Download MBBS Biochemistry PPT 74 Atherosclerosis Lipid Disorders Lecture Notes

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Lipid Disorders

Role of Cytochrome P450 7A1(CYP7A1) /

7 Alpha-Hydroxylase /Cholesterol 7-Alpha

-Monooxygenase
? Cytochrome P450 7A1 is enzyme in ER of Hepatocytes

? Encoded by CYP7A1 gene

? Important role in cholesterol catabolism

? Catalyzes first rate limiting step in bile acid biosynthesis

? Oxidizes Cholesterol at position 7 using molecular Oxygen

? Converts Cholesterol to 7-Alpha Hydroxy Cholesterol

? Regulates Cholesterol level

? Bile acids provide feedback inhibition for CYP7A1

? Inhibition of cholesterol 7-alpha-hydroxylase (CYP7A1)

represses bile acid biosynthesis

? When blood cholesterol levels are high CYP7A1 is

upregulated by nuclear receptor LXR

? To increase production of bile acids and reduce level of

cholesterol in hepatocytes.

? When blood cholesterol levels are low it is downregulated

by Sterol Regulatory Element Binding Proteins (SREBP)


Salient Biochemical Features

Defect in CYP7A1 Gene

? Inherited through family

? Signs of premature cholesterol gal stone disease

? Defective Cholesterol Catabolism

? LDL Cholesterol levels elevated in blood

? Substantially elevated TAG

? Nonresponsive Statin therapy

? Increases risk of Atherosclerosis


Study Of Atherosclerosis

? Features of Normal and Atherosclerosed artery
? Risk of development
? Process of development
? Consequences
? Diagnosis
? Management
? Prevention and Reduction

Features Of Normal Arterial Wal

? Lumen of healthy arterial wal is lined by:

?Confluent layer of Endothelial cel s


Normal Endothelium Controls

Important function Of Arterial wal

vNormal healthy arterial endothelium:
vArteries are soft and Elastic
vRepels cells and inhibits blood clotting

vRegulates tissue and organ blood flow by

vAbility of blood vessels to dilate-

vasodilatation

vAbility of blood vessels to constrict-

vasoconstriction
Arteriosclerosis

What Is Arteriosclerosis?

? Arteriosclerosis is non-specific term used

to describe

? Hardening and thickening of wal of

medium or large arteries.


Atherosclerosis

is a form of

Arteriosclerosis

What Is Atherosclerosis?

? Term Atherosclerosis, comes from

Greek words



?Atheros- meaning "gruel" or "paste"

?Sclerosis- meaning "hardness".
Terms related to Atherosclerosis

? Many terms are associated to Atherosclerosis:

vAtheroma
vAtherosclerotic Plaques
vFibro Fatty Lesions
vFibrous Plaques

? Atherosclerotic Plaque Results

From Accumulation of :

?Lipids

?Connective tissue

?Inflammatory cel s

?Smooth Muscle cel s

?Foam Cel s

?Minerals

? In an intima of blood vessels.


Atherosclerosis is

Hardening of Blood Vessels

due to formation of

Fibro Inflammatory Fatty Lesions/Plaques

? Atherosclerosis are abnormal

Diseased/defective arteries.

? Becomes hard and non elastic

? Less or non Functional

? Decreased diameter of lumen

? Obstruct normal blood flow to

cel s/tissues/organs.
Causes Of Atherosclerosis

Risk Factors For Atherosclerosis

? Risk factors which accelerate

progression of Atherosclerosis

and endothelial dysfunction are:

?Oxidative Stress due to free radicals

?Dyslipidemias/Dyslipoproteinemias

?Hypercholesterolemia

?Other Cardiovascular risk factors
Improper Dietary Habits

? Eating an imbalanced diet
? Excess of Refined Sugars
? Excess of Saturated fatty acids
? Use of Trans Fatty acids

v Smoking
vAge and Sex
vPhysical inactivity
vStressful life style
?Hormonal Imbalances

vDiabetes mel itus
vMetabolic Syndrome

Unchangeable Risk factors of Atherosclerosis

? Age

? Genetic Alterations

? Male gender

? Men are at grater risk than are premenopausal

women, because of the protective effects of natural

Estrogens.

? Family history of premature coronary heart disease

? Several genetically determined alterations in

lipoprotein and cholesterol metabolism have been

identified.
Changeable Risk Factors Of

Atherosclerosis

vHyperlipidemias:

vPresence of Hyperlipidemia is

strongest risk factor for

Atherosclerosis in persons younger

than 45 years of age.


vBoth primary and secondary

hyperlipidemia increases risk.

Dyslipidemias

directly associated with increased risk

of Atherosclerosis

? Elevated TAG (above reference range)
? Increased LDL (above reference range)
? Decreased HDL (Below reference range)
? Increased HDL (above reference range)
vHypertension

vHigh blood pressure produces

mechanical stress on vessel

endothelium.

vMajor risk factor for atherosclerosis in

al age groups

vMay be as important or more important

than hypercholesterolemia after age of

45 years.

vBlood Pressure >160 mmHg

increases risk for MI

?Regulation of Hypertension

may reduce risk of

Atherosclerosis.
vSubstances toxic to

endothelial cel s:

vHomocysteine
vC-Reactive Protein

Less Well Established Risk Factors

? High Serum Homocysteine Levels

? Homocysteine is derived from metabolism of dietary

Methionine

? Homocysteine inhibits elements of anticoagulant cascade

and is associated with endothelial damage.

? Infectious agents

? Presence of some organisms (Chlamydia pneumoniae,

herpesvirus hominis, cytomegalovirus) in atheromatous

lesions has been demonstrated by immunocytochemistry

? Organisms may play a role in atherosclerotic development

by initiating and enhancing inflammatory response.

? Elevated serum C-Reactive Protein

? It may increase likelihood of thrombus formation

? Inflammation marker
How An Atherosclerotic Plaque

Developed?

Common Arteries Atherosclerozied

?Aorta and its branches

?Coronary arteries

?Large vessels that supply

Brain

?Peripheral arteries
Pathogenesis Of Atherosclerosis

?Pathogenesis of

Atherosclerosis includes:

? Genetic Factors
? Environmental Factors

3 Stages of Atherosclerosis:

1.Initiation and Formation
2.Adaptation
3.Clinical
Development of Atherosclerosis

? Key event is damage to endothelium

? Damaged endothelium becomes

more permeable to Lipoproteins.

? Lipoproteins move below endothelial

layer (get lodged into intima).

? Damaged Endothelium looses its cel -

repel ent quality.

?Inflammatory cel s move into

vascular wal .

?Further Endothelial injury occurs by

attachment of leukocyte

(lymphocyte and monocyte) and

Platelet adherence

?Smooth muscle cel emigration and

proliferation
?Activated

macrophages

releases free radicals

that oxidizes LDL.

vLipid Engulfment by Macrophages

vOxidized LDL engulfed by

Macrophages transform to form

Foam cel s

vSubsequent development of an

atherosclerotic plaque with lipid

core



Effects Of Oxidized LDL
? Oxidized LDL is Toxic to Endothelium:

? Causes Endothelial loss

? Exposure of subendothelial tissue to blood

components

? Chemotactic effect

? Lymphocytes and Monocytes

? Smooth muscle cells from arterial media

? Stimulates production of Cytokines, adhesion

molecules in endothelium;

? Inhibits endothelium derived releasing factor

(EDRF), favoring vasospasm

? Stimulates specific immune system (production of

antibodies against oxidized LDL).

? Activated Macrophages also ingest

oxidized LDL to become foam cel s,


? Which are present in all stages of

atherosclerotic plaque formation.


? Lipids released from necrotic foam

cel s accumulate to form lipid core

of unstable plaques/Fatty streaks.
?Endothelial disruption

leads :

?Platelet adhesion and

aggregation


?Fibrin deposition

? Platelets and activated

macrophages release various

factors that are thought to

promote growth factors

? This modulate proliferation of

smooth muscle cells and

deposition of extracel ular

matrix in lesions: Elastin,

Col agen, Proteoglycans.


? Thus Connective tissue synthesis

and Calcium fixation

determinates stiffness of blood

vessels.

? Which causes further ulceration

of Atheromatous plaque.
Summary Of Pathogenesis Of

Atherosclerosis

? Accumulation of Lipids in vessel wal
? Plasma Lipoproteins
? Low-density lipoproteins LDL
? LDL transported inside macrophages to vessel

wal s

? Damage to Endothelium
? Adhesion of Macrophages
? Inflammation at the site

?Fatty Streaks
?Foam cells
?Smal Thrombi
?Calcification
? Plaque formation
?Ulceration
?Stiffening and Hardening

of blood vessels


Building Up of Atherosclerotic Plaque

Lesions Associated with

Atherosclerosis
? Lesions associated with Atherosclerosis are

of three types:

?Fatty streak
?Fibrous Atheromatous plaque
?Complicated Lesion

? Latter two are responsible for

clinical y significant manifestations

of disease.

? More advanced complicated

lesions are characterized by:

?Hemorrhage
?Ulceration
?Scar tissue deposits
? As a result of all pathogenic

mechanism

? Atherosclerosis can be defined

as vicious inflammatory process.

Modern Theory of Atherosclerosis
? Multifactor Theory:

?Structural and functional injury of vascular

endothelium

?Role of lipoproteins in initiation and

progression of lesions

?Response to injury of immune cel s and

smooth muscle cel s

?Role of growth factors and cytokines in

inflammation

?Role of repeated thrombosis in lesions

progression.

? Endothelial monolayer overlying an intima

contacts blood.

? Hypercholesterolemia promotes accumulation of LDL

particles (light spheres) in intima.

? Lipoprotein particles often associate with

constituents of the extracel ular matrix, notably

proteoglycans.

? Sequestration within intima separates lipoproteins

from some plasma antioxidants and favors oxidative

modification.

? Modified lipoprotein particles (darker spheres)

may trigger a local inflammatory response responsible

for subsequent steps in lesion formation.

? Increased expression of various adhesion

molecules for leukocytes recruits monocytes to the site

of a nascent arterial lesion.

? Once adherent, some white blood cel s wil migrate

into intima.
? Migration of leukocytes probably

depends on chemoattractant factors including modified

lipoprotein particles themselves and chemoattractant

cytokines depicted by the smal er spheres, produced by

vascular wal cel s in response to modified lipoproteins.

? Leukocytes in evolving fatty streak can divide and

exhibit increased expression of receptors for modified

lipoproteins (scavenger receptors).

? These mononuclear phagocytes ingest lipids and

become foam cel s, represented by a cytoplasm fil ed

with lipid droplets.

? As fatty streak evolves into a more complicated

atherosclerotic lesion, smooth-muscle cel s migrate

from media (bottom of lower panel), through

internal elastic membrane (solid wavy line), and

accumulate within expanding intima where they lay

down extracel ular matrix that forms the bulk of the

advanced lesion.

Consequences Of Atherosclerosis

OR

Effects/Complications

Of Atherosclerosis
? Atherosclerosis is a chronic

process

? Atherosclerosis affects almost

al people with variable

severity.

? Atherosclerosis develop over

several decades.

? If Congenital in origin It may

starts as early as infancy and

childhood,

? Progress very slowly during

life.
? Atherosclerosis contributes

to more mortality and


? More serious morbidity than

any other disorder in the

western world.

? Atherosclerosis affects the

intimal lining of endothelium

of

? Large and Medium-sized

elastic and muscular arteries

of body.
?Atherosclerotic plaque

formation

?Narrows diameter of

blood vessel lumen.

? Atherosclerosis leads to the

narrowing or complete blockage of

arteries /Occlusion by:

?Endothelial Dysfunction

?Lipid deposition

?Inflammatory reaction in vascular

wal

?Ulcerative Lesions
Atherosclerosis Brings Alterations Of Arteries :

? Aneurysm-Excessive localized swelling of

blood vessel

? Stenosis-Abnormal narrowing of vessel

? Occlusion-Closing of blood vessel

? Thrombosis-Local clotting of blood

? Embolism -blockage of vessel by lodging

of blood clot/fat globule

? Fissure-Small tear with bleeding

? Ulceration-Removal of top layer

? Calcification- Accumulation of Calcium

Salts

? Atherosclerosis , can and does, occur

in almost any artery in the body.

? Atherosclerosis of coronary arteries is

very crucial

? This blocks,blood circulation to Heart

? Which fails cardiac muscle to sustain.
? Atherosclerosis leads to disease

of cardiovascular system

affecting blood vessel wal .

? Causing Ischemic Heart Disease

which is leading cause of death

in developed countries.

Complications of

Atherosclerosis

? 1. Acute Occlusion:

Thrombosis

Occlusion

Ischemia, Infarction

? 2. Chronic Stenosis:

Chronic ischemia

Atrophy

Eg. Renal atrophy in renal artery stenosis, ischemic

atrophy of skin in DM
? 3. Aneurysm Formation:

Extension to media
Aneurysm
Aneurysmal rupture eg. Abdominal

aortic aneurysm

? 4. Embolism:

Of atherosclerotic plaque or of

thrombi

? Thrombosis is most important

complication of Atherosclerosis.

? It is caused by slowing and

turbulence of blood flow in region

of plaque and ulceration of plaque.
PHYSIOPATHOLOGICAL

CONSEQUENCES OF THE PLAQUE


v Coronary Artery Disease (CAD) : Angina, MI

v Cerebro Vascular Disease (CVD)

v Peripheral Artery Disease (PAD)

v Ischemic Stroke (Brain infarct)

v Secondary Erectile Disorder (ED)

v Chronic Renal Ischemia ( Renal failure)



? Atherosclerosis commonly

leads to:

?Myocardial infarction

?Stroke

?Gangrene of extremities
Biochemical Alterations

In Atherosclerosis

Biochemical Basis Of Atherosclerosis

? Low Blood supply to Cells/Tissues
? Low Nutrient and Oxygen Supply to cells
? Low Metabolism in cells
? Low Oxidative Phosphorylation
? Low ATP production in cells
? Low Cellular Activity
? Cellular/Tissue/Organ Dysfunction
? Irreversible Damage of cells/tissues/organ/system
Diagnosis Of Atherosclerosis

? Checking Lipid Profile/Lipoproteins
? B.P
? ECG
? Angiography
? EEG
? Color Doppler
? MRI
Management Of Atherosclerosis

? Reducing the risk factors
? Correcting the underlying causes
? Angioplasty
? Other Surgeries

Reduction Of Atherosclerosis Risk

Risk of atherosclerotic event can be

decreased by:

?Normal Balanced diet

?Physically active life

?Regular Exercise

?Smoking cessation

?Control of high blood pressure

?Intake of Antioxidants

?Drugs Statins, Ezetimibe


Development of Atherosclerosis

Process of Atherogenesis


Progression of CHD

Damage to

endothelium and

invasion of

macrophages

Smooth muscle

migration

Cholesterol

accumulates

around

macrophage and

muscle cel s

Collagen and

elastic fibers

form a matrix

around the

cholesterol,

macrophages

and muscle cel s

Pathogenesis of Coronary Heart Disease (CHD)
Monocyte Recruitment

LDL

lumen

intima

Plaque Rupture and Thrombosis

Tissue Factor

Platelet Aggregation

Lipid Core
NO Inactivation Due to Oxidative Stress

Sch?chinger V., Zeiher A.M.: Nephrol Dial Transplant (2002): 2055

Sch?chinger V., Zeiher A.M.: Nephrol Dial Transplant (2002): 2055


Process of Atherogenesis ? an overview


Formation of Atherosclerotic Plaques

lumen

neointima

Lipid Core

Plaque Build up in Artery


Overview of Artery




Cardio Vascular Disorders (CVD)

Coronary Artery Disease (CAD)

OR

Coronary Heart Disease(CHD)

OR

Ischemic Heart Disease(IHD)
Coronary Heart Disease

? Term Coronary Heart Disease

(CHD) describes Heart disease

caused by impaired coronary

blood flow.

? In most cases, it is caused by

Atherosclerosis of coronary

arteries which supply

Myocardium.

Clinical Manifestations
?Clinical manifestations of

Atherosclerosis depend on:

?Vessels involved

?Extent of vessel obstruction

? Atherosclerotic Lesions produce their

effects through:

?Narrowing of the blood vessel and

production of Ischemia;

?Sudden vessel obstruction caused by

Plaque hemorrhage or rupture;

?Thrombosis and formation of emboli

resulting from damage to the vessel

endothelium;
Coronary Artery Diseases Can cause:

?Angina/Chest Pain

?Myocardial Infarction /Heart attack

?Cardiac dysrhythmias

?Conduction defects

?Heart failure

?Sudden death

Myocardial Infarction


Myocardial Infarction

? MI is an irreversible damage

to Myocardium(Heart tissue)

? Acute myocardial infarction

(AMI), also known as a heart

attack
?AMI is caused due to

associated

Atherosclerotic disease

of the coronary arteries.

Risk Factors OF MI

Uncontrollable

Control able

?Sex

?High blood pressure
?High blood cholesterol

?Hereditary

?Smoking

?Race

?Physical activity
?Obesity

?Age

?Diabetes
?Stress and Anger












Screening and Diagnosis

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blood

sp

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Electro-

Stress

Coronary

ri
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cardiogram

Test

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Angiography

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to hear

ulses

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Narrowing in

Diagnosis Of MI

1. Pain

? Severe and Crushing,

? Constricting, Suffocating.

? Usual y is Sub Sternal, radiating to the left

arm, neck, or jaw

? Gastrointestinal Complaints

?Sensation of Epigastric distress

?Nausea and Vomiting
ECG

? Elevation of the ST segment

usually indicates acute myocardial

injury.


? When the ST segment is elevated

without associated Q waves, it is

called a Non?Q-wave Infarction.

Diagnostic Biochemical Markers Of MI

Enzymes and Proteins

? Lipid Profile

? CK ?MB

? AST

? LDH 1 and LDH2

? Trop T and Trop I

? Myoglobin

? Homocysteine

? hs CRP

? LP-PLA2
? Creatine kinase (CK), formerly called creatinine

phosphokinase, is an intracellular enzyme found

in muscle cells. Muscles, including cardiac

muscle, use ATP as their energy source.

? Creatine Phosphate, which serves as a storage

form of energy in muscle, uses CK to convert

ADP to ATP.

? CK exceeds normal range within 4 to 8 hours of

myocardial injury and declines to normal within

2 to 3 days.

? There are three isoenzymes of CK, with the MB

isoenzyme (CK-MB) being highly specific for

injury to myocardial tissue.

? Myoglobin is an Oxygen-Storing Protein, that is

normally present in cardiac and skeletal muscle.

? It is a small molecule that is released quickly from

infarcted myocardial tissue and becomes

elevated within 1 hour after myocardial cell

death, with peak levels reached within 4 to 8

hours.

? It rapidly eliminates through urine (low

molecular weight).

? Because myoglobin is present in both cardiac and

skeletal muscle, it is not cardiac specific.
? Troponin complex consists of three subunits

? Troponin C

? Troponin I

? Troponin T

? These subunits are released during myocardial

infarction.

? Cardiac muscle forms of both Troponin T and

Troponin I are used in diagnosis of myocardial

infarction.

? High sensitive Cardiac Troponin I is current

Biomarker validation in research of early

diagnosis of AMI

? Troponin I (and Troponin T) rises more

slowly than myoglobin

? This may be useful for diagnosis of

infarction, even up to 3 to 4 days after the

event.

? It is thought that cardiac Troponin assays

are more capable of detecting episodes of

myocardial infarction in which cel damage

is below that detected by CK-MB level.
Effects of Acute Myocardial

Infarction (AMI)

? The principal biochemical

consequence of AMI is

? The conversion from aerobic to

anaerobic metabolism

? With inadequate production of

energy(ATP) to sustain normal

Myocardial function.

? Ischemic area ceases to

function within a matter of

minutes, and

? Irreversible Myocardial cell

damage occurs after 20 to 40

minutes of severe ischemia.
Treatment

? Reperfusion

? (Re-establishment of blood flow)
? Thrombolytic therapy

?Streptokinase/ Urokinase

? Revascularization procedures


?Early Reperfusion (within 15 to

20 minutes) after onset of

ischemia can prevent necrosis.

?Reperfusion after a longer

interval can salvage some of the

myocardial cells that would have

died because of longer periods of

ischemia.

Treatment 1) Stenting

? A Stent (narrow expandable tube) is introduced into a blood vessel on

a bal oon catheter and advanced into the blocked area of the artery
? The bal oon is then inflated and causes the stent to expand until it fits

the inner wal of the vessel, conforming to contours as needed
? The bal oon is then deflated and drawn back
?The stent stays in place permanently, holding the vessel open and

improving the flow of blood.






Treatment 2) Angioplasty

?Bal oon catheter is passed through the guiding catheter to the area

near the narrowing. A guide wire inside the balloon catheter is then

advanced through the artery until the tip is beyond the narrowing.
? The angioplasty catheter is moved over the guide wire until the

balloon is within the narrowed segment.
? Balloon is inflated, compressing the plaque against the artery wall
? Once plaque has been compressed and the artery has been

sufficiently opened, the balloon catheter will be deflated and removed.


Treatment

3) Bypass surgery

? healthy blood vessel is removed from leg, arm or chest
? blood vessel is used to create new blood flow path in your heart
? the "bypass graft" enables blood to reach your heart by flowing

around (bypassing)

the blocked portion of

the diseased artery.

The increased blood

flow reduces angina

and the risk of heart

attack.

Peripheral Arterial Disease (PAD)
Peripheral Arterial Disease (PAD)

? PAD refers to the obstruction of

large arteries in lower extremities

of leg

? It possess, inflammatory

processes leading to stenosis, an

embolism, or thrombus formation.

Risk of PAD

? Risk of PAD also increases in

individuals who are:

?Over the age of 50
?Male Obese
?With a family history of vascular

disease, heart attack, or stroke.
Symptoms OF PAD

? About 20% of patients with mild PAD may be

asymptomatic;

? Symptoms of PAD include:

? Pain, weakness, numbness, or cramping in muscles

due to decreased blood flow

? Sores, wounds, or ulcers that heal slowly or not at all

? Noticeable change in color (blueness or paleness) or

temperature (coolness) when compared to the other

limb

? Diminished hair and nail growth on affected limb and

digits.
Prevention Of Dyslipidemias

And Its

Consequences And Complications

Live Sensible Implement

?Get regular medical checkups
?Eat a Heart-Balanced healthy diet
?Control your blood pressure
?Check your Blood Cholesterol
?Don't smoke and drink Alcohol
?Exercise regularly
?Maintain a healthy weight
?Manage stress


THE HEALTHY PLATE



FOODS THAT LOWER LDL

CHOLESTEROL

1. Oats

2. Barley and Whole grains

3. Beans

4. Eggplant and okra

5. Nuts

6. Vegetable oils (canola, sunflower, safflower)

7. Apples, grapes, strawberries, citrus fruits

8. Soy

9. Fatty Fish

10. Fiber supplements
qEat meat sparingly

qAdd Fish to your diet

qGo for Nuts

qEat Fruits and Vegetables

qIncrease Complex Carbohydrates and fiber

qOpt for low-Fat dairy products

qCut down on Saturated fat in cooking

qAvoid Palm and Coconut oils ( Rich in SFAs)

qAvoid Trans Fats

qReduce Dietary Cholesterol

qReduce Salt intake

qWatch the Snacks

Blood Cholesterol levels increase

by eating these products

? Refined Sugars
? Beef
? Poultry
? Fish
? Milk
? Eggs
? Cheese
? Yogurt
EXERCISE



qAerobic exercise (jogging, swimming, brisk walking,

bicycling, etc)

STRESS REDUCTION STEPS

? Be Spiritual

? Balance All Actions

? Make and Fol ow Right protocols

? Be Planned and Organized

? Manage works based on priority

? Involve In work which you are chosen for

? Be Obedient and Have Patience

? Be Happy with what get

? Not expect too much in life

? Repent, Accept But Do Not Repeat

? Ventilate And Communicate


Summary To Prevent

? Eat right

? Watch your weight -even a modest drop in

weight can make a difference

? Be Active - start a program of light exercise

for at least 30-45 minutes every day

? Lower your stress levels. Practice stress

reduction techniques

? Stop smoking and drinking alcohol

? Be Spiritual

Avoid

Promote

Unhealthy eating

Healthy eating




Visit your doctor

Relaxation

regularly

Check your weight

Balance intake with output

Exercise regularly

Inborn Errors Of Lipid Metabolism
Inborn Error Of Enzyme

Abnormal

Lipid

Deficient/

Accumulation

Metabolism

Defect

Of

Sudden Infant

Acyl CoA

Acyl CoAs

Death Syndrome

Dehydrogenase

(SIDS)

Refsums Disease

-Phytanic Acid Phytanic Acid

Oxidase

Zellwegers

Peroxisomal

VLCFAs in

Syndrome

Oxidation

Peroxisomes

Inborn Error

Enzyme Defect

Abnormal

Lipid Storage

Accumulation Of

Disorders

Niemann Picks

Sphingomyelinase Sphingomyelin in

Disease

Liver and Spleen

Tay Sachs Disease Hexoseaminidase Gangliosides in

Defect

Tissues

Gaucher's Disease eta Glucosidase Glucosides in Tissues
Inborn Enzyme

Abnormal

Error

Defect

Accumulation Of

Krabbe's Beta

Disease Galactosidase Galactocerebroside

Farbers Ceramidase

Ceramides

Disease


Role Of Insulin In Lipid Metabolism

? Insulin

? Stimulates LPL

? increased uptake of FA

from Chylomicrons and

VLDL

? Stimulates Glycolysis

? increased glycerol

phosphate synthesis

? increases esterification

? Induces HSL-phosphatase

? inactivates HSL

? Inhibits Lipolysis

? Net effect: TG storage

? Lack of Insulin

?Free Fatty acids build up in

blood

?Can lead to excess Acetoacetic

acid production and buildup of

acetone (acidosis, which can

lead to blindness and coma)
Insulin

Most Cel s

amino

Control

Protein synthesis

acids

Muscle

Glucose uptake

Glycogen synthesis

Gastrointestinal

hormones

triglycerides

Adipose

Glucose uptake

Glycerol production

Triglyceride breakdown

Amino

Pancreas Insulin

Triglyceride synthesis

acids

Beta cells

Liver

Blood

Glucose uptake

glucose

glucose

Glycogen synthesis

Fatty acid synthesis

Glucose synthesis

Brain

No effect

Feedback

Glucagon

Control

Adipose

Triglyceride breakdown

Fatty acids

? Triglyceride storage

Exercise

Amino acids

Pancreas

Alpha cells

Liver

Glycogen breakdown

Glucose synthesis

Blood glucose

Epinephrine

Glucose release

(stress)

Brain

No effect


Types Of Lipases
S.

Type Of Lipase

Location

No

Action Upon

1

Lingual Lipase

Mouth

Dietary TAG

(Insignificant Action)

2

Gastric Lipase

Stomach

Dietary TAG

(Insignificant Action)

3

Pancreatic Lipase

Smal Intestine

Dietary TAG

(Significant Action)

S. Type Of Lipase

Location

No

Action

4

Lipoprotein Lipase

Endothelial Lining

Of Blood Vessels

Lipoprotein TAG

5

Hormone Sensitive

Adiposecytes

Lipase

Hydrolyzes

Stored TAG

6

Hepatic Lipase

Liver

TAG

7

Phopshpholipase A2 Small Intestine

Phospholipids
Questions

Q.1. Describe in details the digestion

& absorption of dietary form of lipids

& add a note on Steatorrhoea


OR

Q.1.What are different forms of

dietary lipids? How the dietary lipids

are digested & absorbed in G.I.T ?
Q.2. What are the different modes of oxidation of

fatty acids in the body? Give -oxidation of even

chain fatty acid.

OR

Q.2. Define -oxidation of fatty acid. Explain the

oxidation of Palmitate and calculate its

energetics./Fate of fatty acids in human body?

OR

Q.2. Explain -oxidation of odd chain fatty acids.

Q.3. What is Lipogenesis? Describe in

details the De-novo synthesis of fatty

acid.

OR

Q.3. Explain the Extra mitochondrial

synthesis of Palmitate.
Q.4. What is ketoacidosis? Give fate &

formation ketone bodies.
? Short Notes

? Transport & storage of lipids / Role

lipoproteins.

? Emulsification & its significance / Role of

Bile salts in digestion & absorption of lipid.

? Lipolysis / Role of Hormone Sensitive

Lipase/Adipose tissue metabolism.

? Clearing factor / Lipoprotein

lipase.

? Multi-enzyme complex of Fatty

acid biosynthesis / Fatty acid

synthesis complex.

? Microsomal synthesis of fatty acid.
? Fatty liver /Lipotropic factors.
? Cholesterol-outline of Biosynthesis.

? Hypercholesterolemia ? causes &

consequences

? Atherosclerosis

? Myocardial Infarction

? Enumerate the Inborn errors related to

lipid metabolism.

? Transport & Excretion of Cholesterol/

Reverse transport of cholesterol.

? Fate & formation of Acetyl?CoA
? Fate of Propionyl-CoA
? Role of Carnitine in Lipid metabolism
? Role of Liver in Lipid metabolism.
? TAG metabolism.
? Ketonemia & Ketonuria
? Represent the schematic structure of

lipoprotein.

? Role of Citrate in lipid metabolism.
? Role of Carnitine in lipid metabolism.
? Hormonal Influence in Lipid

Metabolism

? Catabolism of Cholesterol.
? CETP activity
? HDL2 and HDL 3
? Zellweger & Refsum's disease.
? Mixed Micelle
? Four types of Lipoproteins & their role
? Hyperlipoproteinemias
? Hypolipoproteinemia's
? Different types of Lipases & their action.
Biochemistry Department

This post was last modified on 05 April 2022