoA

HS CoA

CH2

OC

COO–

COO–

CH2

O

O

C

COO–

COO–

COO–

CH2

CH3 C

next cycle

Pi

GTPGDP

+

Step 1 Step 2

Step 3

Step 4Step 6

Step 7

Step 8

Step 5

citrate (6C) isocitrate (6C)

succinyl CoA (4C)succinate (4C)

fumarate (4C)

malate (4C)

oxaloacetate (4C)

oxaloacetate (4C)

pyruvate

α-ketoglutarate (5C)+ H+

NADH

+ H+NADH

+ H+NADH

NAD+

NAD+

NAD+

+ H+NADHNAD+

FADH2

FAD

(2C)

CITRIC ACID CYCLE

The complete citric acid cycle. The two carbons from acetyl CoA that enter this turn of the cycle (shadowed in red ) will be converted to CO2 in subsequent turns of the cycle: it is the two carbons shadowed in blue that are converted to CO2 in this cycle.

C

Panel 13–2 The complete citric acid cycle

In the first of four oxidation steps in the cycle, the carbon carrying the hydroxyl group is converted to a carbonyl group. The immediate product is unstable, losing CO2 while still bound to the enzyme.

Step 3

The a-ketoglutarate dehydrogenase complex closely resembles the large enzyme complex that converts pyruvate to acetyl CoA (pyruvate dehydrogenase). It likewise catalyzes an oxidation that produces NADH, CO2, and a high-energy thioester bond to coenzyme A (CoA).

Step 4

A phosphate molecule from solution displaces the CoA, forming a high-energy phosphate linkage to succinate. This phosphate is then passed to GDP to form GTP. (In bacteria and plants, ATP is formed instead.)

Step 5

In the third oxidation step in the cycle, FAD removes two hydrogen atoms from succinate.

Step 6

The addition of water to fumarate places a hydroxyl group next to a carbonyl carbon.

Step 7

In the last of four oxidation steps in the cycle, the carbon carrying the hydroxyl group is converted to a carbonyl group, regenerating the oxaloacetate needed for step 1.

Step 8

COO–

COO–

HO

H H

H

H

C

C

C

isocitrate

isocitratedehydrogenase

CO2

COO–

COO–

COO–

H H

H

O

C

C

C

oxalosuccinateintermediate

COO–

NADHNAD+ + H+ H+

COO–

COO–

H H

H H

O

C

C

C

a-ketoglutarate

succinate dehydrogenase

FADH2FAD

COO–

COO–

H H

H H

C

C

succinate

COO–

COO–

H

H

C

C

fumarate

fumaraseCOO–

COO–

HO H

H H

C

C

malate

COO–

COO–

H

H

C

C

fumarate

H2O

a-ketoglutarate dehydrogenase complex

CO2

NADHNAD+ + H+

COO–

COO–

H H

H H

O

C

C

C

a-ketoglutarate

COO–

H H

H H

O

C

C

C

succinyl-CoA

HS CoA

S CoA

+

H2O

COO–

H H

H H

O

C

C

C

succinyl-CoA

S CoA

COO–

COO–

H H

H H

C

C

succinate

HS CoA+

succinyl-CoA synthetase

Pi GTPGDP

malate dehydrogenase

NADHNAD+ + H+

COO–

COO–

HO H

H H

C

C

malate

COO–

COO–

OC

oxaloacetate

CH2

After the enzyme removes a proton from the CH3 group on acetyl CoA, the negatively charged CH2

– forms a bond to a carbonyl carbon of oxaloacetate. The subsequent loss by hydrolysis of the coenzyme A (CoA) drives the reaction strongly forward.

Step 1

An isomerization reaction, in which water is first removed and then added back, moves the hydroxyl group from one carbon atom to its neighbor.

Step 2

COO–

COO–

COO–HO

H H

H H

C

C

C

COO–

COO–

COO–

HO

H H

H

H

C

C

C

COO–

COO–

COO–

H H

H

C

C

C

citrate cis-aconitateintermediate

isocitrate

aconitase

H2O

H2O

H2O

H2O

acetyl CoA S-citryl-CoAintermediate

citrateoxaloacetate

COO–

COO–

O OCC S CoA

citratesynthase

CH3 CH2

H2OO C S CoA

CH2

COO–

COO–CHO

CH2

HS H+CoA

CH2

COO–

COO–

COO–

CHO

CH2

+ + +

Details of the eight steps are shown below. For each step, the part of the molecule that undergoes a change is shadowed in blue,and the name of the enzyme that catalyzes the reaction is in a yellow box.

CH2

COO–

COO–

COO–

CHO

CH2

H2O

H2O

H2O

CH2

CO2

CO2

CO2

COO–

COO–

COO–

HC

CHHO

CH2

COO–

COO–

C O

CH2

CH2

COO–

COO–

CH2

CH

COO–

COO–

CH

H OHC

COO–

COO–

CH2

COO–

C O

CH2

S CoA

O

CH3 S CoA

acetyl CoA

HS CoA

HS CoA

HS CoA

HS CoA

CH2

OC

COO–

COO–

CH2

O

O

C

COO–

COO–

COO–

CH2

CH3 C

next cycle

Pi

GTPGDP

+

Step 1 Step 2

Step 3

Step 4Step 6

Step 7

Step 8

Step 5

citrate (6C) isocitrate (6C)

succinyl CoA (4C)succinate (4C)

fumarate (4C)

malate (4C)

oxaloacetate (4C)

oxaloacetate (4C)

pyruvate

α-ketoglutarate (5C)+ H+

NADH

+ H+NADH

+ H+NADH

NAD+

NAD+

NAD+

+ H+NADHNAD+

FADH2

FAD

(2C)

CITRIC ACID CYCLE

The complete citric acid cycle. The two carbons from acetyl CoA that enter this turn of the cycle (shadowed in red ) will be converted to CO2 in subsequent turns of the cycle: it is the two carbons shadowed in blue that are converted to CO2 in this cycle.

C

Panel 13–2 The complete citric acid cycle

In the first of four oxidation steps in the cycle, the carbon carrying the hydroxyl group is converted to a carbonyl group. The immediate product is unstable, losing CO2 while still bound to the enzyme.

Step 3

The a-ketoglutarate dehydrogenase complex closely resembles the large enzyme complex that converts pyruvate to acetyl CoA (pyruvate dehydrogenase). It likewise catalyzes an oxidation that produces NADH, CO2, and a high-energy thioester bond to coenzyme A (CoA).

Step 4

A phosphate molecule from solution displaces the CoA, forming a high-energy phosphate linkage to succinate. This phosphate is then passed to GDP to form GTP. (In bacteria and plants, ATP is formed instead.)

Step 5

In the third oxidation step in the cycle, FAD removes two hydrogen atoms from succinate.

Step 6

The addition of water to fumarate places a hydroxyl group next to a carbonyl carbon.

Step 7

In the last of four oxidation steps in the cycle, the carbon carrying the hydroxyl group is converted to a carbonyl group, regenerating the oxaloacetate needed for step 1.

Step 8

COO–

COO–

HO

H H

H

H

C

C

C

isocitrate

isocitratedehydrogenase

CO2

COO–

COO–

COO–

H H

H

O

C

C

C

oxalosuccinateintermediate

COO–

NADHNAD+ + H+ H+

COO–

COO–

H H

H H

O

C

C

C

a-ketoglutarate

succinate dehydrogenase

FADH2FAD

COO–

COO–

H H

H H

C

C

succinate

COO–

COO–

H

H

C

C

fumarate

fumaraseCOO–

COO–

HO H

H H

C

C

malate

COO–

COO–

H

H

C

C

fumarate

H2O

a-ketoglutarate dehydrogenase complex

CO2

NADHNAD+ + H+

COO–

COO–

H H

H H

O

C

C

C

a-ketoglutarate

COO–

H H

H H

O

C

C

C

succinyl-CoA

HS CoA

S CoA

+

H2O

COO–

H H

H H

O

C

C

C

succinyl-CoA

S CoA

COO–

COO–

H H

H H

C

C

succinate

HS CoA+

succinyl-CoA synthetase

Pi GTPGDP

malate dehydrogenase

NADHNAD+ + H+

COO–

COO–

HO H

H H

C

C

malate

COO–

COO–

OC

oxaloacetate

CH2