Carbohydrates

1
Carbohydrates

• Anna Drew
• with grateful acknowledgement for inspirational
  teaching received at
• The School of Pharmacy, University of London

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• 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

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• 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 -gt uridine
  diphosphoglucose etc and converted to different
  sugars
• sugars unite with a wide variety of compounds to
  form glycosides

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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-a-D-glucopyranose (pyranose form)
• produced by hydrolysis of starch-HCl under heat
  pressure (45lb per sq in for 30min)
• dont want a mixture eg with maltose in

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• Uses
• nutrient replenishment PO or IV
• dextrose injection
• dextrose saline (NaCl) injection
• dextrose sodium citrate injection
• other forms
• B Glucuronic acid
• 6C Ch2OH -gt 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)

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• 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)

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Disaccharides

• Condensation of 2 monosaccharide molecules
• Two main ones
• 1 Sucrose
• a-D-glycopyranosyl-ß-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

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• 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

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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)

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• 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

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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

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• Starch essentially a storage form of sugars a
  1-4 links
• Cellulose building material of the plant ß 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

13
STARCH

• Amylose mol wt 103104
• Amylopectin mol wt 107
• formed in leaves
• can be reconverted to translocating form
  (transitional starch) to go to other parts of
  the plant

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• 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

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Evans WC. Trease Evans Pharmacognosy. 14th
Edition. London WB Saunders, 1996
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Starch hydrolysis

• i) phosphorylase
• found in plants
• hydrolyses amylose -gt glucose-I-phosphase
• which attacks outer chains of amylopectin
• cant reach or breakdown a1,6 links in molecule
• ii) amylase
• hydrolyses straight chains links but not a1,6
• amylose -gt glucose maltose multitriose
  molecules
• can work on ß-amylose
• iii) a-glucosidases
• a1,4 links hydrolysed not a1,6
• commerical fungal enzymes needed to hydrolyse
  a1,6 linkages

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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)
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• 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

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• 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 -gt 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

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• 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 lt20 moisture

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Uses

• 1 Starch - absorbent properties
• dusting powder
• ointments (mucilage of starch)
• disintegrating agent in tableting
• 2 Other starch products
• starch doesnt dissolve in cold water
• isnt readily adsorbed
• hence it is slightly altered

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• 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

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• 3 Commercial dextrins and dextrans
• a) Dextrins
• prepared by acid and heat -gt white dextrin
• or just heat (roasting starch) -gt 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 -gt a 1,6 glucose dextrans
• Used
• as blood plasma expanders (severe haemorrhage,
  bad burns)

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• INULIN
• fructose polymer
• stored in some plants as an alternative food
  reserve to starch
• chicory (Cichorium intybus)
• dandelion (Taraxacum officinale)
• mammalian enzymes cant break it down
• readily excreted in urine
• Used
• to determine GFR (glomerular filtration rate)
• sweetening agent

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CELLULOSE

• Cell walls
• cellulose pectin hemicellulose derived sugar
  molecules ( lignin -gt 2y thickening)
• pectin most useful

Proposed model of a primary plant cell wall
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• Cellulose straight chain glucose polymer
• has ß 1,4 links (1,4-ß-D-glucopyranosyl units)
  but cannot form a helix
• gt 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

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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 -gt cellobiose (dimer) -gt glucose

I cellobiase
I cellulase
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Uses

• Dressings
• good absorption
• wont 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

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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

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• Hydroxycellulose
• Carboxycellulose
• used as thickeners and stabilisers for pceutical
  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)

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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
  -gt viscous solutions, gels
• diarrhoea preparations eg kaopectate
• haemostatic substitute for plasma therapy in
  shock
• Source best from fruit eg apple, pear

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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

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• 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

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• 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

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• 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

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• 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

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• 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

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• 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)

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• 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)

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• 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

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• 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

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• 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 -gt viscous solutions, no taste or toxicity,
  many uses!
• food, dental, rubber, textile, paint, cosmetic,
  pceutical indy
• suspending, thickening, stabilising, gelling with
  salts etc
• pceutical barrier creams, ointments, pastes,
  jellies, tablets, gastro-oesophageal reflux
  products
• textile wound dressings (haemostatic)

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• 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

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• Constituents
• agarase a-D-galacturose 3,6
  anhydro-ß-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

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• 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

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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 -gt
  smooth and viscous solutions
• carrageen holds particles in suspension