1_biochem - carbohydrates & lipids

7/25/2019 1_Biochem - Carbohydrates & Lipids

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CARBOHYDRATES


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Definition

Polyhydroxy aldehydes or ketones Or prothem on hydrolysis.

Water soluble in Nature

1 gm of carbohydrate Yield 4.5 Kcal of en

Can be stored in body

Performs various functions


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Classification

1. Monosaccharidesa. Aldoses

b. Ketoses

2. Oligosaccharidesa.Diasaccharides

b.Trisaccharides

c.Tetrasaccharides


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Monosaccharides

No. of carbons Aldose (- CHO) Keto

3c Glyceraldehyde 3P D

4c Erythrose 4 P Eryth

5c Ribose 5P Rib

6c Glucose 6P Fru


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Derivatives of Monosacchar

1. Sugar acids2. Sugar alcohols

3. Osazones4. Phosphoric acid esters

5. Amino sugars


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Disaccharides: Biomedical imporName Linkage Importance

Maltose

(Glu+Glu) (1 -> 4)

Formed in GIT on digestio

and glycogen by amylase

Lactose

(Gal+glu)

(1 -> 4)Sugar present in milk

Sucrose

(Glu+fru)

(1 -> 2)Table sugar

Isomaltose

(Glu+glu)(1 -> 6)

Formed in GIT on digestio

and glycogen by amylase

Trehalose

(Glu+glu)(1 -> 1) Present in the diet


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PolysaccharidesHomopolysaccharides

1. Starch (1

4 and 1

6)

2. Glycogen(1

4 and 1

6)

3. Dextrins (1

4 and 1

6)

4. Dextran (1

4 ,1

6 and 1

3)

5. Cellulose (14)

6. Chitin (Nac Giusamine, 1

4)

7. Inulin( Fructosan)

8. Agar(Galactasan)


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Heteropolysaccharides

Name

Repeating

Disaccharides Oc

Hylaluronic acid D-Glucuronic acid-N-

acetyl glucosamineJoints, O

Chondroitin sulphate

D-Glucuronic acid-N-

acetyl galactosamine4 S/6S

Cartilag

HeparinGlucoronic acidN-S-

glucosamineMast


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Heteropolysaccharides

Name Repeating

Disaccharides

Occur

Dermatan

sulphate

Iduronic acid-N-

acetyl

galactosamine 4S

Skin,v

blood v

Keratan Sulphate D- Galactose-N-

S- glucosamine

Cartila

Cor


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Glycoproteins/Proteoglyca Extracellular Macromolecules

Depending on their carbohydrate and protein coare classified as--

1.Glycoproteins-Carbo< proteins

-Oligosaccha.(1-20), branched

Eg- Igs, Transferrin ets 2.Proteoglycans-Carbo> proteins

-Longer(100), Linear, Unbranched

Eg.- Decorin, Perlecan ,aggregan


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Glycoproteins There are 2 types of glycoproteins

1.O-linked

2.N-linked

Functions of glycoprotein

1. Lubrication2. Cell adhesion

3. Cell recognition

4. Sugars in Glycoprotein stabilizes protein again

degradation, protect from proteolysis


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Structure of glycoprotei Polypeptide chains of proteins

covalently linked to oligosaccharide

chains of carbohydrate

There maybe 1-30 or even more

oligosaccharide chains

The no. of mono saccharide residues

may vary from 1-2 to much larger

The mono saccharide residues are

mainly xylose, fucose, gal, man, gluN,

galN, manN, NANA

aa

aa

aa

aa

gal


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Glycoprotein degradation

Lysosomal enzymes glycosidases1. Exoglycosidases

2. Endoglycosidases

Genetic deficiency of these enzymes results indegraded glycoproteins and oligosaccharides i

These disorders are termed as glycoprotein sto

diseases.


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Proteoglycans

Functions

1.Polyionic

2.Highly hydrophilic

3. Forms gel like substance acts

as lubricants and cushions4.Provides rigidity and stability to

connective tissue

5.Mediate cell -cell interactions


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Mucopolysaccharidosis

Type Syndrome Enzymatic DefectA

I Hurrlers Alpha-L-Iduronidase

II Hunters Iduranate Sulphatase

III Sanfilippos Heparin Sulphasate

IV MorquiosGalactosaminesulphat

ase


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Type Syndrome Enzymatic DefectAc

V Scheies L-Iduronidase

ViMaroteaux-

Lamys

N-

Acetylgalactosamin

e-4-sulphatase

vII Slys Beta-Glucoronidase


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Digestion and absorption

Starts in mouth: Salivary amylaseStomach: No significant digestion

Small Intestine: Sucrase,Lactase,Maltase,Iso

pancreatic Amylase

Digestive products: Glu,Gal,Fru,

Absorption :GLUTS (1-7)

Mode of absorption: facilited transport and Se


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Glycolysis

Only pathway which can operate in bconditions:

1. Aerobic ( In presence of Oxygen)

Glucose ------> Pyruvate

2. Anaerobic(In absence of Oxygen)

Glucose ------> Lactate


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Glycolysis1. Location: Most of the mammalian cell

2. Site: Cytosol

3. Precursor: Glucose

4. End product: Pyruvate/Lactate

5. Significance: Energy ( ATPs)6. Regulatory Enzyme: a. GK/HK

b. PFK

c. PK


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Energetics of glycolysis


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Energetics of glycolysisEnzyme Type of

phosphorylation

No. of

Glucokinase/Hexokinase -

Phosphofructokinase -

Glyceraldehyde 3P

dehydrogenase

Oxidative 3 +

Phosphoglycerate Kinase Substrate Level

Pyruvate Kinase Oxdative 1

Total 10


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Link between Glycolysis and Pyruvate dehydrogenase complex (PDH)

Multienzyme complex

Requires 5 coenzymes

NAD+

TPP

Lipoic acid

CoA

FAD


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TCA/Citric Acid Cycle/KrebsC1. Location: Cells containing Mitochondria

2. Site: Mitochondrial Matrix3. Precursor: Acetyl CoA

4. End product: ATPs+ CO2+H2O

5. Significance: Energy ( ATPs)

6. Regulatory Enzyme: a. Citrate Synthase

b. Isocitrate DHGNS

c. -KG DHGNS

d. Succinate- thiokinase


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TCA/Citric Acid Cycle/KrebsC

Special features:

1. Anabolic + Catabolic role = Amphibolic

2. Produces Plenty of energy

3. Links various metabolic pathways4. Plays Important role in metabolic switch

eg. Extra glucose is converted to Fat


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Energetics of TCA

Enzymes Phosphorylation No. of AT

Isocitrate dehydrogenase Oxidative 3 (2.5)

-KG dehydrogenase Oxidative 3 (2.5)

Succinate Thiokinase Substrate level 1

Succinate dehydrogenase Oxidative 2 (1.5)

Malate dehydrogenase Oxidative 3 (2.5)

Total 12 or 10

Gl i


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Gluconeogenesis1. Location: Mainly in liver and kidneys

2. Site: Mitochondrial Matrix and cytosol

3. Precursor: Lactate,pyruvate,isocitrate,-KG,Succinyl

CoA,Glycerol,Odd chain Fas,glucogenic AA

4. End product: Glucose

5. Significance: Synthesizes glucose from non carbohyd

6. Regulatory Enzyme: a. PC

b. PEP-CK

c. Fru 1,6 BPtase

d. Glucose 6 Ptase


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HMP shunt


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HMP shunt1. Location: Adrenal cortex,lactating mamm

glands, gonads

2. Site: Cytosol


4. End product: NADPH and fru 6 P, Gly 3P

5. Significance: NADPH ,Ribose5P

6. Regulatory Enzyme: a. Glucose 6P DHGN

b 6 P gluconate DH


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Significance of HMP shun

1. Provides two important intermediates

a. NADPH + H+

- Required for synthetic pathways like F

synthesis, Cholesterol synthesisb. Ribose 5P

- Pentose sugar present DNA,RNAs and

Nucleotides

Disorders of HMP shunt


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Disorders of HMP shunt

1.Glucose 6 phosphatase deficiency

-No NADPH No reduction ofglutathioneDrug induced Oxidativ

can not be metabolised leads to hem

anaemia.

2.Wernicke- Korsacoff syndrome

TPP deficiency especially in alcoholi


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Uronic acid pathway

1. Location: Adrenal cortex,

2. Site: Cytosol


4. End product:

5. Significance: Provides Glucuronic ac

Ascorbic acid


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GlyMet

Glycogen metabolism


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Glycogen metabolismIntroduction

Glycogen metabolism involves 2 pathways

Glycogenesis: synthesis of glycogen from glucose

Glycogenolysis: breakdown of glycogen to form glu

Pathways occur in the liver and skeletal muscle

The protein on which the glycogen molecule is is called glycogenin. This protein is also an enzy

catalyzes the addition of first few molecules of

itself

M t


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Management

In disorders leading to hypoglycemia

administration of uncooked cornstarnasogastric feeding between meals i

required

In disorders leading to muscle fatigu

fructose infusion during exercise is th

preferred treatment.

i d f G l b


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Disorders of Galactose Metab

Galactosemia

1. Galctokinase

2. Galactose 1 P uridyltransferase (classical) -Galactosemia,Galactosuria,Hypoglycemia,A

1PDecreased PiLiver DysfunctionGlycogen storage in liver, Galactitol/dulcito

Cataract in earlyage.Hemolysis(lowNADP

3. Epimerase (Rare)

Disorders of Fructose Metabo


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1. Essential fructosuria (Rare)

-Fructokinase is deficient

- High plasma fructose-Fructosuria

- Asymptomatic

1. Hereditary fructose intolerance

a. Aldolase B

b fructose 1 6 Bi phosphatase

Diabetes mellitus- metabolic rearran


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Diabetes mellitus metabolic rearran

Insulin Deficiency-decreased glucose uptake

Decreased of Glycolysis

Increased of gluconeogenesis

Increased glycogenolysis

Decreased glycogenesis

Increased Lipolysis

Decreased lipogenesis

Increased proteolysis

Di b lli h


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Diabetes mellitus- other consequ

1. Glycosylation of proteins. eg-Hemoglobin, albumin

2. Sorbitol pathway: Accumulation

sorbitol leads to Cataract, nephrand peripheral neuropathy.

Li id


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Lipids

Organic, insoluble molecules whisoluble in organic solvents.They a

esters of Fatty acids with alcohol

actually or potentially related to acids.

Cl ifi ti


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Classification

1. Simple lipids: Fats /oils (TAG)and2. Compound lipids: PL,GL,SL,LP

3. Derived lipids: FA,Alcohols,Chole

Digestion and absorption of l


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Digestion and absorption of l Mouth: Lingual lipase

Stomach :Gastric lipase

Small intestine: Pancriatic LipasePhospholipase

Cholesterol esterase

EmulsificationMicell formation

Adsorption of FFA, Glycerol,LysoPL,Chole

Resynthesis of LipidsPacked in Chylomicron

Lipid transportation


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Lipid transportation Lipoproteins

Chylomicrons- Apo B48,TAG,Chole-E(InstLiver)

VLDL-ApoB1oo,TAG,Chole-E (LiverPe

IDL-ApoB100,Chole-E (LiverPeripher

LDL-ApoB100,Chole-E (LiverPeriphe

HDL ApoA Chole E(Periphery Liver

Beta oxidation of Fatty aci


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Beta oxidation of Fatty aci1. Location: Peripheral tissue

2. Site: Mitochondrial matrix3. Precursor: Acyl CoA

4. End product: Acetyl CoA

5. Significance: Energy ATPs

6. Regulatory Enzyme: carnitine acyl c

transferase I


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Energetics


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Enzyme/ Reaction ATP

Acyl CoAdehydrogenase FADH2 2 x7=14 or 1

Enoyl CoA

Dehydrogenase

NADH+H+ 3x7=21 or 2

Acetyl CoAOxdaition

TCA 12x8=96

Total =131-2=

=108-2

FA synthesis


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FA synthesis

1. Location:Liver,Lactating mammary glands,A

tissue,Kidneys,Brain2. Site: Cytosol

3. Precursor: Acetyl CoA

4. End product: Acyl moeity(Palmitate)5. Significance: Fatty acid-Required for synth

other compounds

6. Regulatory Enzyme: acetyl CoA carboxylase


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Chain Elongation


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Chain Elongation

Two types

1. Microsomal

2. Macrosomal

3. Endoplasmic Reticulum (Desatu

Cholesterol biosynthesis


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Cholesterol biosynthesis

1. Location:Liver,adrenalcortex,Intestine,ovar

Skin,Arterial wall etc.

1. Site: Cytosol and ER

2. Precursor: Acetyl CoA

3. End product: Cholesterol4. Significance: Cholesterol-Required for synt

other compounds

5. Regulatory Enzyme: HMG-CoA Reductase


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lipoproteins


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lipoproteins

1. Chylomicrons

2. VLDL

3. IDL4. LDL

5 HDL

Types of hyperlipoproteine


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Types of hyperlipoproteineType Lipoprotein fraction elevated

1 Chylomicrons2a LDL

2b LDL+VLDL

3 Chylomicron remnants and IDL

4 VLDL

5 VLDL + Chylomicrons

Prostaglandins


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Prostaglandins

Derivatives of arachidonic acid commonly

as eicosanoids.

Local Hormones-Autocrine, Paracrine

Inflammatory mediators(Fever)

Vasoconstrictor

Vasodialators

U i i


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