Bio-Chemical Nature of Human Body

Circulation, Distribution and Molecular Reactions Means Driving Bio-Energy Force

Hormones •Atoms (C,H,O,P,N,S,minerals)

Free Radical Diseases
Receptors
•Molecules
Enzymes Molecular Diseases
•Super-Assemblies
A + B  P1 P2 Structural Diseases
Carbohydrates •Organelles, skeleton
Amino Acids/Proteins Organelle Diseases
•Cells
Lipids Cell Diseases

Nucleic Acids •Tissues

Tissue Diseases
Vitamins/Minerals •Organs
Organ Diseases
•Systems
Lecture 3 + LIVE HUMAN
DRIVING ENERGY BODY
 Properties of Carbohydrates
• Stereoisomerism: Reference carbon atom
• D- and L- isomerism
• Optical Activity
• Diastereoisomerism (Glucose, Galactose, Mannose)
• Epimers
• Hemiacetal ring formation, Anomers and
Mutarotation
• Enediol formation (Glucose  Fructose) Glucose

• Oxidation of sugars
• Furfural by Sulfuric Acid and complex with Phenolic
compound (Molisch Test)
• Esters and Amino Sugars Lactose
• Deoxy sugars
• Osazone formation

Maltose
 Lecture
CARBOHYDRATES: Monosaccharides,
Disaccharides, Polysaccharides
• Polyhydroxy derivatives having CH2O structure
•Monosaccharides:
Glucose, Galactose, Mannose, Fructose(1 unit)
• Disaccharides:
Sucrose, Maltose, Lactose (2 units)
• Polysaccharides:
Starch, Glycogen, Dextrin, Cellulose(n units)
• Mucopolysaccharides
 Monosaccharides: One ring
• Aldose (Ribose, Glucose, Mannose,
Galactose), Ketose (Dihydroxyacetone,
Ribulose, Fructose) sugars
• Sialic Acid, β-D-Acetylgalactosamine,
β-D-Acetylglucosamine
• Cupric ions(Fehling Solution) +[-CHO-X] Cu2O
• Benedict test, Saliwanoff test, Barfoed test
confirm it

Rakesh Sharma for 1st MBBS Biochemistry

8/22/2013 4
Students
 Glucose:
Child of all Carbohydrates to Make Energy In Human Body

• Pyranose ring structure and Open Chain Structure

 Shows reducing properties due to H–C=O group
making red color complex (Molisch, Benedict
tests)
Shows Muta-rotation,
Isomerization, Phosphate Binding,
Amino- Substitution reactions
 Involved in Glycolysis, TCA cycle, Glycolipids
and Glycoprotein formation in metabolism
 Monosaccharides:
Glucose is The Child of All carbohydrates
•Pyranose Ring
Formation: hemiacetal
formed by reaction
between the aldehyde
group and a hydroxyl
group
•Stereochemistry and
Isomerism
Monosaccharides:Examples
More Examples
Derived Monosaccharides
Monosaccharides make
compounds as Phosphates,
Sulphates, Acids, Esters, Amino
sugars, Glycosides (Glucoside,
Galactoside, Fructoside,
Mannoside), Uronic
derivatives(Glucuronate,
Iduronate, Deoxy Sugars
(Deoxyribse, Fucose,
Deoxyglucose, Glycoproteins
and Sialic Acid
Glycomics:Amino Sugars, Glycoproteins,
Acidic Sugars in Carbohydrates

8/22/2013 10
Glycomics:Amino Sugars, Glycoproteins,
Acidic Sugars in Carbohydrates
Glycomics:Amino Sugars, Glycoproteins,
Acidic Sugars in Carbohydrates
Glycomics:Amino Sugars, Glycoproteins,
Acidic Sugars in Carbohydrates
Glycomics:Amino Sugars, Glycoproteins,
Acidic Sugars in Carbohydrates
 Glycoproteins
• Glycoproteins made of oligosaccharides plus a
protein.
• Glycoproteins are:
 Glycocalyx on plasma membrane,
 Found in the extracellular matrix, and blood groups.
 Golgi complexes, secretory granules, and lysosomes.
 The oligosaccharide portions + proteins called lectins.
 Some cytosolic and nuclear proteins are glycosylated(UDP-
Gal/Glu/Gal-NAc/Glu-NAc;GDP-Mannose/Fucose)
 Peptide hormones.
 Metastasis glycoproteins on surface of cancer cells
 Diseases due to Glycoproteins
• Cancer
Advanced Glycation End-Products(AGE)
in Diabetes Cause Tissue Damage
• Glucose+ProteinAGE (Millard Reaction)
AGEs do vascular wall damage in poor controlled
diabetes(Glycation of collagen, ECM results with
poor cross linking, high LDL –ATHEROSCLEROSIS)
AGEs receptors on endothelial cells activate
Cytokines (Inflammation)
Glucose+hemoglobin AHbA1c
(Diabetes Control)
 Disaccharides

Sucrose (D-Glucopyranosyl(12) β -D-

Maltose (D-Glucopyranosyl- Fructofuranose)
(14)-α-D-Glucopyranose.
•Enzyme Hydrolysis by
Disaccharidase Enzymes break down a
Disaccharide into two monosaccharide
units

Lactose (D-Galctopyranosyl(14)-β-D-Glucopyranose)
 Polysaccharides: Starch and Glycogen
Amylose Glycogen

Starch (Amylose α-1,4 linkage;

Amylopectin α-1,6 linkage
Cellulose (β-1,4 linkage)
Glycogen (two glucose molecules
Amylopectin join by α-1,4-glycosidic bonds Branched chains
and make branch point α-1,6-
glycosidic bonds)
 Polysaccharides: Starch and Glycogen
Starch Amylose straight chain Glycogen

Starch (Amylose α-1,4 linkage in

straight chain; Amylopectin make
α-1,6 glycoside linkage in branch chain
Amylopectin Cellulose (β-1,4 linkage)
Glycogen (two glucose molecules Branched chains
join by α-1,4-glycosidic bonds
and make branch point α-1,6-
glycosidic bonds)

Straight Chains
 Glycosaminoglycans: Anionic Chain of
Repeat Disaccharides(Harper p157)

Heparan Sulphate
Hyluronic Acid
Keratan sulphate
Dermatan sulphate
Chondroitin Sulphate
 Blood Group: Glycosides on RBC
• On RBC Surface, Human ABO group oligosaccharide antigens
have: GlcN-Ac(A), galactose(B) and fucose(O)
-Mismatch of blood group
• is due to Glucotransferase
• enzymes

Fuc Fuc Fuc

• Selectin
• Hemagglutinins
 Cerebrosides and Gangliosides
• Glycosphingolipids (cerebrosides and
gangliosides)
• Glycolipids (glycosphingolipids) have a
fatty acid, sphingosine, and
carbohydrate
• Cerebrosides have a single sugar linked
to ceramide
• Gangliosides (sphingolipids) have
oligosaccharides polar head groups +
one N-Acetyl-Galactosamine(NAG) +
residues of N-acetylneuraminic acid
(NeuAc) or sialic acid Ganglioside
(A sphingolipid)
 Diseases of Carbohydrates
• Glucose Loss in urine: Glucosuria
• Glucose High in blood: Diabetes Mellitus
• Fructose high in urine: Fructosuria
• Lactosuria or (Urine has Undigested Lactose):
Lactose Intolerence
• Glycosaminoglycan deposits
(Mucopolysaccharidoses)
Diseases of Disaccharides and Polysaccharides
• Glycosaminoglycan deposits(Mucosaccharidoses)
HURLER Syndrome; HUNTER Syndrome; SANFILIPO A
and B Syndrome; MORQUIO Syndrome; MORTEAUX-
LAMY Syndrome; SLY Syndrome
• I-cell disease(Mucolipidosis II)-Missed Mannose 1-P
required to send 8 hydrolytic enzymes from Golgi Body
to Lysosomes
• Glycogen Storage Diseases (VON GIERKE Disease;
Pompe’s Disease; Cori’s Disease; Anderson’s Disease;
McArdle’s Disease; HER’S Disease; TARUI Disease)
• Cerebrosides and Gangliosides (Cerebrosidoses and
Gangliosidoses)
 Diseases of Glycosaminoglycans and Glycogen
Mucopolysaccharidoses (Glycosaminoglycans) Harper p639
• HURLER or SCHEIE syndrome: Dermatan sulphate deposits(iduronic acid – N-
acetylgalactosamine) in skin, lung; deposits of Heparan sulphate(Glucuronic Acid –
Glucosamine) in lung, liver, muscle  Cornea clouds, Hepatomegaly
• HUNTER syndrome: Dermatan sulphate and Heparan sulphate deposits in lung,
liver, muscle, brain  Mental Retardation
• SANFILIPO A and B Syndrome: Heparan Sulphate deposits in lung, liver, muscle
• MORQUIO syndrome: Keratan sulphate (Galactose – N-acetylgalactosamine)
deposits in cartilage; and chondroitin sulphate in cartilage  Bone Dysplasia
• MAROTEAUX- LAMY syndrome: Dermatan sulphate deposits in skin, lungSpine
• SLY syndrome: Dermatan sulphate deposits in skin,lung; and Heparan sulphate
deposits in lung, muscle, liver Short Bones, Hepatomegaly, Cloudy cornea

Glycogen storage Diseases: Harper p179nzyme defects will be discussed later

• Von Gierke Disease- High glycogen in liver, kidney
• Pompe’s Disease- High glycogen in all organs
• Cori’s, Forbe’s Disease-High glycogen in heart,liver, muscle
• Anderson’s Disease-Normal glycogen (with long outer branches in liver, spleen,
muscle)
• McArdle’s Disease-High glycogen in muscle
• Her’s Disease- High glycogen in liver
• Tarui Disease-High glycogen in muscle
Lactosuria: Lactose indigestion
20 y male complained of macroglossia in
OPD. What are causes ?

Answer: Mucopolysaccharidoses and Glycogen Storage Diseases

 Gangliosidosis Harper p218

Ganglioside Storage Disease:

Gangliosidosis(GM1) (Cer-Glu-Gal-
GalNAc-Neu5Ac-Gal deposits)
Tay-Sachs Disease(GM2) (Cer-Glu-Gal-
Neu5Ac-Gal N Ac deposits)
(GM3) (Cer-Glu-Gal-Neu5-Ac deposits)
Gaucher’s Disease (Cer-Glu deposits)
Sandhoff’s Disease (Cer-Glu-Gal-Gal-N-
Ac deposits)
Fabry Disease (Cer-Glu-Gal-Gal
deposits)
 CARBOHYDRATES: Clinical Biochemistry,
Medical Biochemistry, Thera-nostics
CLINICAL BIOCHEMISTRY: MEDICAL BIOCHEMISTRY:
• Glycogen •Glycosaminoglycan Storage
• Urine Mucopolysaccharides Diseases
• Urine sugar •Glycogen Storage Diseases
• Urine lactose •Hemolysis and Blood Groups
• Inulin Clearence Test •Cerebrosides and Gangliosides
Diseases
THERA-NOSTICS
•Lactose intolerance and Infant Milk Formula
•Disaccharidase enzyme Deficiency by pills (Aristozyme)
•Blood Transfusion by right blood group A,B or O
•Penicillin kills N-Acetyl Murmuric Acid-Glucosamine
(NAM-NAG) in bacterial cell wall
•Dextran as plasma volume expander for HYPOVOLEMIA
•Mannitol injection is given to relieve hematoma pain
 Biochemistry in Thera-nostics:
Decision Making of Disease Burden and therapy

• Physical Diagnosis(signs and symptoms)

• Laboratory Investigations
•Disease/Drug induced change in:
Integrated Lab tests •3D Structure of molecules,
Chemistry,
•Regulatory Kinetics of Enzymes,
• Molecular Diagnosis Hormone actions, Receptors
•Metabolic control,

• Therapeutic Monitoring •Molecule size, shape,

localization, bioimaging
BIOCHEMICAL DISEASE BURDEN CONFIRMED AND
THERAPY RESPONSE IS GOOD
• Referral to nodal Medical Center
• Open for Discovery
 Problem Based Learning
1.A blood sample for glucose is taken from 50
year old woman after an overnight fast. Which
one of the following will change concentration
than after she eats full meal? What indications?

2.A blood sample is taken from 40 year old man

on week-long fast only drinking water. Which
one of the following will be at a higher
concentration than after he is on overnight fast?

Choice: Glucose; Insulin; Ketone bodies; Fatty Acids; Triglycerides

 Problem Based Learning
Chabbra p1

20 y man suffered from

breathlessness,
(congestive heart
failure), hospitalized.
Started with
digoxine(digitalis). After
few days discharged.

Q. What are glycosides? and digitalis?

Q. How digitalis act? Why patient
improved?
 Examination Questions
• Describe carbohydrates (monosaccharides,
disaccharides, polysaccharides), classification,
chemistry with structures.

• Short questions:
 Monosaccharides
 Disaccharides
 Mutarotation
 Isomerism and anomers
 Glycogen storage diseases
 Mucopolysaccharidoses
 Cerebrosides and Gangliosides
Carbohydrates are digested in
Stomach and Intestine with
help of Enzymes and Energy
 Enzymes Catalyse Carbohydrate
Digestion and Absorption Using ATP
• What are enzymes?
Monosaccharidase, Disaccharidase, Amylase
• How ATP is used and ATP is formed in the
body?
Bioenergetics, ADP+iPATP (Kinases)
 ENZYMES
• ENZYMES (CATALYST PROTEINS) ACCELERATE SUBSTRATE-
SPECIFIC BIOCHEMICAL REACTIONS(REDOX,GROUP
TRANSFERS,HYDROLYSIS,PHOSPHORYLATION,LYSIS,ISOMERI
ZATION, SYNTHESIS) BY FORMING 3D ENZYME-SUBSTRATE
COMPLEX WITH COFACTOR and COENZYME AT OPTIMAL
pH AND TEMPERATURE.
Enzyme + Substrate  [ES] Product
• ENZYME INHIBITION REGULATES METABOLISM

• USE OF ENZYME INHIBITORS IN MEGA-DRUG INDUSTRY

 High-Energy Phosphates

Structure of ATP

Figure 3.10
 Digestion and Absorption of
Carbohydrates
Polysaccharides, Disaccharides  Monosaccharides

Absorbed

Metabolized to make ATP

(Carbohydrate Metabolism)
Digestion of Carbohydrates
• Salivary α-Amylase:
 α(14) Endoglucosidase at pH 7.4
 Undigested α(16) bonds in Starch
makes Dextrin
• Stomach low pH
• Pancreas α-Amylase:
 HCO3- Neutralizes acidity
• Intestine Disaccharidases:
 Maltase: α(14) 2 Glucose
 β-Galactosidase:β(14) Glu+Gal
 Sucrase: α(12)  Glu + Fructose
 Absorption of Monosaccharides
• In duodenum and upper jejunum,
monosaccharides are absorbed.
• In mucosal BBM cells,
Na+-ATPase dependent Glucose Co-
transporter (SGLT-1) facilitates
Glucose,Galactose absorption.
GLUT-5 facilitates Fructose absorption
GLUT-2 facilitates all monosaccharides to
portal circulation
 Disaccharidase Deficiency
• If any Disaccharidase enzyme is deficient
Genetic Disease [Undigested disaccharides+
Accumulated CO2+H2 pass in large intestine]
Diarrhoea, Abdomen Cramp, Flatulance
• Drug induced BBM mucosa damage, Malnutrition
cause Diarrhoea due to Less Diasaccharidase
enzymes or Intolerance
• Lactose Intolerance due to Lactase Deficiency
 Problem Based Learning-2
• A 40 year old man complained
diarrhoea, abdominal cramp with
frequent farting. A urine sample Glucose

showed Barfoed test positive but

Benedict test negative. Sample sent
to AIIMS. It showed Osazone test Lactose
positive.
Mechanism?
Maltose
Diagnosis? Disaccharide Intolerence
Treatment: Disaccharidase pills.
 Problem Based Learning-3
• A young man showed up with complaints of unable
to digest diary products, diarrhoea, bloating after
ice-cream contest party (couldn’t eat ice-cream);
physical exam: eyes sunken, dehydration, normal
temperature; Lab test showed very low
disaccharidase enzyme.
Mechanism?
Choice: Low Isomaltase,Lactase,Pancreas/Salivary
Amylase, Sucrase
 Problem Based Learning - 4
• Mother complained of her new born baby 15
days old with repeated vomiting soon after
milk drinking. Upon examination, lab tests
were: low lactase.
What milk is good for baby?
Lectose Intolerence
• Physical Symptoms:
Cramps, Diarrhoea
• Mechanism: Lactase
Deficiency due to
Chromosome 2(DNA)in
90% Euro-Africans
• Lab Test: H2 breath test
• Treatment: Only lactose
free milk, Egg yogurt,
cheese,broccoli juice;
Lactase pills
 Exam Questions
• Describe digestion and absorption of
carbohydrates in the body. Give an account of
disaccharide malabsorption across small
intestine.
• Short Notes on:
Lactose Intolerence
Disaccharidase deficiency
Absorption of carbohydrates