Carbohydrate Derivatives: Comprehensive Overview

Derivative of Carbohydrates

• Monosaccharides undergo reactions to form carbohydrate derivatives.
• Monosaccharides have hydroxyl groups where substituents attach or are replaced by other functional groups.
• Examples include:
  • Amino sugars
  • Acidic sugars
  • Sugar alcohols
  • Sugar phosphates
• Sugar derivatives occur naturally and have important biological functions.
• Once formed, the transformed sugar molecules resemble the sugars and the added substituent but functions and characteristics change and it is not considered a sugar anymore.
• Sugar alcohols taste sweet but are not completely absorbed by the human body, so they provide fewer calories and are widely used as health-oriented food.

Amine Sugars

• Monosaccharides where one or more hydroxyl groups are replaced by an amino group.
• The amino group can be free or derivative.
• More than 60 amino sugars are known.

Common Examples:

Glucosamine

• Also known as 2-amino-2-deoxy-D-glucose ($C<em>6H</em>{13}NO_5$).
• An aminosugar derived from glucose, produced in the body from glucose and glutamine.
• Enzyme glucosamine synthetase facilitates the reaction:
  $Glucose + Glutamine \longrightarrow Glucosamine$
• The -OH group at the C2 position in glucose is replaced by an amino group -NH2.

Occurence:

1. Naturally found in bones, bone marrow, shells of shellfish, animal cartilage, and fungi.
2. Produced by chondrocytes in cartilage in human beings.
3. Commercial preparation is mostly derived from chitin present on the outer covering of shellfish.

Preparation Available in 3 Forms:

• Glucosamine sulfate
• Glucosamine hydrochloride
• N-acetyl glucosamine

Biological Functions:

1. Used as a precursor in the biochemical synthesis of glycosylated proteins and lipids.
2. Maintenance of healthy joint tissue:
   • Glucosamine stimulates synthesis of proteoglycans, glucosaminoglycans (mucopolysaccharides), and collagen.
   • Plays a role in the formation of cartilage and cushioning synovial fluid between the joints.
   • Classified as a chondroprotective agent.
3. Formation and maintenance of body tissue:
   • Glucosamine helps in the formation of nails, skin, eyes, bones, ligaments, tendons, and the digestive and urinary systems.
4. Supplementary glucosamine can be an important source of this vital amino sugar for those with reduced capacity to produce it, such as the elderly. Clinical studies prove it is more effective than ibuprofen in treating osteoporosis.
5. Glucosamine improves the functioning of the digestive system and provides relief in inflammatory bowel disease.
6. Glucosamine acts as an immune modulator with antitumor and antiviral properties and also shows some activity against HIV.
7. It has the ability to reduce the progression of experimental cancer. Reduced glucosamine levels are found in people with colon cancer.
8. Potential antioxidant effects: Glucosamine may exhibit antioxidant properties, helping to neutralize free radicals and reduce oxidative stress in cells.
9. Synergistic effects with other nutrients: It works synergistically with other nutrients such as omega-3-fatty acids to enhance anti-inflammatory effects.
   • It is used in cosmetic formulations for its potential to improve skin hydration and elasticity, as well as to promote wound healing.

Side Effects and Precautions:

• High dosages may lead to gastric problems, indigestion, and heartburn; hence, it should be taken under medical supervision.

N-acetyl Glucosamine

• A monosaccharide derivative of glucose.
• Chemically, it is an amide between glucosamine and acetic acid and is significant in several biological systems.

Occurence:

1. In animals as outer shells of shellfish, bacterial cell wall-peptidoglycan, fungal cell wall-chitin, extracellular matrix of animal cells.
2. In human beings, the skin cartilage and blood vessels as a component of hyaluronic acid & in bone tissue, cornea & aorta as a component of keratin sulfate.

Biological Functions:

1. Formation of cell wall:
   • It is a part of a biopolymer in the bacterial cell wall built from N-acetyl muramic acid cross-linked with oligopeptides at the lactic acid residue of N-acetyl muramic acid.
   • This layered structure is called peptidoglycans.
   • Glc. NAc. is the monomeric unit of the polymer of chitin which forms the outer covering of insects and crustaceans.
2. Role in Neurological health:
   • N-acetyl glucosamine is also of note in neurotransmission, where it is thought to be an atypical neurotransmitter functioning in nociceptive (pain) pathway.
3. N-acetyl glucosamine helps in immune system functioning particularly in HIV and tumors.

Treatment of autoimmune disease

• N-acetyl glucosamine decreases pain and inflammation, increases range of motion in osteoarthritis patients, and helps repair cartilage

Treatment of inflammatory bowel disease

• N-acetyl glucosamine has been linked to Crohn's disease, interstitial cysts and ulcerative colitis. Deficiencies of N-acetyl glucosamine has been linked to diseases of bowels and bladder. Those with colon cancer show particular deficiencies.

Formation of hyaluronic acid

• Glc. NAc. on polymerization with glucuronic acid forms hyaluronic acid which is required for the proper functioning of human body.
• It is important neurotransmitter.
• Glucosamine has been shown to repair the gut lining defensive barriers called the glycosaminoglycan (GAG).
• It helps to prevent flu-virus and herpes-virus in animals.

Skin lightening

• According to study published in "Journal of cosmetic dermatology", N-acetyl glucosamine helps in skin lightening and hence is used in skincare products.
• It helps in blocking production of melanin.
• It helps in reducing hyper pigmentation caused by ageing and sun exposure.
• It decreases insulin secretion and limits the cholesterol level.

Side effects:

• It may cause allergy, hypersensitivity, skin rashes, nasal congestion, etc.

Carboxylic acid sugars

• Monosaccharides with a carboxylic acid group, obtained by the oxidation of the carbonyl group or the hydroxyl group of monosaccharides.

Types:

1. Aldonic acid:
   • Obtained by oxidation of the aldehyde group of aldose into carboxylic acid.
   • Example: Gluconic acid
2. Uronic acid:
   • Obtained by oxidation of the first hydroxyl group of ketose sugar into carboxylic acid, resulting in the formation of 2-keto acid.
   • Example: Neuraminic acid
3. Usonic acid:
   • Obtained by the oxidation of the hydroxylic group of the terminal carbon of aldose or ketone to carboxylic acid.
   • They have two functional groups: carbonyl and carboxylic acid.
4. Aldaric acid:
   • Obtained by oxidation of the carbonyl and terminal hydroxyl groups of aldose into carboxylic acid.

Glucuronic acid

• Structure is similar to glucose, but the 6th carbon is oxidized to carboxylic acid.
• Glucuronic acid's anion is glucuronate.

Occurance:

• Produced in the human liver and in most animals.

Biological functions:

1. Detoxification:
   • Highly soluble in H2O. In the animal body, glucuronic acid is often linked to poisonous substances (mainly in the liver) to allow for subsequent elimination, and to hormones to allow for easier transport.
   • These linkages involve O-glycosidic bonds.
   • The process is glucuronidation and the resulting substances are glucuronides or glucuronosides.
2. Synthesis of Ascorbic acid:
   • Glucuronic acid is used to produce L-gluconic acid, which is a precursor of ascorbic acid.
3. Synthesis of glucosaminoglycans:
   • Glucuronic acid is a component of GAGs such as hyaluronic acid and chondroitin sulfate.
4. Synthesis of nicoprotein:
   • Uridine diphosphate - glucuronic acid is converted to units UDP-xylose, which is used in the synthesis of nicoprotein.
5. Drug metabolism
   • Phase II metabolism: Glucuronic acid is a key player in phase II drug metabolism, where it helps to convert lipophilic drugs into more hydrophilic forms.
   • This is crucial for elimination of drugs from the body.
   • Inactivation of drugs: By forming glucuronides, glucuronic acid can inactivate drugs, reducing their pharmacological effects and facilitating their excretion through urine or bile.
6. Bilirubin metabolism
   • Glucuronic acid is involved in the metabolism of bilirubin, a breakdown product of haemoglobin.
   • It conjugates with bilirubin to form bilirubin diglucuronide which is more water soluble and can be excreted in bile.
7. Cell Surface interactions
   • Glucuronic acid can be found on the surface of cells where it may play a role in cell interactions and signaling pathways.
   • It can influence the binding of proteins and other molecules to the cell surface.
8. Cancer Research
   • There is ongoing research into the role of glucuronidation in cancer, as altered drug metabolism can affect the efficacy of chemotherapy agents.

Gluconic acid

• Gluconic acid is the carboxylic acid formed by oxidation of the 1st carbon of glucose.
• When dissolved in water, it forms gluconate.
• Salts of gluconic acid are gluconates.
• In aqueous solution, some gluconic acid molecules will condense into cyclic ester glucono delta lactone, and the two exist in equilibrium.

Occurance:

• Gluconic acid occurs naturally in fruit, honey, kombucha tea, and wine and is used as a food additive and acidity regulator.
• It is a strong chelating agent, especially in alkaline solutions.

Biological functions:

1. Energy Source:
   • Gluconic acid can be utilized as an energy source by certain microorganisms and cells.
2. Intermediate in metabolism:
   • It serves as an intermediate in various metabolic pathways including the pentose phosphate pathway, which is crucial for generating NADPH and ribose-5-phosphate for nucleotide synthesis.
3. Detoxification
   • Gluconic acid has the ability to chelate (bind) metal ions, which helps in detoxifying heavy metals and facilitating their excretion from the body.
4. pH Regulation
   • Gluconic acid can act as a buffering agent, helping to maintain pH balance in biological systems. This is important for various processes including enzyme activity and metabolic reactions.
5. Role in bone health
   • Gluconic acid can enhance the solubility and absorption of calcium, which is essential for bone health.
   • It may help in prevention of conditions like osteoporosis by improving calcium bioavailability.
6. Preservative
   • It is used as a food preservative due to its antimicrobial properties.
7. Drug Formulation
   • Gluconic acid is used in pharmaceutical formulation as a stabilizing agent and to enhance the solubility of certain drugs.
8. Plant growth
   • It is used by plants and can influence plant growth and development. It plays a role in nutrient uptake and metabolism in plants.
9. Regulation of blood sugar levels
   • Some research indicates that gluconic acid may help in regulating blood sugar levels by influencing glucose metabolism.
   • This could have potential implications for diabetes management, although more research is needed.

Sugar phosphates

• Phosphorylated sugars are another important class of derivatives of sugars.
• At the normal pH of cells, most of the hydroxyl groups (-OH) on the phosphates are ionized (-O-).
• The hydroxyl group of sugar forms ester bonds with phosphates.
• They are often used in biological systems to store or transfer energy.
• They also form the backbone of DNA & RNA

Adenosine triphosphate (ATP)

• Adenosine 5'-triphosphate (ATP) is a multifunctional nucleotide that is most important as a "molecular currency" of intracellular energy transfer.
• Produced as an energy source during the processes of photosynthesis and cellular respiration

Structure :

1. Ribose sugar:
   • This is present at the anterior end of ATP and is a simple sugar containing a ring of 5 carbon atoms. This same sugar is also present in RNA.
2. Adenine:
   • Connecting to one side of the ribose sugar is adenine, a base which has N & C atoms in a double ring structure.
3. Phosphate:
   • On the other side of the ribose sugar are 3 phosphate groups.

• ATP has high energy content due to 2 phosphoanhydride bonds that connects the 3 phosphate groups.

Release of energy:

$ATP + H<em>2O \longrightarrow ADP + HPO</em>4$

• Under standard conditions, removal of 1 phosphate group from ATP releases 7.3 kcal/mol.

Biological functions:

1. It is consumed by many enzymes & multitude of cellular processes including biosynthetic reactions, motility & cell division.
2. Signal transduction pathways
   • ATP is used by kinases that phosphorylate proteins & lipids as well as by adenylate cyclase, which uses ATP to produce the second messenger molecule cyclic AMP.
3. Substrate for Enzymatic reactions
   • ATP is often used as a substrate in biochemical reactions, providing the necessary energy for metabolic pathways, including glycolysis, citric acid cycle & oxidative phosphorylation.
4. Muscle contraction
   • ATP is essential for muscle contraction. It provides energy required for the interaction b/w action and myosin filaments in muscle fibers, enabling muscle movement.
   • ATP is also required for pumping of Ca++ ions back into the sarcoplasmic reticulum, which is crucial for muscle relaxation.
5. Nucleic acid synthesis
   • ATP is a nucleotide that serves as a building block for RNA synthesis during transcription.
   • It is also involved in DNA synthesis as a precursor for deoxyribonucleotides
6. Thermogenesis
   • In certain tissues, such as brown adipose tissue, ATP can be used to generate heat instead of being converted into mechanical work. This process is important for thermoregulation in mammals.

Sugar Alcohols

• Sugar alcohols, also known as polyols, polyhydric alcohols, or polyalcohols, are hydrogenated forms of carbohydrates whose carbonyl group has been reduced to a primary or secondary hydroxy group.
• General formula = HO-CH2-(CHOH)n-CH2OH
• These are white, water-soluble solids that occur naturally in fruits, vegetables, etc.
• They not only give a sweet taste but also perform a variety of functions
• Maltitol is sweet compound formed from sorbitol.

Maltitol

• Made up of glucose and sorbitol.

Occurance:

• Found naturally in fruits and vegetables.
• Commercially, maltitol is a disaccharide produced by hydrogenation of maltose obtained from starch products.

Biological functions and uses:

1. Caloric content:
   • A sugar alcohol used as a sugar substitute (also known as table sugar alcohol) because it has few calories, does not promote tooth decay and has a somewhat lesser effect on blood glucose.
2. Sweetness level:
   • It has 30% of the sweetness of sucrose and nearly identical properties. Unfortunately, it is well known to cause gastric distress if consumed in great quantities.
3. Dental health:
   • It is not metabolized by oral bacteria, so it does not promote the formation of dental cavities.
   • This property makes it a preferred sweetener in sweets, sugarless hard candies, chewing gums, chocolates, baked goods, and ice creams
4. Lower Glycemic Response:
   • This property leads to slower and more gradual increases in blood glucose levels (slowly absorbed than sucrose), which makes it somewhat more suitable for people with diabetes than sucrose
5. Moisture Retention
   • It is used as a humectant, helping to retain moisture in food products.
6. Laxative effects
   • In some cases, excessive consumption of maltitol can have a laxative effect due to its osmotic properties.
7. Regulatory Status
   • Maltitol is generally recognized as safe (GRAS) by the U.S. Food & Drug Administration (FDA) & is approved for use in many countries around the world.

Side effects:

1. Laxative effect if consumed in large quantity.
2. Gastric distress
3. allergy trigger allergic reaction in sensitive individuals.

Lactitol

• Made from galactose and sorbitol
• 40% as sweet as sucrose

Occurance:

• Produced chemically by hydrogenation of lactose with metal catalyst at high temperature and pressure.
• Marketed as concentrated syrup and as a crystalline powder in the form of lactitol monohydrate.

Biological functions and uses:

1. Caloric content
   • Lactitol is a sugar alcohol used as a replacement and bulk sweetener for low-calorie foods with approximately 40% of the sweetness of sugar.
2. Osmotic laxative
   • Increases fecal volume, which helps to stimulate bowel movements
   • Provides relief from constipation by drawing water into the intestines.
3. Prebiotic effects
   • Promotes the growth of beneficial gut bacteria, particularly Bifidobacteria and lactobacilli.
   • Enhances gut health and may improve overall digestive function.
4. Cholesterol metabolism
   • May aid in the reduction of cholesterol levels by influencing bile acid metabolism.
   • Contributes to cardiovascular health by potentially lowering LDL cholesterol.
5. Liver health
   • Supports liver function and detoxification processes.
   • Can be beneficial in managing conditions like hepatic encephalopathy
6. Diabetes Management
   • Has minimal impact on blood glucose levels
   • Making it a safe option for individuals with diabetes.
7. Used in sugar-free candies, cookies, chocolates and ice creams
8. Used in a variety of low-energy foods or low-fat foods; high stability makes it popular for baking

Side effects:

1. Lactitol attracts water from the intestinal wall (osmotic effect), so it can cause diarrhea if consumed in excess.
2. Overdoses of lactitol can cause vomiting, loss of K+, muscle cramps, headache, etc.

Oligosaccharides

• Oligosaccharides are a class of carbohydrates that consist of a small number of monosaccharide units (nearly 3 to 10) linked together by glycosidic bonds.
• The monosaccharides can be of the same type (homo-oligosaccharides) or different types (hetero-oligosaccharides).
• Most common monosaccharides found in oligosaccharides include glucose, fructose, galactose, and mannose

STRUCTURE:

• The linkage between monosaccharide units in oligosaccharides occurs through glycosidic bonds.
• These bonds are formed through a condensation reaction, where a hydroxyl group from one monosaccharide reacts with the anomeric carbon of another, releasing a water molecule.
• If a glycosidic linkage is established between the lactol groups of two monosaccharides then a non-reducing disaccharide is formed.
• While, when one lactol group (-OH) and one alcoholic group are involved then a reducing disaccharide is formed.

Denoted as:

• Reducing → Glycosyl glycoside e.g. Maltose
• Non-Reducing → Glycosyl glycoside e.g. Saccharose

Glycosidic Bonds

1. α-Glycosidic bonds
   • Formed when the hydroxyl group on the anomeric carbon is in the axial position (downward orientation).
   • In maltose, the bond between 2 glucose units is an α (1,4) bond.
2. β-Glycosidic bonds
   • Formed when the hydroxyl group on the anomeric carbon is in the equatorial position (upward orientation).
   • In lactose, the bond between glucose and galactose is a β(1,4) bond.

$Nomenclature:$

• An abbreviated method of nomenclature is to use a three-letter designation | symbol for a monosaccharide & suffix 'f' or 'p' for furanose or pyranose.

$Saccharose can be written as: O-β-D-Fructf (2-1) α-D-Glucp$
$Maltose can be written as : O-α-D-Glucp (1-4) D-Glucp$

• Branching also occurs in oligosaccharides when one monosaccharide is bound to two glycosyl residues.
• The name of the 2nd glycosyl residues is inserted into the square brackets
• A trisaccharide which represents a building block of the branched chain polysaccharides amylopectin and glycogen is given as:

$O-α-D-Glucopyranosyl-(1-4)-O-[α-D-glucopyranosyl-(1-6)-]D-glucopyranose$

• The abbreviated formula for this trisaccharide is as follows:

$α-D-Glcp (1-4) Glcp$ $(\alpha1-6)-α-D-Glcp$

• The conformations of oligosaccharides, like peptides, can be described by providing the angles φ & ψ

PROPERTIES & REACTIONS

Physical Properties of Oligosaccharides

1. Solubility:
   • Generally soluble in water due to their polar hydroxyl groups. It can vary based on the chain length & structure.
2. Taste:
   • Many oligosaccharides have a sweet taste, which diminishes with increasing chain length.
   • Sucrose is sweeter than longer oligosaccharides
3. Molecular weight
   • Typically have Mol. Wt. ranging from about 3-10 monosaccharide units
4. M.p. and B.p
   • They do not have well-defined m.p. like crystalline solids. Instead, they may decompose upon heating
   • The bp are influenced by their mol. Wt. & structure
5. Hygroscopicity
   • Oligosaccharides can absorb moisture from the air, which can affect their stability & shelf life in food products.
6. Viscosity:
   • It can vary significantly based on conc. & mol.wt. of oligosaccharide solutions
   • Higher conc. & longer chains lead to increased viscosity
7. Optical activity:
   • They are optically active due to the presence of chiral centers in their monosaccharide units.
   • They can rotate plane-polarized light, and the specific rotation depends on their structure & concentration.
8. Crystallization
   • The crystalline behavior is influenced by the type of glycosidic bond & the presence of functional groups.

Chemical Properties of Oligosaccharides

• Non-reducing oligosaccharides do not have a free lactol group and so lack reducing properties, mutarotation & the ability to react with alcohols and amines.
• Oligosaccharides are readily hydrolyzed by acids, while they are relatively stable against alkalies.
• Saccharose hydrolysis is denoted as an inversion of the sugar the resultant equimolar mixture of glucose & fructose is called invert based on change of specific rotation during hydrolysis
• In saccharose, the rotation is +ve. while it is -ve in the hydrolyzate, since D- glucose rotation is sight is surpassed by the value of left-eating fructose.

$Saccharose + H<em>2O \longrightarrow D-Glucose + D-Fructose$$α</em>D = +66.5° \longrightarrow = +52.7° + α_D = -32.4°$
$α = -19.8$

• Cyclodextrins are prepared by the action of α-1,4-oligo-maltodextrin glucanotransferase, obtained from Bacillus macerans, on maltodextrins.
• Maltodextrins are, in turn, made by the degradation of starch with α-amylase.
• This glucanotransferase splits the α-1,4-bond, transferring glucosyl groups to the non-reducing end of maltodextrins & forming cyclic glucosides with 6-12 glucopyranose units
• The main product, β-cyclodextrin, consists of 7 glucose units is a non-hygroscopic, slightly sweet compound.
• In food processing, β-cyclodextrin is a suitable agent for stabilizing vitamins & aroma substances & for neutralizing the taste of bitter substances.

Polysaccharides

• Polysaccharides are a class of carbohydrates that consist of a large number of monosaccharide units (more than 10) linked together by glycosidic bonds.

Derivatives of polysaccharides → Glycosaminoglycans

• GAGs are mucopolysaccharides are long unbranched anionic polysaccharides.
• A GAG unit consists of a repeating disaccharide unit consisting of N-acetyl-hexosamine & a hexose / hexuronic acid, either or both of which may be sulfated.
• The combination of the sulfate group & the carboxylate group of the uronic acid residues gives them a very high density of -ve charge.

. Chondroitin Sulfate

• Repeating unit: N-acetyl galactose amine
• Chondroitin sulfate is a GAG, which is covalently linked to proteins forming proteoglycans.
• It is a linear heteropolysaccharide that consists of alternating sugars (N-acetyl galactosamine) & glucuronic acid.
• It is commonly sulphated at C4/C6 of galactosamine

Occurance

• It occurs naturally in the body. It was discovered in the cartilage in 1861 by the German chemist Fischer
• Chondroitin sulfate is one of the primary components of the extracellular matrix and is found in tissues like skin, bone, cartilage, blood vessels, and nerve tissues.

Biological functions and uses:

• The antioxidant, anticoagulant, antithrombosis & negative immunogenic properties of CS make it a promising material in biomedical research

Some of its imp. roles are:

1. Maintaining healthy joints / treatment of osteoarthritis
   • CS delivers nutrients to the joint cartilage, helps to inhibit the enzymes that decompose the joint cartilage & speeds up the formation of new cartilage
   • Hence its elasticity is maintained
   • The tight packing of CS with highly charged sulphated group could restrict the compression of cartilage & help in cartilage regeneration.
   • CS is used in dietary supplement as alternative medicine to treat osteoarthritis & it is used as a Symptomatic Slow Acting Drug (SYSADOA), for this disease in Europe and some other countries.
2. Role in the nervous system
   • CS has a predominant role in neural signal transduction & it improves the activity of the central nervous system.
3. In cancer therapy
   • CS has been explored in active targeting for cancer therapy due to their ability to target the CD44 receptor on the cancer cells.
4. Anti-Inflammatory properties
   • CS has been shown to exhibit anti-inflammatory effects which can help reduce inflammation in joint tissue, potentially alleviating pain & discomfort
5. Wound healing
   • CS is involved in wound healing processes, promoting tissue repair & regeneration
6. Potential Cardiovascular benefits
   • Some studies suggest that CS may have cardiovascular benefits such as improving endothelial function & reducing arterial stiffness
7. Skin Health
   • Due to its hydrophilic properties, CS is sometimes included in skincare products for its moisturizing effects & potential to promote skin elasticity

Side effects:

1. Gastrointestinal discomfort, nausea, or diarrhea.
2. Imp. for those on anticoagulant medications
3. Or with specific health conditions to consult healthcare provider before starting supplementation

Heparin

• Highly sulphated polysaccharide that was discovered in 1916 as an anticoagulant and has been used clinically since 1935.
• It is on the WHO list of essential medicine.

Occurance:

• It is a naturally occurring anticoagulant produced by basophils and mast cells.
• It is stored within the secretory granules of the mast cells & is released only into the vasculature at the site of tissue injury.

Structure:

• Heparin has Mol. wt. ranging from 3-3000 daltons
• It belongs to the glucosaminoglycan family of carbohydrate & consists of a variably sulphated repeating disaccharide unit.
• Most common disaccharide unit is usually composed of 2-0-sulphated iduronic acid and 6-0-sulphated N-sulphated glucosamine are linked by a 1,4- glycosidic bond.
• It's key pentasaccharide sequence has pre glucosamine 2- Iduronic acid residues.
• The central glucosamine residue has a unique 3-0-sulphate moiety
• Removal of this group results in total loss of anticoagulant property

Biological functions & uses:

1. As an Anticoagulant
   • It prevents the formation of clots & growth of existing clots within the gut.
   • It does not breakdown clots that are already formed but it allows the body's natural clot lysis mechanisms to work normally to breakdown the clot already formed.

Mechanism of action

1. Heparin binds to antithrombin (ATIII).
2. This binding causes a conformational change in ATIII
3. The antithrombin-heparin complex increases the inactivation of two main procoagulants factors Xa and thrombin This prevent the conversion of fibrinogen to fibrine which is necessary for clot formation.

Heparin is used as an anticoagulant in the following conditions:

• Acute coronary syndrome
• Atrial fibrillation
• Deep vein thrombosis (DVT)
• Pulmonary embolism

Preventing Pathogen Infection

• At the tissue injury site, the main purpose of heparin is defense against invading bacteria & other foreign materials.

As an anti-inflammatory drug

• The potential of heparin as an anti-inflammatory drug has been shown by clinical trials with patients suffering from Bronchial Asthma, Ulcerative colitis
• This effect is due to the ability of heparin to alternate the interaction b/w leukocytes and various endothelium.

Side-effect

• Its overdose can result in excessive bleeding.