09/16/08Biochemistry: Carbohydrates 1 Carbohydrates Andy Howard Introductory Biochemistry, Fall 2008 16 September 2008

09/16/08Biochemistry: Carbohydrates 1

Carbohydrates

Andy HowardIntroductory Biochemistry, Fall 2008

16 September 2008

09/16/08 Biochemistry: Carbohydrates p. 2 of 66

Now we’ll study sugars!

Sugars are vital as energy sources, and they also serve as building blocks for lipid-carbohydrate and protein-carbohydrate complexes


What we’ll discuss

Notes about upcoming midterm

Sugar Concepts Monosaccharides Oligosaccharides Glycosides

Polysaccharides Starch & glycogen Cellulose and chitin

Glycoconjugates Proteoglycans Peptidoglycans Glycoproteins


Midterm is Tuesday 23 Sep

Internet students can take it between 9am Tuesday and 5pm Wednesday

Find a proctor or arrange to take it in class

Details about how the midterm works are in the Course Introduction document


What the midterm will cover Everything up through today’s lecture Thursday’s lecture will be on the second

midterm Exam syllabus will be posted by the

weekend to help you study Exam help-sheet too (don’t memorize

what’s on the help sheet!) Yes, I curve these exams; but the grade

cutoffs are determined at the end of the course, not now


Carbohydrates These are polyhydroxylated aldehydes and

ketones, many of which can exist in cyclic forms General monomeric formula (CH2O)m, 3 < m < 9 With one exception (dihydroxyacetone) they

contain chiral centers Highly soluble Can be oligomerized and polymerized Oligomers may or may not be soluble Most abundant organic molecules on the planet


How do we measure solubility for very soluble compounds?

(Note: this is not a serious chemical topic: it’s an example of how statistics can be abused…)

The assertion is that, with highly soluble compounds like sugars, it’s difficult to use conventional approaches to compare their solubilities

The suggestion is that we might use the amount of time it takes to dissolve (for example) 50g of solute in 100mL of cold water: if it’s fast, the solute is more soluble than if it’s slow.


Solubility measured by dissolution time

Assertion: more polar groups means shorter dissolution time for a given class of compounds

# of

pol

ar g

roup

s

Time required for dissolution

1

2

3

4

5

6


What if we extrapolate to n=6?

We get a negative dissolution time!

That is, the solid goes into solution 6 seconds before we put it in the water!

This causes serious psychological problems (what if I change my mind?) and philosophical problems (is this pre-ordained?)

# of

pol

ar g

roup

s

Time required for dissolution

1

2

3

4

5

6

Observed points

Extrapolated point


Whose idea is this? Isaac Asimov, that’s who! “The endochronic properties of resublimated

thiotimolene”:Astounding Science Fiction, March1948

My point: extrapolations and other misuses of statistics are dangerous

Benjamin Disraeli (popularized by Mark Twain):There are three kinds of untruth:lies, damn lies, and statistics.

Okay: let’s get back to the science.


Aldoses & ketoses If the carbonyl moiety is at

the end carbon (conventionally counted as 1), it’s an aldose

If carbonyl is one carbon away (counted as 2), it’s a ketose

If it’s two or more carbons from the end of the chain, it’s not a sugar


Simplest monosaccharides Glyceraldehyde and

dihydroxyacetone Only glyceraldehyde is chiral:

D-enantiomer is more plentiful in biosphere

All longer sugars can be regarded as being built up by adding-(CHOH)m-1 to either glyceraldehyde or dihydroxyacetone, just below C2


How many aldoses are there? Every -(CHOH) in the interior offers one

chiral center An m-carbon aldose has (m-2) internal

-(CHOH) groups Therefore: 2m-2 aldoses of length m For m=3, that’s 21=2; for m=6, it’s 24=16.


How many ketoses are there? Every -(CHOH) in the interior offers

one chiral center An m-carbon ketose has (m-3) internal

-(CHOH) groups Therefore: 2m-3 ketoses of length m For m=3, that’s 20 = 1; for m=6, that’s

23=8.


Review: stereochemical nomenclature Stereoisomers: compounds with identical

covalent bonding apart from chiral connectivity Enantiomers: compounds for which the opposite

chirality applies at all chiral centers Epimers: compounds that differ in chirality at

exactly one chiral center One chiral center: enantiomers are epimers. > 1 chiral center: enantiomers are not epimers.


Example: 2 chiral centers Chiral centers u,v; compounds A,B,C,D

Compound Stereo @ u

Stereo @ v

Enantio-morph of

Epimer of

A + + D B,C

B + - C A,D

C - + B A,D

D - - A B,C


Properties

Enantiomers have identical physical properties (MP,BP, solubility, surface tension…) except when they interact with other chiral molecules

(Note!: water isn’t chiral!) Stereoisomers that aren’t enantiomers

can have different properties; therefore, they’re often given different names


Sugar nomenclature

All sugars with m ≤ 7 have specific names apart from their enantiomeric(L or D) designation,e.g. D-glucose, L-ribose.

The only 7-carbon sugar that routinely gets involved in metabolism is sedoheptulose, so we won’t try to articulate the names of the others


Fischer projections Convention for drawing open-

chain monosaccharides If the hydroxyl comes off

counterclockwise relative to the previous carbon, we draw it to the left;

Clockwise to the right.

Emil Fischer


Cyclic sugars Sugars with at least four carbons can

readily interconvert between the open-chain forms we have drawn and five-membered(furanose) or six-membered (pyranose) ring forms in which the carbonyl oxygen becomes part of the ring

There are no C=O bonds in the ring forms


Furanoses Formally derived from

structure of furan Hydroxyls hang off of the

ring; stereochemistry preserved there

Extra carbons come off at 2 and 5 positions

3

2

1

4

5

furan


Pyranoses Formally derived from

structure of pyran Hydroxyls hang off of the

ring; stereochemistry preserved there

Extra carbons come off at 2 and 6 positions

3

2

4

5

1

6

pyran


How do we cyclize a sugar?

Formation of an internal hemiacetal or hemiketal (see a few slides from here) by conversion of the carbonyl oxygen to a ring oxygen

Not a net oxidation or reduction;in fact it’s a true isomerization.

The molecular formula for the cyclized form is the same as the open chain form


Family tree of aldoses

Simplest: D-, L- glyceraldehyde (C3) Add —CHOH: D,L-threose, erythrose (C4) Add —CHOH:

D,L- lyxose, xylose, arabinose, ribose (C5) Add —CHOH:

D,L-talose, galactose, idose, gulose,mannose, glucose, altrose, allose (C6)


Family tree of ketoses

Simplest: dihydroxyacetone (C3) Add —CHOH: D,L-erythrulose (C4) Add —CHOH:

D,L- ribulose, xylulose (C5) Add —CHOH:

D,L-sorbose, tagatose, fructose, psicose (C6)


Haworth projections

…provide a way of keeping track the chiral centers in a cyclic sugar, as the Fischer projections enable for straight-chain sugars

Sir Walter Haworth


The anomeric carbon

In any cyclic sugar (monosaccharide, or single unit of an oligosaccharide, or polysaccharide) there is one carbon that has covalent bonds to two different oxygen atoms

We describe this carbon as the anomeric carbon

C

O

O


iClicker quiz, question 1 Which of these is a furanose sugar?


iClicker quiz, question 2

Which carbon is the anomeric carbon in this sugar?

(a) 1 (b) 2 (c) 5 (d) 6 (e) none of these.


iClicker, question 3

How many 7-carbon D-ketoses are there?

(a) none. (b) 4 (c) 8 (d) 16 (e) 32


-D-glucopyranose

One of 2 possible pyranose forms of D-glucose

There are two because the anomeric carbon itself becomes chiral when we cyclize


-D-glucopyranose

Differs from -D-gluco-pyranose only at anomeric carbon


Count carefully!

It’s tempting to think that hexoses are pyranoses and pentoses are furanoses;

But that’s not always true The ring always contains an oxygen, so

even a pentose can form a pyranose In solution: pyranose, furanose, open-

chain forms are all present Percentages depend on the sugar


Substituted monosaccharides Substitutions on the various positions

retain some sugar-like character Some substituted monosaccharides are

building blocks of polysaccharides Amination, acetylamination,

carboxylation common

O

OH

HO

HO

HNCOCH3

OH

OHO

HO

HOOH

O O-

GlcNAcD-glucuronic acid(GlcUA)


Sugar acids (fig. 7.10)

Gluconic acid: glucose carboxylated @ 1 position In equilibrium with lactone form

Glucuronic acid:glucose carboxylated @ 6 position

Glucaric acid:glucose carboxylated @ 1 and 6 positions

Iduronic acid: idose carboxylated @ 6

D--gluconolactone

1

2

5

3

4

6


Sugar alcohols (fig.7.11) Mild reduction of sugars convert aldehyde

moiety to alcohol Generates an additional asymmetric

center in ketoses These remain in open-chain forms Smallest: glycerol Sorbitol, myo-inositol, ribitol are important


Sugar esters (fig. 7.13)

Phosphate esters of sugars are significant metabolic intermediates

5’ position on ribose is phosphorylated in nucleotides

Glucose 6-phosphate


Amino sugars

Hydroxyl at 2- position of hexoses is replaced with an amine group

Amine is often acetylated (CH3C=O) These aminated sugars are found in

many polysaccharides and glycoproteins

O

OH

HO

HO

HNCOCH3

OHGlcNAc


Acetals and ketals Hemiacetals and hemiketals are compounds that

have an –OH and an –OR group on the same carbon Cyclic monosaccharides are hemiacetals &

hemiketals Acetals and ketals have two —OR groups on a single

carbon Acetals and ketals are found in glycosidic bonds


Oligosaccharides and other glycosides A glycoside is any compound in which

the hydroxyl group of the anomeric carbon is replaced via condensation with an alcohol, an amine, or a thiol

All oligosaccharides are glycosides, but so are a lot of monomeric sugar derivatives, like nucleosides


Sucrose: a glycoside

A disaccharide Linkage is between

anomeric carbons of contributing monosaccharides, which are glucose and fructose


Other disaccharides Maltose

glc-glc with -glycosidic bond from left-hand glc Produced in brewing, malted milk, etc.

Cellobiose -glc-glc Breakdown product from cellulose

Lactose: -gal-glc Milk sugar Lactose intolerance caused by absence of

enzyme capable of hydrolyzing this glycoside


Reducing sugars Sugars that can undergo ring-opening to

form the open-chain aldehyde compounds that can be oxidized to carboxylic acids

We describe those as reducing sugars because they can reduce metal ions or amino acids in the presence of base

Benedict’s test:2Cu2+ + RCH=O + 5OH- Cu2O + RCOO- + 3H2O

Cuprous oxide is red and insoluble


Ketoses are reducing sugars In presence of base a ketose can

spontaneously rearrange to an aldose via an enediol intermediate, and then the aldose can be oxidized.


Sucrose: not a reducing sugar Both anomeric carbons

are involved in the glycosidic bond, so they can’t rearrange or open up, so it can’t be oxidized

Bottom line: only sugars in which the anomeric carbon is free are reducing sugars


Reducing & nonreducing ends Typically, oligo and polysaccharides have a

reducing end and a nonreducing end Non-reducing end is the sugar moiety

whose anomeric carbon is involved in the glycosidic bond

Reducing end is sugar whose anomeric carbon is free to open up and oxidize

Enzymatic lengthening and degradation of polysaccharides occurs at nonreducing end or ends


Nucleosides Anomeric carbon of

ribose (or deoxyribose) is linked to nitrogen of RNA (or DNA) base (A,C,G,T,U)

Generally ribose is in furanose form

This is an example of an N-glycoside Diagram courtesy of

World of Molecules


Polysaccharides Homoglycans: all building blocks same Heteroglycans: more than one kind of

building block No equivalent of genetic code for

carbohydrates, so long ones will be heterogeneous in length and branching, and maybe even in monomer identity


Categories of polysaccharides Storage homoglycans (all Glc)

Starch: amylose ((14)Glc) , amylopectin Glycogen

Structural homoglycans Cellulose ((14)Glc) Chitin ((14)GlcNac)

Heteroglycans Glycosaminoglycans (disacch.units) Hyaluronic acid (GlcUA,GlcNAc)((1 3,4))


Storage polysaccharides

Available sources of glucose for energy and carbon

Long-chain polymers of glucose Starch (amylose and amylopectin):

in plants, it’s stored in 3-100 µm granules Glycogen Branches found in all but amylose


Amylose Unbranched, -14 linkages Typically 100-1000 residues Not soluble but can form hydrated

micelles and may be helical Amylases hydrolyze -14 linkages

Diagram courtesyLangara College


Amylopectin Mostly -14 linkages; 4% -16 Each sidechain has 15-25 glucose

moieties -16 linkages broken down by

debranching enzymes 300-6000 total glucose units per

amylopectin molecule One reducing end, many nonreducing

ends


Glycogen Principal storage form of glucose in

human liver; some in muscle Branched (-14 + a few -16) More branches (~10%) Larger than starch: 50000 glucose One reducing end, many nonreducing

ends Broken down to G-1-P units Built up from

G-6-P G-1-P UDP-Glucose units


Glycogen structure

Documents

09/16/08Biochemistry: Carbohydrates 1 Carbohydrates Andy Howard Introductory Biochemistry, Fall 2008 16 September 2008