Carbohydrates

Fisher projections

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Conditioning and redistribution of glycoproteins by Golgi complex

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Pentoses and hexoses cyclise to form furanose and pyranose rings.

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Maltose

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Glycoproteins

1 to 20% carb, 99 to 80% protein. Carbohydrates are usally short, often branched oligosaccharides, covalently attached to protein backbone. e.g. plasma, mucus, blood proteins. Cell adhesion Blood serum proteins Asn link recognition on the protein - Asn - X - Ser - Asparagine link / Serine threonine link

Classification of polysaccharides

1. Homopolysaccharides a. Storage homopoly. b. Structural homopoly. (for every 10 alpha-1,4-glycosidic bond, approximately 1 alpha-1,6 glycosidic bond) 2. Heteropolysaccharides a. Glycosaminoglycans b. Glycoproteins

Oligosaccharide composition of glycoproteins

3 Mannoses 2 Acetylglucosamines - form a core for variety of glycoproteins.

Oligosaccharides

Contain between 3 and 10 monosacch. units, which may be the same or a mixture of different monosacch.

Aldose sugars

All aldose sugars are derived from either the parent D- or L- form of glyceraldehyde by the addition of extra H-C-OH groups whilst retaining the aldehyde (CHO) group at the top and the hydroxymethyl (CH2OH) group at the bottom of the molecule. There are two series. i.e. D- and L- of aldose sugars, irrespective of the number of the carbon atoms present. The general rule for calculating the number of isomers for monosaccharides containing a defined number of carbon atoms is: Determine the # of asymmetric C atoms - N The # of isomers 2^N

Glycosaminoglycans

Always repeating sequence of 2 monosaccharides, one of which is an amino sugar. Most associate (noncovalent) with protein (85% carbohydrate, 15% protein, forming Proteoglycans (form extracellular matrix of cartilage - brushes) Osteoarthritis occurs when proteoglycan looses its aggrecan brushes. Mucopolysaccharides: Although precise clinical features vary with disease, all mucopolysaccharides result in skeletal deformities and reduced life expectancies.

Monosaccharides

Basic units of carbs. Glucose / Fructose / Galactose / Ribose

Amylopectin

Branched glucose homopolymer, containing both alpha-1,4-glycosidic bond and 1,6. The branch points are every 6-8 glucose residues. Its moderate solubility is due to one reducing C-1 end, and many non-reducing C-4 ends.

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Carbohydrates are molecules possessing the empirical chemical formula [CH2O]n (hydrated carbon). They are either: Polyhydroxy Aldehydes (Aldose sugar) (-CHO) i.e. the chemical functional groups present are aldehyde and alcohol . . . . . Polyhydroxy Ketones (-C=O) Ketose sugars. i.e. the chemical functional groups present are ketones and alcohol.

Pyranose and furanose rings are not planar

Chair form . . . . . . Boat form . . . . .

Disaccharides

Composed of two monosaccharide sugar units, which may be the same or two different monosacch. Maltose = 2(glucose) Sucrose = glucose + fructose Lactose = glucose + galactose

Amylose

Comprises 20% of starch and is a straight chained alpha-1,4-glucose polymer. (i.e. amylose contains maltose disaccharide units and is unbranched. The alpha-1,4-glycosidic bond imposes a slightly spiral shape on the molecule compared to perfectly linear cellulose.

Storage polysaccharides

Contain alpha-glycosidic linkages which produce helical polymers that are open structures accessible to bulk water.

Diseases associated with abnormal carb metabolism

Diabetes Mellitus Galactosaemia Fructose intolerance Lactose intolerance

Definitions

Epimers - differ at 1 position (1 different -OH/H group) Enantonimer - mirror image Diastereoisomers - not mirror image

Enzymes of oligosaccharide assembly:

Glycosiltransferases. Define ABO blood groups.

Polysaccharides

High molecular weight carbohydrate polymers, defined as containing 11 or more monosaccharide units. Important biological polysacch. contain many hundreds of monosaccharide units. A polysaccharide may be linear. (e.g. Cellulose) or branched (Glycogen / Starch) Homopolysaccharides - contain only on type of monosaccharide unit - Cellulose, Glycogen, Starch Heteropolysaccharides - contain different types of monosacch. Heperin, Mucins, Glycoproteins, Hyaluronic acid.

Errors in glycosilation can result in pathological conditions

I-cell disease (mucolipidosis II) Lysosomes accumulate large amounts of glycosaminoglycans. No enzymes to digest, in spite of their abundance in blood. This is due to incorrect addressing. Normal enzymes contain mannose-6-phosphate. In I-cell patients, the phosphotransferase catalysing mannose enzyme is missing, hence the enzyme cannot be delivered to lysosome.

Starch

Is the storage carbohydrate and energy reserve of plants. The bulk of human carbohydrate is taken as this polysaccharide. Polymeric starch has a much lower osmotic pressure than a solution of glucose of corresponding concentration. Starch is composed of two structurally distinct glucopolysaccharides: 1. water soluble amylose (20%) 2. moderately soluble amylopectin. (80%)

Glycogen

Is the storage carbohydrate of animals, corresponding to starch in animals, In humans, the liver contains 8% by weight of glycogen and in muscle 1%. Glycogen is a single structure, not a mixture of two as in starch, being very similar to amylopectin, but even more highly branched. Glycogen is moderately soluble, forming colloidal solutions. Enzymes and other proteins are associated with glycogen granules. Glycogen is a readily mobilised storage form of glucose. It is very large, branched polymer of glucose residues. Most of the glucose residues in glycogen are linked by alpha-1,4 glycosidic bonds. Branches are created by alpha-1,6 glycosidic bonds. The branches in glycogen tend to be shorter than in amylopectin.

Hetero-polysaccharides

Largest and most complex group of carbohydrates containing an astronomical variety of structures.

Reactions with alcohol Glucose + alcohol = methanol

Methyl-alpha-D-Glucopyranoside . . . . . . Methyl-beta-D-Glucopyranoside . . . . . .

Biomedical importance 2

Most other carbohydrates present in the body can be derived from glucose. Ribose / Deoxyribose - RNA / DNA Lactose - Milk Glycogen - Stored in the liver and muscles. Glucose is a major fuel for all tissues, and the sole fuel molecule in the Brain and erythrocytes.

Reactions with amines to form glucosamines

N-Glycosidic bond . . . . . . Glucose but not glucoseamine can be readily oxidised, while: Glucosamine is nonreducing sugar. Glucose binds to haemoglobin - diabetes mellitus test, measuing glycosylated haemoglobin.

Glucose composition

Open chain form <1% alpha-D- Glucopyranose app. 36% beta-D- Glucopyranose app. 64% . . . . . . . . . (alpha - OH is down / beta -OH is up)

Monosaccharides 2

Simple monosaccharides are polyhydroxy aldehydes and ketones. They react chemically as both alcohols and either aldehydes or ketones. More complex monosacch. have additional chemical functional groups. The most common of these groups are (COOH/COO- and (NH2/NH3+). Monosacch. sugars contain a minimum of 3 carbon atoms and no maximum. However, the important biological monosaccharides contain 3 to 6 carbon atoms (trioses / tetroses pentoses / hexoses) (5 & 6 most common) They contain multiple asymmetric carbons. Naturally occurring hexoses tend to be D-isomers. (D-glucose/fructose) Dexter - On the right / right handed Laevo - On the left / left handed . . . . . .

Structural polysaccharides

Structural polysaccharides contain beta glycosidic linkages which produce linear polymers, suitable for forming fibres. Cellulose The most abundant organic compound in the world, comprising more than 50% of all carbon found in vegetation. It is a linear polymer of glucose monomers joined by beta-1,4-glycosidic bonds. The beta-1,4-glycosidic linkage imposes a perfectly linear shape on cellulose permitting stacking of multiple layers of polymer. This stacking renders cellulose water insoluble, because the hydrophilic -OH groups become involved in inter chain H-bonding, and are rendered inaccessible to solvation by external water. Cellulose therefore constitutes essential roughage in the diet.

Enzymes: sucrase / lactase and maltase are located on the surface of the epithelium cells of the small intestine.

Sucrose - nonreducing sucrase Lactose - reducing lactase Maltase - reducing maltase

Chitin

The exoskeleton of insects, crustaceans and fungi contain chitin. Chitin is composed of N-acetylglucosamine residues in beta-1,4-glycosidic linkages. Chitin forms long straight chains ideal as structural elements. Chitosan is deacetylated chitin. It is a blood clotting agent - bandages / surgical thread. The body can't break Chitin down, therefore it is ideal for weight loss.

Biomedical importance 1

The typical example of an important human carbohydrate is Glucose. Although free glucose is not the most abundant carbohydrate ingested, as a result of digestion, it is the most abundant molecule absorbed in the blood stream. The bulk carbohydrate ingested is Starch, a polymer of glucose. (bread,potatoes,pasta rice)

Phosphorylated sugars are key intermediates in energy generation and biosynthesis

They cannot cross the membrane because of the negative charge. Phosphorylation makes them more reactive in important metabolic pathways.

Disaccharides 2

Two glucose units can be joined together by a glycosidic bond between hydroxyl groups on carbons 2,3,4 and 6. The alpha- or beta- anomeric C-1 hydroxyl. Thus there are eight isomers of glucosyl glucose.

Glucose

Water soluble Can contain an amino group, usually on C2. e.g. glucosamine; A hydroxyl can be replaced by -H to give deoxysugars e.g. fucose (6-deoxygalactose) Deoxyribose (C-5 sugar) Contains OH groups Reacts as alcohols giving organic esters with acids. Reacts as phosphates and sulphates with phosphoric and sulphuric acid. Contains an aldehyde group which can be either oxidised or reduced.

Heparin

is secreted by mast cells lining the wall of blood vessels, the liver and lung. It is also present in basophilic granules. Heparin is an anti-coagulant, that functions by binding to an inhibiting the blood clotting factor antithrombin. Heparin-antithrombin complexes sequester thrombin, retarding clot formation.

Erythropoeitin (EPO)

stimulates erythrocyte production 40% of carbohydrate in EPO enhance its stability.

Glycosilation

takes place in the lumen of the ER (-O and -N linked) and the Golgi complex (only -O linked) N-glycosilation involves activation of oligosaccharide by binding dolichol phosphate.

Lectins

universal carbohydrate recognition proteins.