5. Carbohydrates: mono-, di- and poly-saccharides
Question 61. What compounds are called carbohydrates?
Answer. Carbohydrates are class of natural organic substances which are hetero-functional compounds containing simultaneously carbonyl and hydroxyl functional groups (i.e., they are multi-atom aldehydo- or keto-alcohols or their condensation products). The term “carbohydrates” appeared in the middle of 19th century as in their molecules relation between hydrogen atoms and oxygen atoms is the same as in water molecule, in other words, two hydrogen atoms correspond to one oxygen atom and carbohydrate molecule could be represented as build from carbon (coal) and water. For example, glucose molecule (С6Н12О6) has the following form С6(Н2О)6, sucrose formula (С12Н22О11) could be written as С12(Н2О)11, and in general form it is Сn(Н2О)m. Later natural carbohydrates were discovered which do not correspond to the general formula (Сn(Н2О)m), but the term “carbohydrates” is used at present together with the term “saccharides” or “sugars”.
Question 62. What are carbohydrate functions?
Answer. Carbohydrates are formed at plants as a result of photo-synthesis from carbon di-oxide and water. Animal organisms are not able to produce carbohydrates and receive them with plant food. Thus, carbohydrates are in the structure of all living organisms and they are most widely-spread organic substances on Earth. Carbohydrate functions:
– structural and supportive functions (cellulose is main structural element of cellular walls at plants, chitin has similar function at fungus and provides solid character of exo-skeleton at arthropod and similar animals);
– protective function (at some plants there are protective formations: thorns, prickles etc. which are made from dead cells cellular walls;
– energy function (at 1 gr of carbohydrate oxidation 4,1 kcal of energy is discharged);
– plastic function (they are in the structure of complex molecules, for example, ribose and deoxyribose, take part at ATP, DNA and RNA structure);
– keeping function (carbohydrates store nutrition substances: glycogen at animals, starch and inulin at plants);
– osmotic function (they take part at osmotic pressure regulation in the organism, including blood);
– receptor function (they are in the structure of perceiving part at many cellular receptors).
Many carbohydrates and their derivatives are used at pharmacy and medicine. Carbohydrates are initial substances for paper, artificial fibers, explosives, ethyl alcohol production etc.
Question 63. What is carbohydrate classification?
A
nswer.
Carbohydrates are subdivided into two classes: un-conjugated (simple)
and conjugated (complex). Unconjugated carbohydrates
(mono-saccharides, monoses) are not hydrolyzed with more simple
carbohydrate formation. Unconjugated carbohydrates are, for example,
glucose (С6Н12О6),
ribose (С5Н10О5),
fructose (С6Н12О6).
D
– fructose
D
– glucose
D
– ribose
Unconjugated carbohydrates containing keto-group are called ketoses, containing aldehyde group are called aldoses. According to carbon atom numbers monoses are subdivided into trioses (three carbon atoms), tetroses (four carbon atoms), pentoses (five carbon atoms), hexoses (six carbon atoms) and heptoses (seven carbon atoms).
For example, glucose contains aldehyde group and six carbon atoms, it is called aldohexose. Fructose has carbonyl group (it is poly-keto-alcohol) and six carbon atoms, it is called keto-hexose. Ribose is aldopentose. Natural monoses, as a rule, have un-branched carbon chains.
C
D
– фруктоза
D
– фруктоза
D
– фруктоза
If at carbohydrate hydrolysis large amount of unconjugated carbohydrates are formed (up to several thousands) then these carbohydrates are called poly-saccharides. Poly-saccharides are high-molecular compounds. They include starch and cellulose (cellular tissue). Conjugated carbohydrates could be looked at as mono-saccharide poly-condensation products.
If poly-saccharides have one mono-saccharide residues then it is called homo-poly-saccharide, if there are different mono-saccharide residues then they are called hetero-poly-saccharides.
Biologically important homo-poly-saccharides are starch, glycogen and cellulose. Biologically important hetero-poly-saccharides are algene acids, agar which is in the structure of sea weeds. Poly-saccharides of connective tissue are chondroitin-sulfates, hyaluronic acid, and heparin).
Carbohydrate molecules are in the structure of mixed biopolymers (glyco-proteins, proteo-glycanes) or carbon-lipids (glyco-lipids).
Question 64. Are mono-saccharides optically active compounds? Write enantiomers for mono-saccharides.
Answer. Mono-saccharide molecules (except di-oxy-acetone) have chirality centres (contain asymmetric carbon atoms) which is the reason for their stereo-isomers existence. For example, aldohexose has four asymmetric carbon atoms and it has 16 stereo-isomers (24 = 16), forming 8 pairs. At aldopentose there are three asymmetric carbon atoms and it has 8 stereo-isomers (23 = 8), forming 4 pairs.
M
embers
of one pair are antipodes or enantiomers (their molecules refer to
each other as an object and its mirror reflection). Enantiomers have
one and the same name but one of them belongs to D-series and another
belongs to L-series. Enantiomers could be represented in the form of
open Fischer’s formulas, for example:
At Fischer’s formulas carbon chain is written vertically and enumeration starts from the end to which aldehyde or keto-group is closer, i.e. from highest carbon atom. Asymmetric carbon atoms are not marked by symbol “C”, it is supposed that they are located on the crossing of vertical and horizontal lines.
K
eto-pentose
molecule has two asymmetric carbon atoms (the third and the fourth)
and forms two pairs of enantiomers:
Isomer belonging to D- or L-series is determined by configuration comparison: it is the farthest asymmetric carbon atom located in relation to carbonyl group, it is compared to isomer configuration of glycerol aldehyde which is considered to be the standard. Glycerol aldehyde has one asymmetric carbon atom in the molecule and has only two enantiomers:
D
– glycerol aldehyde
L
– glycerol aldehyde
Let’s analyze fructose isomers as an example:
D
– fructose
In each formula there are three asymmetric (chiral) carbon atoms. These are atoms 3, 4 and 5. The farthest from keto-group (С=О) are chiral atoms with number 5. At formula (1) fifth carbon atom configuration corresponds to chiral atom configuration at D-glycerol aldehyde (ОН group is located at the right, hydrogen atom is located at the left). Thus, first isomer belongs to D-series, it is D-fructose. Fifth carbon atom configuration at formula (2) corresponds to L-glycerol aldehyde configuration, it is L-fructose. Majority of natural mono-saccharides belongs to D-series.
Question 65. Are there free mono-saccharides at natural conditions?
Answer. The most widely-spread natural mono-saccharide is D-glucose - grape sugar or dextrose from Latin “dexrus” - right, as usual natural D-glucose has specific rotation + 52,5о, i.e. rotates the polarization plane of plane-polarized light to the right on 52,5о .
In free form it is at blood being energy substrate for brain. Glucose constant level is kept with the help of insulin hormone, which decreases glucose concentration in blood and also there is glucagon, adrenalin and other hormones which increase its concentration. At diabetes mellitus insulin is produced at pancreas and its amount is not sufficient which leads to glucose concentration increase in blood.
It is interesting that L-glucose being usual natural D-glucose enantiomer is also sweet but it is not utilized in the organism that is why, it could not be used as sugar substitute.
Free glucose is at green plant parts, at different fruits and honey. It is in starch, glycogen, cellulose, hemi-cellulose, dextranes, sucrose, maltose and many other glycoside structures.
D-fructose is fruit sugar or levulose from Latin “laevus” - left as D-fructose aqueous solutions have specific rotation - 92,4o.
Fructose is at green plant parts, flowers, fruits and honey. It is in the structure of sucrose and many poly-saccharides.
D-galactose. In free crystal form it is discharged at ivy fruit. It is used as part at some di-saccharides (lactose) and poly-saccharides (chondroitin, agar-agar, mucosa, hemi-cellulose).
Question 66. Write down galactose L-isomer if D-isomer formula is known.
Answer. To write down enantiomer formula it is necessary to write mirror reflection of all substitutes at all asymmetric carbon atoms. Let’s write down D-galactose formula taking it from the scheme, which is located lower, and change substitute location (–Н and –ОН) at 2, 3, 4 and 5 carbon atoms:
As
a result we get D-galactose enantiomer:
НО
Н
Н
Н
НО
ОН
Н
ОН
НО
Н
Н
ОН
Н
Н
ОН
НО
СН2ОН
СН2ОН
D
– galactose
L
– galactose
Enantiomer name is L-galactose.
Question 67. What is the difference in dia-stereomers, epimers and enantiomers?
Answer. Carbohydrate stereo-isomers which differ from each other in configuration of only one or several asymmetric carbon atoms are called dia-stereomers, for example, D-allose and D-mannose; D-fructose and L-tagatose etc.
Epimers and enantiomers are certain cases of dia-stereomers.
Dia-stereomers which refer to each other as object and its mirror reflection are called enantiomers. Enantiomers have same physical and chemical properties but they differ from each other only by polarization plane rotation direction of plane-polarized light. Enantiomer biological activity is also different.
If dia-stereomers differ in configuration of only one asymmetric carbon atom then they are called epimers. If configuration differs at second carbon atom then such dia-stereomers are called just epimers; if difference is at some other atoms then this atom number is added to the name.
For example, D-ribose and D-arabinose differ from each other in configuration of the second carbon atom and they are epimers.
D-allose and D-glucose differ from each other in configuration of the third carbon atom that is why, they are 3-epimers; D-allose and D-gulose are 4-epimers.
Epimers have different physical and chemical properties and different biological activity.
Question 68. Are D-allose and L-idose dia-stereomers?
Answer. To answer the question it is necessary to write these aldoses formulas. D-allose formula is represented in the table (question 66). L-idose is D-idose enantiomer, i.e. their molecules refer to each other as an object and its mirror reflection. If you know D-idose formula it is easy to write down L-idose formula (question 66):
According to definition dia-stereomers should differ from each other in configuration at one or several asymmetric carbon atoms. Analyzing D-allose and L-idose formulas we conclude that they have same configurations at the second and the fourth carbon atoms (at D-allose formula and at L-idose formula OH groups are located at the right and hydrogen atoms are located at the left).
Configuration at the third and fifth carbon atoms is different (at D-allose molecule OH groups are located at the right in relation to carbon chain and at the molecule of L-idose they are located at the left). Thus, D-allose and L-idose differ in configuration of two asymmetric carbon atoms: the third and the fifth, and they are dia-stereomers.
Question 69. Are D-glucose and D-mannose epimers?
A
nswer.
To answer this question it is necessary to write down these aldoses
formulas. They are represented at the scheme (question 66).
Epimers are certain cases of dia-stereomers and, according to definition, should differ at only one asymmetric carbon atom configuration. Analyzing D-glucose and D-mannose formulas we conclude that at the third carbon atom at both molecules hydrogen atom is located at the right and hydroxyl group is located at the left; at the fourth and the fifth carbon atoms at both molecules hydrogen atom is located at the left and hydroxyl group is located at the right; thus, configurations at the third, fourth and fifth asymmetric carbon atoms at D-glucose and D-mannose are the same.
Configuration at the second carbon atom differs (at D-glucose molecule OH group is located at the right in relation to carbon chain and at D-mannose formula it is located at the left). Thus, D-glucose and D-mannose differ from each other in only one asymmetric carbon atom configuration and, thus, they are epimers.
Question 70. What is the mechanism of mono-saccharide cyclic form formation?
Answer. Mono-saccharide cyclic forms are formed at intra-molecular interaction between carboxylic and hydroxyl groups. These forms are thermo-dynamically more stable than open forms at carbohydrate molecules. Usually five-membered (furanose) and six-membered (pyranose) cycles appear. At space aldehyde (or ketone) groups and hydroxyl group at the fourth or fifth position (for aldoses) or fifth and sixth position (for ketoses) are close to each other. Due to their interaction there is cycle closing at mono-saccharide molecules.
Six-membered pyranose cycle is formed at interaction between aldehyde group and fifth atom at aldopentoses or aldohexoses; and also at interaction between keto-group with the sixth atom at keto-hexoses.
Five-membered furanose cycle is formed at interaction between aldehyde group and the fourth atom at aldotetroses, aldopentoses and aldohexoses; and also at interaction between keto-group and fifth atom at ketopentoses and ketohexoses.
As a result of cycle formation at aldohexose molecule at the first carbon atom instead of aldehyde group there is hydroxyl group (at ketoses at the second carbon atom). This hydroxyl group is called glycoside (hemi-acetal) hydroxyl group (glycoside hydroxyl). At the name of cyclic forms ending “pyranose” is added to six-membered cycles or “furanose” is added to five-membered cycles.
In mono-saccharide cyclic molecule, number of asymmetric carbon atoms increases as carbon atom being at aldehyde group or keto-group turns to be asymmetric too. In the case of galactose this is the first carbon atom, at fructose it is the second carbon atom. This carbon atom is called anomer carbon atom. Additional asymmetric carbon atom appearance leads to the increase in two times in number of optical isomers, corresponding to cyclic form in comparison to open form. Thus, for aldohexose this number is not 16 but 32 isomers. Each isomer with open form correlates to two isomers at cyclic form (anomers).
At α-anomer, anomer centre configuration is the same as asymmetric carbon atom configuration defining carbohydrate belonging to D- or L-series, and at β-anomer it is opposed. At Fischer’s projections at mono-saccharides belonging to D-series at α-anomer glycoside hydroxyl is at the right and at β-anomer it is located at the left in relation to carbon chain; situation is opposite for L-isomers, at α-anomer glycoside hydroxyl is at the left and at β-anomer it is located at the right in relation to carbon chain. Anomers are dia-stereomers and differ from each other in their properties (for example, on melting temperatures). Anomers are narrow cases of epimers.
Question 71. Write down mono-saccharide cyclic forms as Haworth’s perspective formulas.
Answer. According to Haworth cycles are drawn as plane pentagons or hexagons which are located perpendicular to drawing plane, that is why lines corresponding to front part of the ring are thick. Oxygen atom is at pyranose cycle in the farther right angle, at furanose cycle oxygen atom is at farther right angle or in the middle of back cycle part of the ring. Hydroxyl groups and hydrogen atoms are located perpendicular to cycle plane. Symbols of carbon atoms are not usually written in the cycles.
T
o
write down Haworth’s formula it is necessary to write Fischer’s
formula first and rotate it on 90о
to the right (clockwise):
I
t
is necessary to rotate carbon atom attached to hydroxyl group on 90о,
this hydroxyl group takes part at cyclization reaction. At
manno-furanose formation this is the fourth carbon atom, at
manno-pyranose formation it is the fifth carbon atom. As a result of
this rotation –OH group should be on one line with main carbon
chain. That is why, for D-isomer –СН2ОН
group is at the top and for L-isomer it is located at the bottom:
After that chain is closed and Haworth’s projection is received:
In the name of the cyclic form we should mark: anomer type ( or ), after that we mark belonging to stereo-chemical series: D- or L-; after that mono-saccharide name, which derivative this cyclic form is, but it should be without ending “-se”, in other words we should preserve gluco-, manno, fructo- etc., finally we mark cyclic form type (pyranose or furanose).
At D-series of aldohexoses in pyranose form (and at D-series of aldopentoses and ketohexoses in furanose form) СН2ОН group is always located above cycle plane which is the formal sign of D-series. For L-series this group is located under cycle plane. Glycoside group –ОН at -anomers for D-series aldoses is under the plane and for -anomers it is above cycle plane. For L-series glycoside hydroxyl at -anomers it is located above the plane and for -anomers it is located below cycle plane.
According to these rules we can write Haworth’s formulas for ketoses at furanose and pyranose forms, for example, for fructose:
D-fructose transformed
projection
Question 72. What are predominant forms (open or cyclic) of mono-saccharides in solid state and in the solution?
Answer. At solid position mono-saccharides are in cyclic form (mainly pyranose). At solutions there is balance between open form and two pairs of cyclic anomers (cyclic-oxo-tautomeric balance or cyclic-chain tautomerism). Different molecule forms which are balanced are called tautomers. In tautomer mixtures pyranose form predominates. Open forms and furanose cycles are in small amounts. - or -anomer dominance depends on monose nature, solvent, concentration and other external conditions.
Carbohydrate tautomeric forms could transform in to one another which leads to some form increasing due to its utilization at some process. Balance between all forms is dynamic. If, for example, glucose anomer is dissolved in water, it gradually transforms in to another anomer, until balanced mixture containing two anomers is formed, this mixture contains small amount of open form. This transition is accompanied by change in solution optical rotation, as each tautomer is characterized by its own plane-polarized rotation angle of plane-polarized light. This phenomenon is called mono-saccharide mutarotation.
Question 73. Write -furanose and -pyranose forms of L-arabinose. Draw their anomers in Fischer’s projections.
Answer. It is necessary to take D-arabinose as initial compound. Let’s write its formula and draw its enantiomer formula (question 6).
L-arabinose is aldopentose. Its furanose form is formed due to interaction between aldehyde group and hydroxyl group at the fourth carbon atom; and its pyranose form is formed due to interaction between aldehyde group and hydroxyl at the fifth carbon atom. At cyclization process hydrogen from hydroxyl group (С5 or С4) is added to oxygen from aldehyde group due to -bond С–О breaking, forming hemi-acetal or glycoside hydroxyl (which is in the frame). Oxygen from hydroxyl group at С4 or С5 after hydrogen elimination is attached to carbon at aldehyde group at С1. There is oxygen bridge formed between С1–С4 and it locks five-membered cycle, or С1–С5 and it locks six-membered cycle.
О
О НО Н Н
ОН
С
– Н 1С
– Н C
С
Н
О
Н Н 2
ОН H
ОН H
ОН
Н ОН НО 3 Н HO Н HO Н
Н ОН НО 4 Н О Н О Н
СН2ОН 5СН2ОН СН2ОН СН2ОН
D-arabinose L-arabinose -L-arabino-furanose -L-arabino-furanose
О
О НО Н Н
ОН
С
– Н 1С
– Н C
С
Н О Н Н 2 ОН H ОН H ОН
Н ОН НО 3 Н HO Н HO Н
Н ОН НО 4 Н НО Н НО Н
СН2ОН
5СН2ОН
О СН2
О СН2
D-arabinose L-arabinose -L-arabino-pyranose -L-arabinopyranose
At hemi-acetal form the first carbon atom is transformed into asymmetric carbon atom. As a result, at cycle closing from one open aldehyde form (oxo-form) there are two cyclic hemi-acetal forms appearance which differ from each other by the position of hemi-acetal hydroxyl.
Cyclic form with hemi-acetal hydroxyl located at one side (at cis- position) with hydroxyl defining monose configuration (belonging to D- or L-series) is called -form. Cyclic form at which hemi-acetal hydroxyl is at trans- position with hydroxyl defining configuration is called -form. - and -forms are dia-stereomers and they are called anomers.