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THE NATURE OF CARBOHYDRATES

CARBOHYDRATE STRUCTURE AND METABOLISM
I. CARBOHYDRATES PROVIDE READY ENERGY, STORED ENERGY,
STRUCTURAL COMPONENTS, AND PRECURSORS OF FATS, PROTEINS
AND NUCLEIC ACIDS

Carbohydrates, the primary products of photosynthesis, are abundant in nature. As an
energy source, carbohydrates comprise 50% of the average daily caloric intake for Americans.
Carbohydrates also serve as stored energy reserves, in the form of glycogen in animals and starch
in plants; glucose can be released from these storage forms for immediate use as fuel.
Carbohydrates are important in tissue structure components (as polysaccharides, glycoproteins
and glycolipids) in cell membranes and in intercellular materials. They also provide precursors
for biosynthesis of proteins, nucleic acids and lipids and other biochemical materials.
II. CARBOHYDRATES ARE MONOMERS OR POLYMERS OF POLYHYDROXY-
ALDEHYDES OR KETONES
A. Monosaccharides
These simple sugars may be joined in short chains as oligosaccharides (about 2-10 units) or in long
linear or branched chains as polysaccharides. The general formula of a monosaccharide is (CH
2
O)
n

where n3 or more. The fundamental structure is a linear polyhydroxy-aldehyde (aldose) or -
ketone (ketose).

Both of the monosaccharides in the
figure are trioses, i.e 3-carbon
sugars. From each triose formula, it
is possible to generate the formulae
for a series of sugars by adding
hydroxylated carbon atoms to the
chain to form tetroses (4 carbon
atoms); pentoses (5); hexoses (6); or
heptoses (7). These numerical
designations may be combined with
a prefix from aldose or ketose to form terms such as aldohexose, ketopentose, to describe a
monosaccharide.


B. Asymmetric carbons in sugars yield stereoisomers
Glyceraldehyde has one asymmetric carbon atom, and there are two different isomers of

Fig. 1 Trioses:
Fig. 2 D(R) and L(S) isomers:

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this triose. They are named D- and L-glyceraldehyde (or, R- and S-glyceraldehyde), and are
represented in Figure 2.

Dihydroxyacetone has no asymmetric carbon atom, but longer ketoses do have one or
more. As the carbon skeleton is elongated, larger numbers of isomeric monosaccharides are
possible. Figures 3 and 4 show how physiologically important sugars are structurally related to
D-glyceraldehyde or dihydroxyacetone.
Figure 3 shows structures of only physiologically important sugars. That is, only three of
the 4 aldopentoses in the D-series are presented, and only 3 of the 8 aldohexoses. The arrows
show relationships between sugars of a given size and the structures formed by adding one more
H-CO-H or HO-C-H to the carbon chain. For example, the 3,4,5 and 6-carbons of the hexoses
D-glucose and D-mannose are identical to the 2,3,4, and 5-carbons of the pentose D-arabinose. -
and all of them have CHO at the 1-carbon. Going from pentose to hexose, one C has been added,
Fig. 3 Aldoses

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at the 2-position. D-glucose and D-mannose differ only in the conformation of substituents at
that 2-position: H-C-OH in glucose and HO-C-H in mannose.



Once again, only 1 of the 4 possible ketohexoses is shown. Note that hexoses have one
less asymmetric carbon than aldoses of the same length, so there are fewer ketose isomers than
aldose isomers for a given length.

C. Aldoses and ketoses are reducing agents

The aldehyde and ketone functions of sugars are chemically reactive. For example, they
can donate electrons to other substances (i.e. reduce other substances); in the process, the
sugars are oxidized. The aldehyde or ketone is called the "reducing end" of the sugar, and the
Fig. 4. Ketoses

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opposite end, bearing a hydroxyl group, is the "non-reducing end". The ability of a sugar to
reduce cupric ion is the basis of a chemical assay for monosaccharides or terminal residues of
carbohydrate chains.


D. Monosaccharides are numbered beginning at the most oxidized end.

Some examples are:


The asymmetric carbon of the highest number determines the D or L configuration. If it is
related to D-glyceraldehyde, the sugar is a D-isomer. Most monosaccharides in nature are D-
isomers. D- and L-isomers are mirror images. L-ribose, for example, differs from D-ribose
not only at carbon-4 but at every asymmetric carbon and therefore is a mirror image of D-
ribose. Epimers are isomers that differ in configuration at only one asymmetric carbon atom:





Fig. 5. Numbering of C atoms
Fig. 6. Stereoisomers of pentoses

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The maximum number of stereoisomers of a ketose or aldose of given carbon chain
length can be predicted by the formula

2
n
= number of stereoisomers

where n= the number of asymmetric carbon atoms. Ketoses have one less asymmetric carbon
than do aldoses of the same length. Hence the number of aldohexose stereoisomers is 16. Of
these, 8 are D-isomers and 8 are L-isomers. The number of ketohexose stereoisomers is 8 (4 D-
isomers and 4 L-isomers).

E. Sugars occur mainly as closed ring structures rather than open chains

In aqueous solution, many monosaccharides form 5- and 6-membered rings, by an
intramolecular formation of a hemiacetal or hemiketal.

1. Hemiacetal formation occurs in ring formation of aldoses, as follows:


Both the aldehyde and the alcohol are parts of the same molecule. Aldohexoses such as
glucose form 6-membered rings, called pyranoses because of their similarity to the cyclic
compound pyran. Ring formation involves the C1 aldehyde and the C5 alcohol.

2. Hemiketal formation occurs in ring formation of ketoses, as follows:


Ketohexoses form 5-membered rings, which are called furanoses because of their
similarity to the compound furan, or 6-membered pyranose rings. Ring formation involves the
C2 carbonyl and the C5 alcohol (furanose) or C6 alcohol (pyranose). Nuclear magnetic
resonance analysis of sugars in honey indicates that about 67% of fructose is present as a
pyranose and 33% as furanose.


F. Ring closure forms an additional asymmetric carbon.


Fig. 7. Aldose ring formation
Fig 8. Ketose ring formation

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With the formation of a closed ring, another asymmetric carbon is formed at carbon-1 in
aldoses or carbon 2 in ketoses, as the substituents of this carbon in the ring can occupy two
different positions. These closed rings are termed and isomers, as in -D- and -D-
glucopyranoses ( -D- and -D-glucose). The and isomers are anomers; carbon-1 in an
aldose (or carbon 2 in a ketose) is the anomeric carbon. The and isomers rotate polarized
light in opposite directions (Fig. 9). The anomers are inter-convertible. A solution that may start
at 100% " isomer or isomer of D-glucose gradually changes to an equilibrium mixture, usually
about 60% anomer, 40% " anomer, and less than 1% in the open chain form, which is an
intermediate in the interconversion between and forms.





A commonly used depiction of sugars in ring forms is the Haworth projection. The
Haworth projection for -D-glucopyranose is depicted below:













The anomer has the hydroxyl group of the anomeric carbon on the same side of the ring
as the highest numbered carbon, and the anomer has this hydroxyl group on the opposite side
of the ring. The other substituents are oriented downward if they appear to the right of the carbon
in the chain form, and upward if they appear to the left of the carbon in the chain form.


Fig. 9. Mutarotation; optical
activity of D- and L-isomers


Fig. 10 Haworth projection of -D-glucose

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The actual shape of the pyranose ring is a "boat" form or a "chair" form, since the 6-
membered ring cannot be planar. The chair form is more stable, having less steric interference
among the substituents on the ring carbons. The substituents are more precisely labeled as axial
(a) or equatorial (e) in orientation rather than as upward or downward as in the Haworth
projection.


Aldopentoses and ketohexoses in the 5-membered furanose ring form are represented by the
following Haworth projections:












Furanoses also have and anomers; again, the anomer has the anomeric hydroxyl group on
the same side of the ring as the highest numbered carbon (carbon 5 in aldopentoses and carbon 6
in ketohexoses). The 5-member ring cannot be perfectly planar. Puckering occurs, with carbon 2
and carbon 3 out of the plane formed by the other carbons and the oxygen of the ring. The carbon
2 and carbon 3 atoms are out of the plane in opposite directions.










G. Monosaccharides of physiological importance
Several monosaccharides are of particular importance and appear frequently in studies of
metabolism.


Fig. 11. Non-planar hexose (pyranose form) rings


Fig. 12. Haworth projections of furanose forms




D-Ribose





Structural component of RNA.
Appears in many nucleotide
Coenzymes (NAD, FAD)


Haworth Projection Occurrence and important roles

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III. SUGAR DERIVATIVES ARE IMPORTANT INTERMEDIATES IN METABOLISM

A. Sugar alcohols. The carbonyl group of monosaccharides may be reduced to a
hydroxyl group.

1. Glycerol, formed by reduction of D-glyceraldehyde, is the backbone of many lipids.









2. D-sorbitol, from the reduction of either glucose or fructose, is an intermediate in the synthesis
of fructose from glucose, especially in the prostate gland.















3. Myoinositol, present as a phosphate ester in some phospholipids, notably in the brain;
inositol-phosphate derivatives are important regulatory molecules involved in cell responses to
growth factors.












Fig 14. Glycerol


Fig. 15. D-sorbitol
Fig. 16.

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B. Sugar acids:

1. Uronic acids result from the oxidation of the non-reducing terminal
carbon to COOH, as in D-glucuronic acid, which occurs in polymers
in intercellular material such as joint fluid and vitreous fluid of the
eye. Glucuronic acid also plays an important role in the metabolism
and excretion of certain insoluble metabolites and drugs. For example,
liver enzymes attach glucuronic acid to bilirubin, a product of the
breakdown of heme, making the bilirubin water- soluble and
facilitating its excretion into bile.








2. Aldonic acids result from the oxidation of the aldehyde of aldoses, as in D-
gluconic acid. The phosphate ester of D-gluconic acid is an important
intermediate in the formation of pentoses from glucose.











3. Ascorbic acid (Vitamin C) is a lactone of a hexonic acid. It is an
essential nutrient for humans and guinea pigs. Ascorbic acid participates
in oxidation- reduction reactions, and in the addition of hydroxyl groups to
proline and lysine in the formation of collagen.














Fig. 17. D-glucuronic acid


Fig. 18. D-gluconic acid


Fig. 19. Ascorbic acid

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C. Sugar phosphates. The first step in the metabolism of a monosaccharide is its activation by
transfer of a phosphate group from ATP to the sugar to form a sugar-phosphate ester. Many
intermediates of carbohydrate metabolism are phosphorylated sugar derivatives.










D. Deoxysugars.
These sugars lack one hydroxyl group. Most abundant is 2-deoxyribose, which is the pentose
moiety in DNA. Other examples are fucose and rhamnose (6-deoxy sugars), which are present
in cell surface glycoproteins.













E. Aminosugars. The carbon 2 of glucose or galactose may carry an amino group as a
substituent instead of a hydroxyl group to form glucosamine or galactosamine. These sugars are
important components of glycoproteins, membranes, and bacterial cell walls. The amino group is
frequently acetylated. Sialic acid is a more complex aminosugar that occurs at the free terminus
of polysaccharide chains on many glycoproteins.







Fig. 21. Deoxysugars

Fig. 22. Aminosugars
Fig. 20. Sugar phosphate esters