Download MBBS (Bachelor of Medicine, Bachelor of Surgery) 1st year (First Year) Biochemistry ppt lectures Topic 74 Atherosclerosis Lipid Disorders Notes. - biochemistry notes pdf, biochemistry mbbs 1st year notes pdf, biochemistry mbbs notes pdf, biochemistry lecture notes, paramedical biochemistry notes, medical biochemistry pdf, biochemistry lecture notes 2022 ppt, biochemistry pdf.
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
me
mea
a
s
s
u
sh
u
re
ows
r
s
es
fic
eci
s
e
blood
sp
rical
Electro-
Stress
Coronary
ri
a
n
ect
cardiogram
Test
t
S
Angiography
ro
el
i
o
te
c
s o
su
f
p
to hear
ulses
ply
imp
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