Carbohydrates

Anna Drew

with grateful acknowledgement for inspirational teaching received at

The School of Pharmacy, University of London

• Uses– green plants

• store energy as CHO – eg starch

• structural material (form large proportion of plant biomass)

– eg cellulose

• Structures– mono = 1 unit– di = 2 units (useful in pharmacy)– oligo = 2-8 units– poly = N units

• Type sugar varies enormously

• Formation– sugars are formed as a result of

photosynthesis• glucose-6-phosphate and fructose-6-phosphate

– hydrolysed to glucose or fructose and converted to starch or consumed as energy

– form sugar nucleotides with UTP or ATP -> uridine diphosphoglucose etc and converted to different sugars

– sugars unite with a wide variety of compounds to form glycosides

Monosaccharides

• 3-9 carbon atom sugars– (pentoses 5, hexoses 6 most common in plants)

• have to be obtained by chemical reactions• only a few are free in plant

– many as polysaccharides

[A] Dextrose (glucose)

• dextrose-α-D-glucopyranose (pyranose form)– produced by hydrolysis of starch-HCl under heat pressure (45lb

per sq in for 30min)– don’t want a mixture eg with maltose in

• Uses:– nutrient replenishment PO or IV

» dextrose injection» dextrose + saline (NaCl) injection» dextrose + sodium citrate injection» other forms

[B] Glucuronic acid• 6C: Ch2OH -> acid (glucuronic or gluconic)

– from oxidation of glucose

• Uses:– as calcium or ferrous salts

» calcium glucuronate for osteoporosis (loss of calcium from skeleton etc)

» ferrous gluconate for anaemias (gluconate form less irritant to GI tract and better absorbed than other salts)

[C] Liquid glucose• Mixture of dextrose, maltose or dextrins

– from incomplete hydrolysis of starch » (less pressure 30lb per sq in)

• Uses:– as sweetners, substitutes for sucrose in syrups

[D] Fructose• Occurs in fruits

– obtained from hydrolysis of sucrose

• Uses:– as sweetner in diabetic foods instead of glucose (not a

problem since it is not easily metabolised)

DisaccharidesCondensation of 2 monosaccharide molecules

Two main ones:

[1] Sucrose

= α-D-glycopyranosyl-β-D-fructofuranose= glucose + fructose

Main sources:

• Sugar cane Saccharum officinarium

– crushed, boiled in lime, coagulated protein removed by filtration, decolourised, then crystallised (remainder in cattle food)

– Used as a sweetening agent

• Sugar beet Beta vulgaris

– sliced and boiled in hot water, then as above

– Uses:» cherry/raspberry juice as a masker» esters – many OH and ethanolic groups can be added to

form esters easily – used as emulsifiers and wetting agents or dispersants, lotions, gels – non-irritant so can be used internally

[2] Lactose

= galactose + glucose

Source:• does occur in plants but normally obtained from cows milk

(commercial by-product of cheese)

Used as:• tablet diluent esp in antibiotic preparations• nutrient in infant foods• less sweet than sucrose

Polyols

• Sugar alcohols– occur naturally – produced from reduction of unit sugars

• (removal of aldehyde or keto group)

– Sorbitol (D-glucitol)• From sorbose in

– Sorbus aucuparia (mountain ash red berries)– many rosaceous fruits– seaweeds

– Mannitol• From mannose in

– Travinus ornus (damaged stems)– seaweeds (main commerical source)

• Uses:

– both used as alcohols– less sticky to deal with in biochemistry

– Mannitol:• limited uses• diagnostic reagent in kidney tests

– not metabolised

• diluent• diabetic foods

– Not as sweet as sucrose or glucose

– Sorbitol• diabetic foods• with sucrose to stop crystallisation of sucrose

– eg in toothpastes, cosmetic creams

Polysaccharides

• Condensation of sugar phosphates and sugar nucleotides

• Polyuridines (acid sugars) occur in polymers

• Building blocks:

Hexoses: • D-glucose, D-mannose, D-fructose, D-galactose

Pentoses: • D-xylose, L-arabinose

Modified sugars: • D-glucosamine, D-glucuronic acid, D-galacturonic acid. D-

mannuronic acid, L-fructose, L-rhamnose

• Starch: essentially a storage form of sugars [α 1-4 links]• Cellulose: building material of the plant [β 1-4 links]

• glycosidic bonds initiated at the C1 anomeric centre:

• sugars and polysaccharides normally an orderly arrangement of two components

• not all are straight chain polymers

Amylose – mol wt 103–104

Amylopectin – mol wt 107

– formed in leaves– can be reconverted to translocating form (“transitional starch”) to

go to other parts of the plant

STARCH

Source:• found mainly in seeds, fruit, tubers• exception is the stem of the sago palm• good commercial sources

– potato, maize, wheat, rice, oat, barley– tapioca or cassava in tropics– arrowroot, banana, buckwheat, sago palm stem

– Amylose• unstable – H-bonding between molecules hydrolyses in

dilute solution• easily precipitated – can never get it back

– Amylopectin• major constituent of starch• forms very viscous solutions• stable in water, good in pastes

• use of amylose or amylopectin depends on requirements• if want greater % amylose choose certain hybrids

Evans WC. Trease & Evans’ Pharmacognosy. 14th Edition. London: WB

Saunders, 1996

Starch hydrolysis

i) phosphorylase– found in plants– hydrolyses amylose -> glucose-I-phosphase– which attacks outer chains of amylopectin– can’t reach or breakdown α1,6 links in molecule

ii) amylase– hydrolyses straight chains links but not α1,6– amylose -> glucose + maltose + multitriose molecules– can work on β-amylose

iii) α-glucosidases– α1,4 links hydrolysed not α1,6– commerical fungal enzymes needed to hydrolyse α1,6 linkages

Commercial preparation of starch

• Sources: maize, rice, potato

MAIZE (Zea mays)

– starch is found in the endosperm– embryos also useful

Pericarp testa

Embryo (germ)

Endosperm (grain)

– soak in water + 0.2% sulphurous acid (SO2) at 50oC for 2 days to remove pericarp (testa)

– roll to split, partially crush and separate embryo + endosperm

• embryo contains oil so floats and is skimmed off– wash endosperm with water– liquor passed over series of shaking-sieves,

concentrated by sedimentation and deposited over tables with troughs ‘tabling’

• each repetition reduces protein level– [Nowadays: repeated centrifugation used to collect

starch sediment]– undergoes drying process

Embryos:• pressed to yield maize oil

– contains vitamin E– germ seed cake fed to cattle

RICE (Oryza sativa)

– grains softened by soaking in 0.5% caustic soda (NaOH)

• loosens and partially dissolves glutinous matter holding starch granules together

– ground in stone mill -> milky fluid (starch suspension)– diluted and allowed to settle in vats ie concentrated by

sedimentation– drained over cloth lined boxes– (or centrifuged to remove starch)– undergoes drying process

POTATO (Solanum tuberosum)

– contain 16-25% starch• easier to separate it than via cereals

– skin removed• contains enzymes that discolour starch

– ‘rasped’ to a pulp in teeth-lined drums• tears open most cells

– starch separated by shaking-sieves, residue ground between millstones, repeat

– liquid centrifuged– concentrated starch mixed with water and further

purified by sedimentation in vats– dried to reduce <20% moisture

[1] Starch - absorbent properties• dusting powder• ointments (“mucilage of starch”)• disintegrating agent in tableting

[2] Other starch products• starch doesn’t dissolve in cold water• isn’t readily adsorbed• hence it is slightly altered

Uses

i) Formalised starch– treated with formaldehyde– removes swelling properties in water– can be adsorbed by body - used in surgeons gloves (can be

sterilised)– Uses - lubricant properties – many uses in food industry (gels,

pastes)

ii) Soluble starch– (a) from potato

» mixed with ethanol and acid at 10mmHg» neutralised with NaCO3

» washed with ethanol» grains still look same» in cool water get an opaque solution

– (b) from maize» same treatment» or put through rollers to get same effect» or use chlorination process to get a gel form

– Used in tableting as soluble

[3] Commercial dextrins and dextrans

a) Dextrins• prepared by acid and heat -> white dextrin• or just heat (roasting starch) -> yellow dextrin• white has less adhesive properties

– smaller molecule since partly broken down by acid• Main use:

– adhesive dressings– food products (binding – pastes, thickeners)

b) Dextrans• not starch• polymer of 1,6 links of glucose units• formed by many microorganisms• commercially used Leuconostic mesenteroides converts sucrose ->

α 1,6 glucose dextrans• Used

– as blood plasma expanders (severe haemorrhage, bad burns)» separated by molecular weight» low molecular weight dextran used if faster excretion required

– as adhesives and cosmetic powders (stick to moist skin)

INULIN

• fructose polymer• stored in some plants as an alternative food

reserve to starch– chicory (Cichorium intybus)– dandelion (Taraxacum officinale)

• mammalian enzymes can’t break it down• readily excreted in urine• Used

– to determine GFR (glomerular filtration rate)– sweetening agent

CELLULOSE

Cell walls:– cellulose + pectin hemicellulose + derived

sugar molecules (+ lignin -> 2y thickening)– pectin most useful

Proposed model of a primary plant cell wall

• Cellulose = straight chain glucose polymer

– has β 1,4 links (1,4-β-D-glucopyranosyl units) but cannot form a helix

– > different properties with strength• used as building block rather than energy store

– large part of molecule cellulose– fibres parallel held by H-bonds and Van der Waals

forces– some parts of molecule are crystalised

• amorphous regions of molecule hydrolysed more easily

Commercial preparation

Source: cotton

– 98% cellulose– remove impurities, pectin proteins

• de-wax with solvents

• boiled in O2 free alkali to get pure cellulose

– microorganisms or strong acid +heat needed to break down cellulose

• cellulose -> cellobiose (dimer) -> glucose I

[cellulase]

I

[cellobiase]

Uses

• Dressings– good absorption– won’t dissolve in most solvents– some swelling with moisture– dissolved with freshly prepared CuOxam

• Filtration and chromatological medium

• Tableting– partially hydrolyse microfibrils to get certain properties– or use a little or in combination– makes tablets hard but can be used in tablet coating

Cellulose derivatives

• -OH groups replaced

• Cellulose acetate• acetate replaces approx 2.3-3 –OH groups per

molecule• 25% cellulose acetate: 75% cellulose phthalate

combination used for tablet coatings

• Methylcellulose• product produces viscous suspensions• good emulsifier

– Vegetable and mineral oils, barrier creams, bulk laxatives, tablet binder

• Hydroxycellulose• Carboxycellulose

• used as thickeners and stabilisers for p’ceutical and dairy products (viscous solutions)

• also creams and tablet coatings sometimes

• Oxidised cellulose• 20% -OH groups converted using HNO2 acid• haemostatic properties

– gauze linen dressings, in lint

• Cellulose nitrate• nitration of polymer - guncotton• collodion (solution produced by dissolving in ether

or organic solvents) used as skin coatings over abrasions (wound dressing, topical med. carrier)

PECTIN

• Mol wt 104-105

– hydroxy groups oxidized then methylated– from galactose– methylation not always complete

• Useful high mol wt polymer:– tends to coagulate with Cu and Al ions in aqueous -> viscous

solutions, gels– diarrhoea preparations eg kaopectate– haemostatic – substitute for plasma therapy in shock

• Source: best from fruit eg apple, pear

GUMS

• Mixtures of following give different physical properties:– galactose, mannose, xylose, arabinose, rhamnose,

fucose (an aldose/hexose deoxy sugar C6H12O5)

• 3 types:

– exudate gums– seed gums– seaweed gums

[A] Exudate gums

[1] Acacia

• From: Acacia senegal (Leguminosae)• grows in Sudan, Central and West Africa• trees grow in semi-arid conditions• produce gummy exudate to repair damage

– by animal, insect or man

• when 6 years old• tapped to collect acacia gum• comes in round balls ‘tiers’

– sorted by size and colour– darker if phenol present– should be clear or glassy

• has no odour or taste in aqueous solution– 1-6, 1-3 links containing L-arabinose, L-rhamnose and

mainly D-galactose + D-glucose (glucuronic acid)– galactose 3: arabinose 3: glucuronic acid 1: rhamnose 1– soluble in water, makes low viscosity solutions– easily digested and absorbed– non-toxic

• Uses:– stabiliser in emulsions– cough, diarrhoea, throat preparations (demulcent

properties)

• expensive but the best

[2] Tragacanth

• From: Astragalus gummifer and other species (Leguminosae)

– thorny shrub growing at 1000-3000m– in Anatolia, Syria, Iraq, Iran, former USSR– produced immediately from pith and cortex breakdown in

damaged bark– stringy, contains starch

• polymer more acidic than acacia• main acid is D-galacturonic acid (43%)• Constituents:

– tragacanthin (acid groups, water-soluble) 1:– bassorin (no acid groups, water-insoluble fraction) 2– both insoluble in alcohol

• best grades contain least tragacanthin– but where it is at a high level found to contain:– galacturonic acid (43%), xylose (40%), L-fucose (10%),

D-galactose (4%)

• separated by precipitation less easily than acacia• forms a translucent solution since insoluble

• Uses: suspending agent, thickening agent, tableting

[3] Sterculia

• From: Sterculia urens– Karaya gum, Indian/Bassora tragacanth– India, Pakistan, Africa

• previously thought an inferior substitute for tragacanth

• similar but D-galacturonic acid linked to rhamnose• contains no starch (stains pink w ruthenium red)

• Uses:– granular grade – bulk laxative– powdered grade – lozenges, pastes, denture fixative

powders, stoma adhesive

[B] Seed gums

[1] Psyllium seed (flea seed)

• From: – Plantago afra, P.indica: French/Spanish psyllium– P.ovata: blonde psyllium, ispaghula, Indian plantage

seed– epidermis of the testa

• Neutral polymer (mucilage) from the seed coat– ground to produce powder– not purified– D-galacturonic acid + L-arabinose, D-xylose and L-

rhamnose

• Uses:– demulcent– chronic constipation (ispaghula husk SF 40-90)

[2] Locust bean, carob gum

• From: Ceratonia siliqua (Leguminosae)– endosperm separated from seeds– Cyprus, Egypt, Mediterranean

• Major units mannose and galactose– branches shorter and less branched – gives advantages– neutral

• Uses:– as for tragacanth– food industry – thickener in place of starch– not such a good suspending agent (contains an enzyme)

[3] Guar gum

• From: Cyamopsis tetragonobulus– ground endosperms– Indian leguminous plant

• Main constituent: galactomannan

• Uses:– food industry – 5-6x thickening power of starch– ? oral hypoglycaemic drug – changes in gastric emptying

and GI transit time– lowers cholesterol levels - ? binding bile salts in gut

[C] Seaweed gums

– major components of cell walls– can be extracted from

• red algae - Rhodophyceae• brown algae - Phaeophyceae

– with boiling water

[1] Alginic acid

• From: brown seaweed – Macrocystis sp., Laminaria sp.– grows in colder waters of the world– N.Atlantic Ascophyllum nodosum cut with sickles or

harvesters, rest storm-cast– processed or dried to 12-17% moisture for storage

• Extraction: Stanford method– dried milled weed macerated with dilute Na Carbonate solution

and mass diluted with soft water– insoluble matter decanted or settled out– clear liquor

» poured into dilute sulphuric acid or dilute Ca Cl2 solution» insoluble alginic acid or calcium alginate precipitate out» rolled to expel remaining liquid» OR ethyl alcohol added to precipitate out sodium alginate

• D-mannuronic acid + L-guluronic acid (20-40%) – in blocks of alternating units and blocks of single units– quite highly acidic straight chain polymer (MW 50-200,000)– contains trapped ion salts eg Ca2+ in guluronic acid kinks (‘egg

box gel’)

• Uses: -> viscous solutions, no taste or toxicity, many uses!– food, dental, rubber, textile, paint, cosmetic, p’ceutical ind’y

» suspending, thickening, stabilising, gelling with salts etc– p’ceutical: barrier creams, ointments, pastes, jellies, tablets,

gastro-oesophageal reflux products– textile: wound dressings (haemostatic)

[2] Agar

• From: red algae– Gelidium sp., Gracilaria sp.

• Extraction: Japanese coast– cultivated by placing poles in the sea to form supports

– poles withdrawn and algae stripped

– other methods of collection

» rakes and shovels from small boats, diving

– taken ashore, dried

» beaten and shaken to remove sand and shells

» Bleached by watering and sunlight (removes salt)

– boiled with acidulated water for several hours

– mucilaginous decoction filtered through linen while hot

– jelly forms on cooling, cut into bars and forced through wire to make strips

– moisture removed by freezing/thawing, drying at 35oC and powdering

• Constituents:– agarase = α-D-galacturose & 3,6 anhydro-β-L-galactose– agaropectin (40%): D-galactose, D-glucuronic acid, L-

galactose with sulphate ester groups– make a series of polymers

» at low concentration very viscous stable solutions» hence low concentrations used as solid gel

• Uses:– agar plates, chromatography– food industry – thickener, emulsifier

[3] Irish Moss• From: Chrondus crispus, Gigartina stellata

– red alga – carrageen, Chondrus

• Similar polymer to agar:

• Uses:– kappa form has stronger gelling properties, emulsifier (for cod-

liver oil and other oils), holds solid particles in solution as suspensions

– binder in toothpastes; many uses in food industry

Use of polymers• According to desired properties:

– linear, neutral• occupy large space• high degree of hydration• where low concentration is required

– precipitate out at high concentration

– branched, neutral or acidic• can use a larger concentration before they precipitate• gels, pastes etc

– side chains mean shorter molecule

– for restricted flow solution• use cellulose or carob• not pectins, carrageen, acacia, tragacanth -> smooth and viscous solutions

– carrageen holds particles in suspension