SlideShare a Scribd company logo
Cholesterol Metabolism
Cardiovascular Block
Overview
• Introduction
• Cholesterol structure
• Cholesteryl esters
• Cholesterol synthesis
• Rate limiting step
• Regulation of cholesterol synthesis
• Regulation of HMG CoA reductase
• Excretion of cholesterol
• Hypercholesterolemia and treatment
Cholesterol
• Most important animal steroid
• Maintains membrane fluidity
• Insulating effect on nerve fibres
• Cholesterol is the parent molecule for
– Bile acids and bile salts
– Steroid hormones
– Vitamin D3
Liver plays a central role in
the regulation of
cholesterol homeostasis
Cholesterol Structure
Cholesteryl esters
• Most plasma cholesterol is esterified with a
fatty acid
• CEs are not present in membranes
• Present in small amounts in most cells
• More hydrophobic than cholesterol
Cholesterol synthesis
• Synthesized in all tissues
• Major sites for synthesis: liver, adrenal cortex,
testes, ovaries and intestine
• All carbon atoms are derived from acetyl CoA
• Enzymes involved in biosynthesis are partly
located in ER and partly in cytoplasm
Synthesis of HMG CoA
• HMG CoA is present in
both cytosol and
mitochondria of liver
• Mitochondrial-
ketogenesis
• Cytosolic – cholesterol
synthesis
Synthesis of mevalonic acid
• Rate limiting and key
step
• Occurs in cytosol
• HMG CoA reductase is
an ER membrane
enzyme with catalytic
unit hanging in the
cytosol
Further steps in synthesis
• Production of a 5-carbon unit:
– Isopentinyl pyrophosphate (IPP)
• Condensation to a 30C compound: squalene
• Cyclization of squalene to 30C lanosterol
• Synthesis of 27-Carbon cholesterol (defect in
this leads to Smith-Lemli-Opitz Syndrome)
Regulation of Cholesterol Synthesis
• HMG CoA reductase is the rate-limiting enzyme
of cholesterol synthesis
HMG CoA Reductase Regulation
Gene
Transcription
Translation
HMG CoA Reductase
HMG CoA
Cholesterol
Cholesterol
Glucagon
Cortisones
Statins
Insulin
Thyroxin
HMG CoA Reductase Regulation
• Sterol-dependent regulation of gene
expression
• Sterol-accelerated enzyme degradation
• Sterol-independent
phosphorylation/dephosphorylation
• Hormonal regulation
Sterol-dependent regulation of gene
expression of HMG CoA
• When sufficient cholesterol is present,
transcription is suppressed and vice versa
• Sterol Regulatory Element (SRE) is a recognition
sequence in the DNA
• SREBP (SRE binding protein) binding to SRE is
essential for transcription of this gene
• SREBP cleavage-activating protein (SCAP) is an
intracellular cholesterol sensor
Sterol-dependent regulation
Cholesterol High
• SCAP binds to insig protein
(insulin-induced protein) in
ER membrabe
• SCAP-SREBP is retained in the
ER
• Down regulation of
cholesterol synthesis
Cholesterol Low
• SCAP-SREBP moves to Golgi
bodies
• SCAP is removed from SREBP
• SREBP binds to SRE in DNA
• HMG CoA gene is activated
Enzyme phosphorylation and
dephosphorylation
• AMP- activated protein kinase (AMPK) for
phosphorylation
• Phosphorylated form of enzyme is inactive
• Dephosphorylated form is active
• Low ATP or High AMP  cholesterol
synthesis decreases
Hormonal Regulation
• Insulin and thyroxine increase upregulation of
enzyme expression
• Glucagon and cortisol have opposite effect
Excretion of cholesterol
• By conversion into bile acids and bile salts-
excreted in the feces
– Secretion of cholesterol in bile
– Transported to intestine for elimination
• In the intestine, some cholesterol is converted
by bacteria into coprostanol and cholestanol
before excretion
Hypercholesterolemia
• High conc. of cholesterol in blood
• Leads to atherosclerosis
• Statin drugs are used to decrease plasma
cholesterol levels
• Statins are structural analogs of HMG CoA
reductase
• Statins inhibit enzyme activity by competitive
inhibition
β-Sitosterols/ Phytosterols
• Plant sterols and are poorly absorbed by
humans
• Block the absorption of dietary cholesterol
• Clinically useful in the dietary treatment of
hypercholesterolemia

More Related Content

What's hot

CL- 03: Compound lipids-(Phospholipids)
CL- 03: Compound lipids-(Phospholipids)CL- 03: Compound lipids-(Phospholipids)
CL- 03: Compound lipids-(Phospholipids)
Dr. Santhosh Kumar. N
 
Metabolism of phospholipids
Metabolism of phospholipidsMetabolism of phospholipids
Metabolism of phospholipids
Ramesh Gupta
 
Glycolysis
GlycolysisGlycolysis
Glycolysis
Muhammed sadiq
 
Eicosanoids
EicosanoidsEicosanoids
Eicosanoids
Supta Sarkar
 
Biosynthesis of phospholipids
Biosynthesis of phospholipidsBiosynthesis of phospholipids
Biosynthesis of phospholipids
Nusrat Sheikh
 
Glycogen metabolism
Glycogen metabolismGlycogen metabolism
4.2 glycolysis & TCA cycle.ppt
4.2 glycolysis & TCA cycle.ppt4.2 glycolysis & TCA cycle.ppt
4.2 glycolysis & TCA cycle.ppt
Dr. Neelam H. Zaidi
 
Lipid metabolism
Lipid metabolismLipid metabolism
Lipid metabolism
Oheneba Hagan
 
Metabolism of Lipids
Metabolism of Lipids Metabolism of Lipids
Metabolism of Lipids
ANKUSH GOYAL
 
Glycolysis
GlycolysisGlycolysis
Glycolysis
Pawan Kumar
 
Heme synthesis
Heme synthesisHeme synthesis
2011 lipids i (1)
2011 lipids i (1)2011 lipids i (1)
2011 lipids i (1)MUBOSScz
 
Lipid metabolism
Lipid metabolismLipid metabolism
Lipid metabolism
Dipali Kulkarni
 
Fructose metabolism
Fructose metabolismFructose metabolism
Fructose metabolism
Dr. Khuram Aziz
 
Lipoproteins: Structure, classification, metabolism and significance
Lipoproteins:  Structure, classification, metabolism and significanceLipoproteins:  Structure, classification, metabolism and significance
Lipoproteins: Structure, classification, metabolism and significance
enamifat
 
Glycogen metabolism and it’s regulation
Glycogen metabolism and it’s regulationGlycogen metabolism and it’s regulation
Glycogen metabolism and it’s regulation
BiochemistrySGRDIMSAR
 
HM-02 Heme catabolism & Genetic defects.pptx
HM-02 Heme catabolism & Genetic defects.pptxHM-02 Heme catabolism & Genetic defects.pptx
HM-02 Heme catabolism & Genetic defects.pptx
Dr. Santhosh Kumar. N
 
Biological oxidation and etc
Biological oxidation and etcBiological oxidation and etc
Biological oxidation and etc
Nidhi Argade
 

What's hot (20)

CL- 03: Compound lipids-(Phospholipids)
CL- 03: Compound lipids-(Phospholipids)CL- 03: Compound lipids-(Phospholipids)
CL- 03: Compound lipids-(Phospholipids)
 
hmp-shunt
 hmp-shunt hmp-shunt
hmp-shunt
 
Metabolism of phospholipids
Metabolism of phospholipidsMetabolism of phospholipids
Metabolism of phospholipids
 
Cholesterol metabolism
Cholesterol metabolismCholesterol metabolism
Cholesterol metabolism
 
Glycolysis
GlycolysisGlycolysis
Glycolysis
 
Eicosanoids
EicosanoidsEicosanoids
Eicosanoids
 
Biosynthesis of phospholipids
Biosynthesis of phospholipidsBiosynthesis of phospholipids
Biosynthesis of phospholipids
 
Glycogen metabolism
Glycogen metabolismGlycogen metabolism
Glycogen metabolism
 
4.2 glycolysis & TCA cycle.ppt
4.2 glycolysis & TCA cycle.ppt4.2 glycolysis & TCA cycle.ppt
4.2 glycolysis & TCA cycle.ppt
 
Lipid metabolism
Lipid metabolismLipid metabolism
Lipid metabolism
 
Metabolism of Lipids
Metabolism of Lipids Metabolism of Lipids
Metabolism of Lipids
 
Glycolysis
GlycolysisGlycolysis
Glycolysis
 
Heme synthesis
Heme synthesisHeme synthesis
Heme synthesis
 
2011 lipids i (1)
2011 lipids i (1)2011 lipids i (1)
2011 lipids i (1)
 
Lipid metabolism
Lipid metabolismLipid metabolism
Lipid metabolism
 
Fructose metabolism
Fructose metabolismFructose metabolism
Fructose metabolism
 
Lipoproteins: Structure, classification, metabolism and significance
Lipoproteins:  Structure, classification, metabolism and significanceLipoproteins:  Structure, classification, metabolism and significance
Lipoproteins: Structure, classification, metabolism and significance
 
Glycogen metabolism and it’s regulation
Glycogen metabolism and it’s regulationGlycogen metabolism and it’s regulation
Glycogen metabolism and it’s regulation
 
HM-02 Heme catabolism & Genetic defects.pptx
HM-02 Heme catabolism & Genetic defects.pptxHM-02 Heme catabolism & Genetic defects.pptx
HM-02 Heme catabolism & Genetic defects.pptx
 
Biological oxidation and etc
Biological oxidation and etcBiological oxidation and etc
Biological oxidation and etc
 

Similar to Amer cholesterol metabolism

2- Cholesterol Metabolism __.ppt
2- Cholesterol Metabolism __.ppt2- Cholesterol Metabolism __.ppt
2- Cholesterol Metabolism __.ppt
reem867991
 
2- Cholesterol Metabolism __.ppt
2- Cholesterol Metabolism __.ppt2- Cholesterol Metabolism __.ppt
2- Cholesterol Metabolism __.ppt
El Saadany Mohamad
 
Cholesterol metabolism 2
Cholesterol metabolism 2Cholesterol metabolism 2
Cholesterol metabolism 2
Bishal Chauhan
 
Lecture-SUNDAY Cholesterol-Metabolism.pptx
Lecture-SUNDAY Cholesterol-Metabolism.pptxLecture-SUNDAY Cholesterol-Metabolism.pptx
Lecture-SUNDAY Cholesterol-Metabolism.pptx
sukayna2
 
Cholesterol
CholesterolCholesterol
Cholesterol
KAVIN6369950450
 
Biosynthesis of cholesterol
Biosynthesis of cholesterolBiosynthesis of cholesterol
Biosynthesis of cholesterol
madhu_mathi
 
Adrenal gland physiology
Adrenal gland physiologyAdrenal gland physiology
Adrenal gland physiology
eleku2
 
Cholesterol for classs
Cholesterol for classsCholesterol for classs
Cholesterol for classs
Hari Sharan Makaju
 
Cholesterol synthesis and breakdown
Cholesterol synthesis and breakdownCholesterol synthesis and breakdown
Cholesterol synthesis and breakdown
Amer
 
Cholesterol synthesis,transport and excretion
Cholesterol synthesis,transport and excretionCholesterol synthesis,transport and excretion
Cholesterol synthesis,transport and excretion
apeksha40
 
adrenocorticalhormones-150813193623-lva1-app6892 (1).pdf
adrenocorticalhormones-150813193623-lva1-app6892 (1).pdfadrenocorticalhormones-150813193623-lva1-app6892 (1).pdf
adrenocorticalhormones-150813193623-lva1-app6892 (1).pdf
MuhammadAmmaz
 
Adrenocortical hormones
Adrenocortical hormonesAdrenocortical hormones
Adrenocortical hormones
Lubna Abu Alrub,DDS
 
1 handout biokimia lanjut. p.ukun
1 handout biokimia lanjut. p.ukun1 handout biokimia lanjut. p.ukun
1 handout biokimia lanjut. p.ukun
agakayaraya
 
Cholesterol Biosyn 2- best.ppt
Cholesterol Biosyn 2- best.pptCholesterol Biosyn 2- best.ppt
Cholesterol Biosyn 2- best.ppt
KomeriClevis
 
Group G biochem.pptx
Group G biochem.pptxGroup G biochem.pptx
Group G biochem.pptx
santiagobutcher
 
CHOLESTEROL | CHOLESTEROL METABOLISM | CHOLESTEROL BIOSYNTHESIS
CHOLESTEROL | CHOLESTEROL METABOLISM | CHOLESTEROL BIOSYNTHESISCHOLESTEROL | CHOLESTEROL METABOLISM | CHOLESTEROL BIOSYNTHESIS
CHOLESTEROL | CHOLESTEROL METABOLISM | CHOLESTEROL BIOSYNTHESIS
kiransharma204
 
Lec11 lipid met
Lec11 lipid metLec11 lipid met
Lec11 lipid metdream10f
 
CHOLESTEROL BIOSYNTHESIS
CHOLESTEROL BIOSYNTHESISCHOLESTEROL BIOSYNTHESIS
CHOLESTEROL BIOSYNTHESIS
YESANNA
 
Cholesterol Biosynthesis and catabolism for MBBS, Lab. MEd. BDS.pptx
Cholesterol Biosynthesis  and catabolism for MBBS, Lab. MEd. BDS.pptxCholesterol Biosynthesis  and catabolism for MBBS, Lab. MEd. BDS.pptx
Cholesterol Biosynthesis and catabolism for MBBS, Lab. MEd. BDS.pptx
Rajendra Dev Bhatt
 
Steroids and Cholesterol
Steroids and CholesterolSteroids and Cholesterol
Steroids and Cholesterol
W-Z Presenters
 

Similar to Amer cholesterol metabolism (20)

2- Cholesterol Metabolism __.ppt
2- Cholesterol Metabolism __.ppt2- Cholesterol Metabolism __.ppt
2- Cholesterol Metabolism __.ppt
 
2- Cholesterol Metabolism __.ppt
2- Cholesterol Metabolism __.ppt2- Cholesterol Metabolism __.ppt
2- Cholesterol Metabolism __.ppt
 
Cholesterol metabolism 2
Cholesterol metabolism 2Cholesterol metabolism 2
Cholesterol metabolism 2
 
Lecture-SUNDAY Cholesterol-Metabolism.pptx
Lecture-SUNDAY Cholesterol-Metabolism.pptxLecture-SUNDAY Cholesterol-Metabolism.pptx
Lecture-SUNDAY Cholesterol-Metabolism.pptx
 
Cholesterol
CholesterolCholesterol
Cholesterol
 
Biosynthesis of cholesterol
Biosynthesis of cholesterolBiosynthesis of cholesterol
Biosynthesis of cholesterol
 
Adrenal gland physiology
Adrenal gland physiologyAdrenal gland physiology
Adrenal gland physiology
 
Cholesterol for classs
Cholesterol for classsCholesterol for classs
Cholesterol for classs
 
Cholesterol synthesis and breakdown
Cholesterol synthesis and breakdownCholesterol synthesis and breakdown
Cholesterol synthesis and breakdown
 
Cholesterol synthesis,transport and excretion
Cholesterol synthesis,transport and excretionCholesterol synthesis,transport and excretion
Cholesterol synthesis,transport and excretion
 
adrenocorticalhormones-150813193623-lva1-app6892 (1).pdf
adrenocorticalhormones-150813193623-lva1-app6892 (1).pdfadrenocorticalhormones-150813193623-lva1-app6892 (1).pdf
adrenocorticalhormones-150813193623-lva1-app6892 (1).pdf
 
Adrenocortical hormones
Adrenocortical hormonesAdrenocortical hormones
Adrenocortical hormones
 
1 handout biokimia lanjut. p.ukun
1 handout biokimia lanjut. p.ukun1 handout biokimia lanjut. p.ukun
1 handout biokimia lanjut. p.ukun
 
Cholesterol Biosyn 2- best.ppt
Cholesterol Biosyn 2- best.pptCholesterol Biosyn 2- best.ppt
Cholesterol Biosyn 2- best.ppt
 
Group G biochem.pptx
Group G biochem.pptxGroup G biochem.pptx
Group G biochem.pptx
 
CHOLESTEROL | CHOLESTEROL METABOLISM | CHOLESTEROL BIOSYNTHESIS
CHOLESTEROL | CHOLESTEROL METABOLISM | CHOLESTEROL BIOSYNTHESISCHOLESTEROL | CHOLESTEROL METABOLISM | CHOLESTEROL BIOSYNTHESIS
CHOLESTEROL | CHOLESTEROL METABOLISM | CHOLESTEROL BIOSYNTHESIS
 
Lec11 lipid met
Lec11 lipid metLec11 lipid met
Lec11 lipid met
 
CHOLESTEROL BIOSYNTHESIS
CHOLESTEROL BIOSYNTHESISCHOLESTEROL BIOSYNTHESIS
CHOLESTEROL BIOSYNTHESIS
 
Cholesterol Biosynthesis and catabolism for MBBS, Lab. MEd. BDS.pptx
Cholesterol Biosynthesis  and catabolism for MBBS, Lab. MEd. BDS.pptxCholesterol Biosynthesis  and catabolism for MBBS, Lab. MEd. BDS.pptx
Cholesterol Biosynthesis and catabolism for MBBS, Lab. MEd. BDS.pptx
 
Steroids and Cholesterol
Steroids and CholesterolSteroids and Cholesterol
Steroids and Cholesterol
 

More from Amer

LARYNX.pptx
LARYNX.pptxLARYNX.pptx
LARYNX.pptx
Amer
 
Liver Tests
Liver TestsLiver Tests
Liver Tests
Amer
 
glucagon disorder
glucagon disorder glucagon disorder
glucagon disorder
Amer
 
Amer cerrhosis of liver
Amer cerrhosis of liverAmer cerrhosis of liver
Amer cerrhosis of liver
Amer
 
Amer glycogen storage disease
Amer glycogen storage diseaseAmer glycogen storage disease
Amer glycogen storage disease
Amer
 
Amer cholesterol syn
Amer cholesterol synAmer cholesterol syn
Amer cholesterol syn
Amer
 
3 evaluation and management of rheumatoid arthritis
3 evaluation and management of rheumatoid arthritis3 evaluation and management of rheumatoid arthritis
3 evaluation and management of rheumatoid arthritis
Amer
 
Arthritis
ArthritisArthritis
Arthritis
Amer
 
Final rheumatoid arthritis
Final rheumatoid arthritisFinal rheumatoid arthritis
Final rheumatoid arthritis
Amer
 
Final rheumatoid arthritis
Final rheumatoid arthritisFinal rheumatoid arthritis
Final rheumatoid arthritis
Amer
 
Rheumatic diseases
Rheumatic diseasesRheumatic diseases
Rheumatic diseases
Amer
 
Rheumatoid arthritis
Rheumatoid arthritisRheumatoid arthritis
Rheumatoid arthritis
Amer
 
Cerebral circulation
Cerebral circulationCerebral circulation
Cerebral circulation
Amer
 
Radioactive application in medical
Radioactive application in medicalRadioactive application in medical
Radioactive application in medical
Amer
 
Endoscopy and types of endoscopy
Endoscopy and types of endoscopy Endoscopy and types of endoscopy
Endoscopy and types of endoscopy
Amer
 
Developing writing
Developing writingDeveloping writing
Developing writing
Amer
 
Kingdom of fungi
Kingdom of fungiKingdom of fungi
Kingdom of fungi
Amer
 
Dna
DnaDna
Dna
Amer
 

More from Amer (18)

LARYNX.pptx
LARYNX.pptxLARYNX.pptx
LARYNX.pptx
 
Liver Tests
Liver TestsLiver Tests
Liver Tests
 
glucagon disorder
glucagon disorder glucagon disorder
glucagon disorder
 
Amer cerrhosis of liver
Amer cerrhosis of liverAmer cerrhosis of liver
Amer cerrhosis of liver
 
Amer glycogen storage disease
Amer glycogen storage diseaseAmer glycogen storage disease
Amer glycogen storage disease
 
Amer cholesterol syn
Amer cholesterol synAmer cholesterol syn
Amer cholesterol syn
 
3 evaluation and management of rheumatoid arthritis
3 evaluation and management of rheumatoid arthritis3 evaluation and management of rheumatoid arthritis
3 evaluation and management of rheumatoid arthritis
 
Arthritis
ArthritisArthritis
Arthritis
 
Final rheumatoid arthritis
Final rheumatoid arthritisFinal rheumatoid arthritis
Final rheumatoid arthritis
 
Final rheumatoid arthritis
Final rheumatoid arthritisFinal rheumatoid arthritis
Final rheumatoid arthritis
 
Rheumatic diseases
Rheumatic diseasesRheumatic diseases
Rheumatic diseases
 
Rheumatoid arthritis
Rheumatoid arthritisRheumatoid arthritis
Rheumatoid arthritis
 
Cerebral circulation
Cerebral circulationCerebral circulation
Cerebral circulation
 
Radioactive application in medical
Radioactive application in medicalRadioactive application in medical
Radioactive application in medical
 
Endoscopy and types of endoscopy
Endoscopy and types of endoscopy Endoscopy and types of endoscopy
Endoscopy and types of endoscopy
 
Developing writing
Developing writingDeveloping writing
Developing writing
 
Kingdom of fungi
Kingdom of fungiKingdom of fungi
Kingdom of fungi
 
Dna
DnaDna
Dna
 

Recently uploaded

Novas diretrizes da OMS para os cuidados perinatais de mais qualidade
Novas diretrizes da OMS para os cuidados perinatais de mais qualidadeNovas diretrizes da OMS para os cuidados perinatais de mais qualidade
Novas diretrizes da OMS para os cuidados perinatais de mais qualidade
Prof. Marcus Renato de Carvalho
 
ANATOMY AND PHYSIOLOGY OF URINARY SYSTEM.pptx
ANATOMY AND PHYSIOLOGY OF URINARY SYSTEM.pptxANATOMY AND PHYSIOLOGY OF URINARY SYSTEM.pptx
ANATOMY AND PHYSIOLOGY OF URINARY SYSTEM.pptx
Swetaba Besh
 
Physiology of Chemical Sensation of smell.pdf
Physiology of Chemical Sensation of smell.pdfPhysiology of Chemical Sensation of smell.pdf
Physiology of Chemical Sensation of smell.pdf
MedicoseAcademics
 
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?Report Back from SGO 2024: What’s the Latest in Cervical Cancer?
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?
bkling
 
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...
i3 Health
 
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...
VarunMahajani
 
Physiology of Special Chemical Sensation of Taste
Physiology of Special Chemical Sensation of TastePhysiology of Special Chemical Sensation of Taste
Physiology of Special Chemical Sensation of Taste
MedicoseAcademics
 
KDIGO 2024 guidelines for diabetologists
KDIGO 2024 guidelines for diabetologistsKDIGO 2024 guidelines for diabetologists
KDIGO 2024 guidelines for diabetologists
د.محمود نجيب
 
basicmodesofventilation2022-220313203758.pdf
basicmodesofventilation2022-220313203758.pdfbasicmodesofventilation2022-220313203758.pdf
basicmodesofventilation2022-220313203758.pdf
aljamhori teaching hospital
 
Ocular injury ppt Upendra pal optometrist upums saifai etawah
Ocular injury  ppt  Upendra pal  optometrist upums saifai etawahOcular injury  ppt  Upendra pal  optometrist upums saifai etawah
Ocular injury ppt Upendra pal optometrist upums saifai etawah
pal078100
 
Knee anatomy and clinical tests 2024.pdf
Knee anatomy and clinical tests 2024.pdfKnee anatomy and clinical tests 2024.pdf
Knee anatomy and clinical tests 2024.pdf
vimalpl1234
 
How STIs Influence the Development of Pelvic Inflammatory Disease.pptx
How STIs Influence the Development of Pelvic Inflammatory Disease.pptxHow STIs Influence the Development of Pelvic Inflammatory Disease.pptx
How STIs Influence the Development of Pelvic Inflammatory Disease.pptx
FFragrant
 
Flu Vaccine Alert in Bangalore Karnataka
Flu Vaccine Alert in Bangalore KarnatakaFlu Vaccine Alert in Bangalore Karnataka
Flu Vaccine Alert in Bangalore Karnataka
addon Scans
 
NVBDCP.pptx Nation vector borne disease control program
NVBDCP.pptx Nation vector borne disease control programNVBDCP.pptx Nation vector borne disease control program
NVBDCP.pptx Nation vector borne disease control program
Sapna Thakur
 
BENIGN PROSTATIC HYPERPLASIA.BPH. BPHpdf
BENIGN PROSTATIC HYPERPLASIA.BPH. BPHpdfBENIGN PROSTATIC HYPERPLASIA.BPH. BPHpdf
BENIGN PROSTATIC HYPERPLASIA.BPH. BPHpdf
DR SETH JOTHAM
 
Cervical & Brachial Plexus By Dr. RIG.pptx
Cervical & Brachial Plexus By Dr. RIG.pptxCervical & Brachial Plexus By Dr. RIG.pptx
Cervical & Brachial Plexus By Dr. RIG.pptx
Dr. Rabia Inam Gandapore
 
ACUTE SCROTUM.....pdf. ACUTE SCROTAL CONDITIOND
ACUTE SCROTUM.....pdf. ACUTE SCROTAL CONDITIONDACUTE SCROTUM.....pdf. ACUTE SCROTAL CONDITIOND
ACUTE SCROTUM.....pdf. ACUTE SCROTAL CONDITIOND
DR SETH JOTHAM
 
Ophthalmology Clinical Tests for OSCE exam
Ophthalmology Clinical Tests for OSCE examOphthalmology Clinical Tests for OSCE exam
Ophthalmology Clinical Tests for OSCE exam
KafrELShiekh University
 
Hemodialysis: Chapter 3, Dialysis Water Unit - Dr.Gawad
Hemodialysis: Chapter 3, Dialysis Water Unit - Dr.GawadHemodialysis: Chapter 3, Dialysis Water Unit - Dr.Gawad
Hemodialysis: Chapter 3, Dialysis Water Unit - Dr.Gawad
NephroTube - Dr.Gawad
 
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journey
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness JourneyTom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journey
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journey
greendigital
 

Recently uploaded (20)

Novas diretrizes da OMS para os cuidados perinatais de mais qualidade
Novas diretrizes da OMS para os cuidados perinatais de mais qualidadeNovas diretrizes da OMS para os cuidados perinatais de mais qualidade
Novas diretrizes da OMS para os cuidados perinatais de mais qualidade
 
ANATOMY AND PHYSIOLOGY OF URINARY SYSTEM.pptx
ANATOMY AND PHYSIOLOGY OF URINARY SYSTEM.pptxANATOMY AND PHYSIOLOGY OF URINARY SYSTEM.pptx
ANATOMY AND PHYSIOLOGY OF URINARY SYSTEM.pptx
 
Physiology of Chemical Sensation of smell.pdf
Physiology of Chemical Sensation of smell.pdfPhysiology of Chemical Sensation of smell.pdf
Physiology of Chemical Sensation of smell.pdf
 
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?Report Back from SGO 2024: What’s the Latest in Cervical Cancer?
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?
 
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...
 
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...
 
Physiology of Special Chemical Sensation of Taste
Physiology of Special Chemical Sensation of TastePhysiology of Special Chemical Sensation of Taste
Physiology of Special Chemical Sensation of Taste
 
KDIGO 2024 guidelines for diabetologists
KDIGO 2024 guidelines for diabetologistsKDIGO 2024 guidelines for diabetologists
KDIGO 2024 guidelines for diabetologists
 
basicmodesofventilation2022-220313203758.pdf
basicmodesofventilation2022-220313203758.pdfbasicmodesofventilation2022-220313203758.pdf
basicmodesofventilation2022-220313203758.pdf
 
Ocular injury ppt Upendra pal optometrist upums saifai etawah
Ocular injury  ppt  Upendra pal  optometrist upums saifai etawahOcular injury  ppt  Upendra pal  optometrist upums saifai etawah
Ocular injury ppt Upendra pal optometrist upums saifai etawah
 
Knee anatomy and clinical tests 2024.pdf
Knee anatomy and clinical tests 2024.pdfKnee anatomy and clinical tests 2024.pdf
Knee anatomy and clinical tests 2024.pdf
 
How STIs Influence the Development of Pelvic Inflammatory Disease.pptx
How STIs Influence the Development of Pelvic Inflammatory Disease.pptxHow STIs Influence the Development of Pelvic Inflammatory Disease.pptx
How STIs Influence the Development of Pelvic Inflammatory Disease.pptx
 
Flu Vaccine Alert in Bangalore Karnataka
Flu Vaccine Alert in Bangalore KarnatakaFlu Vaccine Alert in Bangalore Karnataka
Flu Vaccine Alert in Bangalore Karnataka
 
NVBDCP.pptx Nation vector borne disease control program
NVBDCP.pptx Nation vector borne disease control programNVBDCP.pptx Nation vector borne disease control program
NVBDCP.pptx Nation vector borne disease control program
 
BENIGN PROSTATIC HYPERPLASIA.BPH. BPHpdf
BENIGN PROSTATIC HYPERPLASIA.BPH. BPHpdfBENIGN PROSTATIC HYPERPLASIA.BPH. BPHpdf
BENIGN PROSTATIC HYPERPLASIA.BPH. BPHpdf
 
Cervical & Brachial Plexus By Dr. RIG.pptx
Cervical & Brachial Plexus By Dr. RIG.pptxCervical & Brachial Plexus By Dr. RIG.pptx
Cervical & Brachial Plexus By Dr. RIG.pptx
 
ACUTE SCROTUM.....pdf. ACUTE SCROTAL CONDITIOND
ACUTE SCROTUM.....pdf. ACUTE SCROTAL CONDITIONDACUTE SCROTUM.....pdf. ACUTE SCROTAL CONDITIOND
ACUTE SCROTUM.....pdf. ACUTE SCROTAL CONDITIOND
 
Ophthalmology Clinical Tests for OSCE exam
Ophthalmology Clinical Tests for OSCE examOphthalmology Clinical Tests for OSCE exam
Ophthalmology Clinical Tests for OSCE exam
 
Hemodialysis: Chapter 3, Dialysis Water Unit - Dr.Gawad
Hemodialysis: Chapter 3, Dialysis Water Unit - Dr.GawadHemodialysis: Chapter 3, Dialysis Water Unit - Dr.Gawad
Hemodialysis: Chapter 3, Dialysis Water Unit - Dr.Gawad
 
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journey
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness JourneyTom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journey
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journey
 

Amer cholesterol metabolism

  • 2. Overview • Introduction • Cholesterol structure • Cholesteryl esters • Cholesterol synthesis • Rate limiting step • Regulation of cholesterol synthesis • Regulation of HMG CoA reductase • Excretion of cholesterol • Hypercholesterolemia and treatment
  • 3. Cholesterol • Most important animal steroid • Maintains membrane fluidity • Insulating effect on nerve fibres • Cholesterol is the parent molecule for – Bile acids and bile salts – Steroid hormones – Vitamin D3
  • 4. Liver plays a central role in the regulation of cholesterol homeostasis
  • 6. Cholesteryl esters • Most plasma cholesterol is esterified with a fatty acid • CEs are not present in membranes • Present in small amounts in most cells • More hydrophobic than cholesterol
  • 7. Cholesterol synthesis • Synthesized in all tissues • Major sites for synthesis: liver, adrenal cortex, testes, ovaries and intestine • All carbon atoms are derived from acetyl CoA • Enzymes involved in biosynthesis are partly located in ER and partly in cytoplasm
  • 8. Synthesis of HMG CoA • HMG CoA is present in both cytosol and mitochondria of liver • Mitochondrial- ketogenesis • Cytosolic – cholesterol synthesis
  • 9. Synthesis of mevalonic acid • Rate limiting and key step • Occurs in cytosol • HMG CoA reductase is an ER membrane enzyme with catalytic unit hanging in the cytosol
  • 10. Further steps in synthesis • Production of a 5-carbon unit: – Isopentinyl pyrophosphate (IPP) • Condensation to a 30C compound: squalene • Cyclization of squalene to 30C lanosterol • Synthesis of 27-Carbon cholesterol (defect in this leads to Smith-Lemli-Opitz Syndrome)
  • 11.
  • 12. Regulation of Cholesterol Synthesis • HMG CoA reductase is the rate-limiting enzyme of cholesterol synthesis
  • 13. HMG CoA Reductase Regulation Gene Transcription Translation HMG CoA Reductase HMG CoA Cholesterol Cholesterol Glucagon Cortisones Statins Insulin Thyroxin
  • 14. HMG CoA Reductase Regulation • Sterol-dependent regulation of gene expression • Sterol-accelerated enzyme degradation • Sterol-independent phosphorylation/dephosphorylation • Hormonal regulation
  • 15. Sterol-dependent regulation of gene expression of HMG CoA • When sufficient cholesterol is present, transcription is suppressed and vice versa • Sterol Regulatory Element (SRE) is a recognition sequence in the DNA • SREBP (SRE binding protein) binding to SRE is essential for transcription of this gene • SREBP cleavage-activating protein (SCAP) is an intracellular cholesterol sensor
  • 16.
  • 17. Sterol-dependent regulation Cholesterol High • SCAP binds to insig protein (insulin-induced protein) in ER membrabe • SCAP-SREBP is retained in the ER • Down regulation of cholesterol synthesis Cholesterol Low • SCAP-SREBP moves to Golgi bodies • SCAP is removed from SREBP • SREBP binds to SRE in DNA • HMG CoA gene is activated
  • 18. Enzyme phosphorylation and dephosphorylation • AMP- activated protein kinase (AMPK) for phosphorylation • Phosphorylated form of enzyme is inactive • Dephosphorylated form is active • Low ATP or High AMP  cholesterol synthesis decreases
  • 19.
  • 20. Hormonal Regulation • Insulin and thyroxine increase upregulation of enzyme expression • Glucagon and cortisol have opposite effect
  • 21. Excretion of cholesterol • By conversion into bile acids and bile salts- excreted in the feces – Secretion of cholesterol in bile – Transported to intestine for elimination • In the intestine, some cholesterol is converted by bacteria into coprostanol and cholestanol before excretion
  • 22. Hypercholesterolemia • High conc. of cholesterol in blood • Leads to atherosclerosis • Statin drugs are used to decrease plasma cholesterol levels • Statins are structural analogs of HMG CoA reductase • Statins inhibit enzyme activity by competitive inhibition
  • 23. β-Sitosterols/ Phytosterols • Plant sterols and are poorly absorbed by humans • Block the absorption of dietary cholesterol • Clinically useful in the dietary treatment of hypercholesterolemia