This document discusses lipid and lipoprotein metabolism. It covers cholesterol and triglyceride synthesis and absorption, the roles of various apolipoproteins and enzymes, reverse cholesterol transport, and how derangements can lead to conditions like metabolic syndrome. Key lipoproteins like LDL, HDL, VLDL, and lipoprotein(a) are examined, as well as their roles in health and disease.
This document discusses lipid and lipoprotein metabolism. Key points include:
1) Cholesterol is synthesized in tissues and absorbed from the diet, while triglycerides are absorbed after dietary fat is broken down.
2) Lipoproteins like LDL and HDL transport lipids in the blood and are composed of a lipid core surrounded by proteins and phospholipids.
3) The liver plays a central role in lipid homeostasis, regulating cholesterol synthesis and bile acid production.
4) Derangements in lipid metabolism can occur in conditions like metabolic syndrome and increase disease risk. Reverse cholesterol transport via HDL is an important protective process.
The bile salts such as cholic acid contain a hydrophobic side and a hydrophilic side, thus allowing bile salts to dissolve at an oil-water interface, with the hydrophobic surface in contact with the non-polar phase and the hydrophilic surface in the aqueous medium. This detergent action emulsifies fats and yields mixed micelles, which allow attack by water-soluble digestive enzymes and facilitate the absorption of lipids through the intestinal mucosa. Mixed Micelles also serve as transport vehicles for those lipids that are less water-soluble than fatty acids, such as cholesterol or the fat-soluble vitamins A, D, E, and K. Thus, efficient absorption of lipids depends on the presence of sufficient bile acids to solubilize the ingested lipids.
This document discusses abetalipoproteinemia, a rare genetic disorder characterized by the lack of apolipoprotein B, which is necessary for the formation of chylomicrons, VLDLs, and LDLs. This leads to an inability to absorb and transport dietary fats and fat-soluble vitamins. Patients with abetalipoproteinemia experience fat accumulation in intestinal and liver cells, malabsorption of fat and fat-soluble vitamins like vitamin E, and associated neurological and vision complications. The underlying genetic defect is mutations in the microsomal triglyceride transfer protein gene, which is essential for producing beta-lipoproteins needed for fat absorption and transport.
Lipoproteins are protein-lipid complexes that transport lipids between tissues. They have an outer surface containing proteins and phospholipids and an inner hydrophobic core containing triglycerides and cholesterol esters. The main classes of lipoproteins are chylomicrons, VLDL, IDL, LDL, and HDL. Chylomicrons transport dietary lipids from the intestine to tissues. VLDL is produced in the liver and transports triglycerides. Through the action of lipoprotein lipase, VLDL loses triglycerides to become IDL and LDL, which transports cholesterol. HDL transports cholesterol from tissues back to the liver in the reverse cholesterol transport pathway. Cholesterol homeostasis is maintained through hepatic
Lipoproteins are complexes of protein and lipids that transport lipids in the bloodstream. There are four main types of lipoproteins: chylomicrons, very low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). Each type has a specific function in lipid transport and metabolism. Chylomicrons transport dietary lipids from the intestine to other tissues, VLDL transports endogenous lipids from the liver, LDL delivers cholesterol to tissues, and HDL transports cholesterol from tissues back to the liver. The apolipoproteins associated with each lipoprotein complex help determine its structure and function in lipid transport and metabolism.
This document discusses lipid metabolism and disorders of lipid metabolism. It covers the biological significance of cholesterol and its conversion into bile acids, steroid hormones, and vitamin D. Key disorders discussed include hypercholesterolemia, atherosclerosis, fatty liver, and obesity. The document provides details on cholesterol metabolism, including biosynthesis of bile acids from cholesterol in the liver, enterohepatic circulation, and the role of bile acids in digestion. It also discusses cholesterol transport via lipoproteins and the roles of HDL and LCAT in cholesterol elimination from the body. Causes and significance of hypercholesterolemia and its association with atherosclerosis and heart disease are summarized.
Cholesterol is converted to bile acids in the liver which aid in digestion. Bile acids are synthesized from cholesterol through a reaction that adds hydroxyl groups. They help emulsify lipids and aid in their absorption. Most bile acids are reabsorbed and recycled in a process called enterohepatic circulation. A small amount of bile acids are lost in feces, which is the main route for eliminating cholesterol from the body. When bile acid or cholesterol levels are too high, gallstones can form. Cholesterol is also a precursor for steroid hormones and vitamin D. High levels of cholesterol in the blood can increase risk of heart disease.
This document discusses hyperlipidemia and various plant constituents that can help treat it. It begins by defining hyperlipidemia and listing some common causes. It then discusses the lipid regulation pathway and how various conditions like diabetes, hypothyroidism, and alcohol use can disrupt this pathway and cause hyperlipidemia. The document focuses on various polyphenolic compounds found in plants that have been shown to help treat hyperlipidemia by modulating the AMPK pathway and SREBP transcription factor to lower cholesterol synthesis and increase excretion. Specific polyphenols discussed include catechins, EGCG, and the Bergamot Polyphenol Fraction.
This document discusses lipid and lipoprotein metabolism. Key points include:
1) Cholesterol is synthesized in tissues and absorbed from the diet, while triglycerides are absorbed after dietary fat is broken down.
2) Lipoproteins like LDL and HDL transport lipids in the blood and are composed of a lipid core surrounded by proteins and phospholipids.
3) The liver plays a central role in lipid homeostasis, regulating cholesterol synthesis and bile acid production.
4) Derangements in lipid metabolism can occur in conditions like metabolic syndrome and increase disease risk. Reverse cholesterol transport via HDL is an important protective process.
The bile salts such as cholic acid contain a hydrophobic side and a hydrophilic side, thus allowing bile salts to dissolve at an oil-water interface, with the hydrophobic surface in contact with the non-polar phase and the hydrophilic surface in the aqueous medium. This detergent action emulsifies fats and yields mixed micelles, which allow attack by water-soluble digestive enzymes and facilitate the absorption of lipids through the intestinal mucosa. Mixed Micelles also serve as transport vehicles for those lipids that are less water-soluble than fatty acids, such as cholesterol or the fat-soluble vitamins A, D, E, and K. Thus, efficient absorption of lipids depends on the presence of sufficient bile acids to solubilize the ingested lipids.
This document discusses abetalipoproteinemia, a rare genetic disorder characterized by the lack of apolipoprotein B, which is necessary for the formation of chylomicrons, VLDLs, and LDLs. This leads to an inability to absorb and transport dietary fats and fat-soluble vitamins. Patients with abetalipoproteinemia experience fat accumulation in intestinal and liver cells, malabsorption of fat and fat-soluble vitamins like vitamin E, and associated neurological and vision complications. The underlying genetic defect is mutations in the microsomal triglyceride transfer protein gene, which is essential for producing beta-lipoproteins needed for fat absorption and transport.
Lipoproteins are protein-lipid complexes that transport lipids between tissues. They have an outer surface containing proteins and phospholipids and an inner hydrophobic core containing triglycerides and cholesterol esters. The main classes of lipoproteins are chylomicrons, VLDL, IDL, LDL, and HDL. Chylomicrons transport dietary lipids from the intestine to tissues. VLDL is produced in the liver and transports triglycerides. Through the action of lipoprotein lipase, VLDL loses triglycerides to become IDL and LDL, which transports cholesterol. HDL transports cholesterol from tissues back to the liver in the reverse cholesterol transport pathway. Cholesterol homeostasis is maintained through hepatic
Lipoproteins are complexes of protein and lipids that transport lipids in the bloodstream. There are four main types of lipoproteins: chylomicrons, very low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). Each type has a specific function in lipid transport and metabolism. Chylomicrons transport dietary lipids from the intestine to other tissues, VLDL transports endogenous lipids from the liver, LDL delivers cholesterol to tissues, and HDL transports cholesterol from tissues back to the liver. The apolipoproteins associated with each lipoprotein complex help determine its structure and function in lipid transport and metabolism.
This document discusses lipid metabolism and disorders of lipid metabolism. It covers the biological significance of cholesterol and its conversion into bile acids, steroid hormones, and vitamin D. Key disorders discussed include hypercholesterolemia, atherosclerosis, fatty liver, and obesity. The document provides details on cholesterol metabolism, including biosynthesis of bile acids from cholesterol in the liver, enterohepatic circulation, and the role of bile acids in digestion. It also discusses cholesterol transport via lipoproteins and the roles of HDL and LCAT in cholesterol elimination from the body. Causes and significance of hypercholesterolemia and its association with atherosclerosis and heart disease are summarized.
Cholesterol is converted to bile acids in the liver which aid in digestion. Bile acids are synthesized from cholesterol through a reaction that adds hydroxyl groups. They help emulsify lipids and aid in their absorption. Most bile acids are reabsorbed and recycled in a process called enterohepatic circulation. A small amount of bile acids are lost in feces, which is the main route for eliminating cholesterol from the body. When bile acid or cholesterol levels are too high, gallstones can form. Cholesterol is also a precursor for steroid hormones and vitamin D. High levels of cholesterol in the blood can increase risk of heart disease.
This document discusses hyperlipidemia and various plant constituents that can help treat it. It begins by defining hyperlipidemia and listing some common causes. It then discusses the lipid regulation pathway and how various conditions like diabetes, hypothyroidism, and alcohol use can disrupt this pathway and cause hyperlipidemia. The document focuses on various polyphenolic compounds found in plants that have been shown to help treat hyperlipidemia by modulating the AMPK pathway and SREBP transcription factor to lower cholesterol synthesis and increase excretion. Specific polyphenols discussed include catechins, EGCG, and the Bergamot Polyphenol Fraction.
1. Lipids serve important roles in organisms as metabolic fuels, components of cell membranes, and insulators. Cholesterol is present in plasma as esters and acts as a precursor for steroid hormones and bile acids. Triacylglycerols and phospholipids are important energy sources and structural components of cell membranes.
2. Fatty acids exist as essential and non-essential forms, occurring in plasma as esters or in free form. They are stored as triacylglycerols in fat tissue and released during lipolysis to act as an energy source for liver, heart and muscles.
3. Disorders of lipid metabolism include both primary causes like genetic familial hypercholesterolemia and secondary causes
This document provides an outline for a lecture on lipids and lipoproteins. It begins by defining key terms related to lipids and lipoproteins and describing the different classes of lipids and lipoproteins, including chylomicrons, VLDL, LDL, and HDL. It then discusses apolipoproteins and their functions. The document outlines the laboratory procedures for determining lipid and lipoprotein levels and interpreting the results. It also discusses the significance of lipids and lipoproteins in conditions like atherosclerosis.
Lipoprotein introduction, their general characteristics, exogenous and endogenous metabolism focusing on chylomicron and vldl metabolism, ldl metabolism and HDL metabolism , reverse cholesterol transport.
This document provides information about lipid digestion and absorption. It discusses:
1) The digestion of lipids by pancreatic lipases and other enzymes in the small intestine.
2) The absorption of lipids into mucosal cells through micelle formation.
3) The transport of lipids from enterocytes to the lymphatic system and blood in the form of chylomicrons.
4) The roles of lipoproteins like VLDL, LDL, and HDL in transporting lipids between tissues.
Cholesterol is one of the most studied molecules in biology. It plays essential roles in animal cell membranes and is a precursor for bile acids, steroid hormones, and vitamin D. Cholesterol is synthesized endogenously through a complex multi-step process and is also obtained through diet. High levels of cholesterol are linked to atherosclerosis and heart disease, while adequate levels are important for various biological functions. Tight regulation of cholesterol homeostasis is necessary for health.
Cholesterol is synthesized in the body and obtained through diet. It has important functions but excess can promote atherosclerosis. Cholesterol synthesis occurs mainly in the liver and involves four stages. The rate-limiting enzyme HMG-CoA reductase is regulated by phosphorylation/dephosphorylation and repression/derepression. Cholesterol levels in cells are regulated by LDL receptor uptake and catabolism to bile acids. High LDL and triglycerides increase atherosclerosis risk while high HDL is protective. Risk factors like these are addressed through dietary and drug measures like statins that lower cholesterol synthesis.
What are lipoproteins?
Structure of lipoprotein complex.
Classification of lipoproteins.
Important enzyme and protein involved in lipoprotein metabolism.
Apolipoprotein.
Lipoprotein metabolism.
Clinical disorders
Importance of lipoprotein.
Conclusion
Reference.
Coronary heart disease due to atherosclerotic process is the major cause of death.Lipids have been implicated for enhanced atherosclerosis. The major lipids involved are triacy glycerol and cholesterol which are transported in the plasma by lipoproteins. So a better understanding of lipid transport and its abnormalities is essential for medical and health professional students.
1) Chylomicrons are assembled in the intestines and carry dietary lipids through the lymphatic system and bloodstream to tissues. They are formed when apo B-48 is loaded with lipids by MTP in the ER and Golgi.
2) Nascent chylomicrons acquire apo C and E from HDL in the bloodstream. Lipoprotein lipase on capillary walls hydrolyzes chylomicron triglycerides, providing fatty acids to tissues.
3) Remnant chylomicrons are taken up by the liver via apo E binding to hepatic receptors, where lipids are metabolized and reused or stored.
This document discusses lipoprotein metabolism. Lipoproteins are particles that carry lipids like triglycerides and cholesterol through the water-based bloodstream. They are composed of a hydrophobic core of lipids surrounded by a surface layer of phospholipids and apolipoproteins. The main lipoproteins are chylomicrons, VLDL, IDL, LDL, and HDL. The document details how these lipoproteins are formed, the lipids they carry, their roles in lipid transport, and regulation of their metabolism by factors like diet, exercise, and enzymes. Maintaining healthy lipoprotein levels is important for cardiovascular health.
The document discusses lipid transport and the major classes of lipoproteins in the bloodstream:
1. Chylomicrons transport dietary lipids from the intestine.
2. Very low-density lipoproteins (VLDL) transport lipids from the liver.
3. Low-density lipoproteins (LDL) are formed from VLDL and transport cholesterol to tissues.
4. High-density lipoproteins (HDL) transport cholesterol from tissues back to the liver.
The document outlines lipoprotein structure and function, including:
- Lipoproteins are protein-lipid complexes that transport lipids between tissues. They have a hydrophobic core of triglycerides and cholesterol esters surrounded by a hydrophilic surface.
- The main classes of lipoproteins are chylomicrons, VLDL, IDL, LDL, and HDL. They differ in size, density, and protein/lipid content.
- Apolipoproteins associated with each lipoprotein help with structure and regulate metabolism. Chylomicrons contain apoB-48 and transport dietary lipids. VLDL contains apoB-100 and transports endogenous lipids.
This document summarizes various aspects of lipoproteins, lipids, and treatments for hyperlipidemia. It discusses the main classes of lipoproteins such as chylomicrons, VLDL, LDL, HDL and their roles in transporting lipids like cholesterol and triglycerides. It also outlines drug classes used to treat hyperlipidemia, including fibrates, statins, bile acid sequestrants, and niacin. Adverse effects and guidelines for drug combinations are provided.
This document summarizes various types of lipids and lipoproteins, including their functions, components, and roles in atherosclerosis and coronary heart disease. It also discusses factors that influence lipid levels and guidelines for treatment and management of dyslipidemia through lifestyle modifications and lipid-altering drugs such as statins, fibrates, bile acid sequestrants, and niacin.
lipoproteins types and classication in the body and role of them in diagnosis...ROOPAR45
The document discusses different classes of lipoproteins, including chylomicrons, very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), low density lipoproteins (LDL), and high density lipoproteins (HDL). It describes the separation techniques, composition, sites of synthesis, functions, and disorders associated with each class. Characteristics such as density, diameter, electrophoretic mobility, major lipids, and apolipoproteins are compared among the different classes.
Lipoproteins are complexes of lipids and proteins that transport lipids through the bloodstream. There are four main types of plasma lipoproteins - chylomicrons, VLDL, LDL, and HDL - which differ in size, density, and lipid/protein composition. Chylomicrons carry dietary lipids from the intestine to other tissues, VLDL transports endogenous lipids from the liver, LDL carries cholesterol, and HDL transports cholesterol from tissues to the liver for processing or excretion. The metabolism and interactions between these lipoproteins, such as the transfer of lipids between them, are tightly regulated and essential for maintaining lipid homeostasis.
1. Lipids serve important roles in organisms as metabolic fuels, components of cell membranes, and insulators. Cholesterol is present in plasma as esters and acts as a precursor for steroid hormones and bile acids. Triacylglycerols and phospholipids are important energy sources and structural components of cell membranes.
2. Fatty acids exist as essential and non-essential forms, occurring in plasma as esters or in free form. They are stored as triacylglycerols in fat tissue and released during lipolysis to act as an energy source for liver, heart and muscles.
3. Disorders of lipid metabolism include both primary causes like genetic familial hypercholesterolemia and secondary causes
This document provides an outline for a lecture on lipids and lipoproteins. It begins by defining key terms related to lipids and lipoproteins and describing the different classes of lipids and lipoproteins, including chylomicrons, VLDL, LDL, and HDL. It then discusses apolipoproteins and their functions. The document outlines the laboratory procedures for determining lipid and lipoprotein levels and interpreting the results. It also discusses the significance of lipids and lipoproteins in conditions like atherosclerosis.
Lipoprotein introduction, their general characteristics, exogenous and endogenous metabolism focusing on chylomicron and vldl metabolism, ldl metabolism and HDL metabolism , reverse cholesterol transport.
This document provides information about lipid digestion and absorption. It discusses:
1) The digestion of lipids by pancreatic lipases and other enzymes in the small intestine.
2) The absorption of lipids into mucosal cells through micelle formation.
3) The transport of lipids from enterocytes to the lymphatic system and blood in the form of chylomicrons.
4) The roles of lipoproteins like VLDL, LDL, and HDL in transporting lipids between tissues.
Cholesterol is one of the most studied molecules in biology. It plays essential roles in animal cell membranes and is a precursor for bile acids, steroid hormones, and vitamin D. Cholesterol is synthesized endogenously through a complex multi-step process and is also obtained through diet. High levels of cholesterol are linked to atherosclerosis and heart disease, while adequate levels are important for various biological functions. Tight regulation of cholesterol homeostasis is necessary for health.
Cholesterol is synthesized in the body and obtained through diet. It has important functions but excess can promote atherosclerosis. Cholesterol synthesis occurs mainly in the liver and involves four stages. The rate-limiting enzyme HMG-CoA reductase is regulated by phosphorylation/dephosphorylation and repression/derepression. Cholesterol levels in cells are regulated by LDL receptor uptake and catabolism to bile acids. High LDL and triglycerides increase atherosclerosis risk while high HDL is protective. Risk factors like these are addressed through dietary and drug measures like statins that lower cholesterol synthesis.
What are lipoproteins?
Structure of lipoprotein complex.
Classification of lipoproteins.
Important enzyme and protein involved in lipoprotein metabolism.
Apolipoprotein.
Lipoprotein metabolism.
Clinical disorders
Importance of lipoprotein.
Conclusion
Reference.
Coronary heart disease due to atherosclerotic process is the major cause of death.Lipids have been implicated for enhanced atherosclerosis. The major lipids involved are triacy glycerol and cholesterol which are transported in the plasma by lipoproteins. So a better understanding of lipid transport and its abnormalities is essential for medical and health professional students.
1) Chylomicrons are assembled in the intestines and carry dietary lipids through the lymphatic system and bloodstream to tissues. They are formed when apo B-48 is loaded with lipids by MTP in the ER and Golgi.
2) Nascent chylomicrons acquire apo C and E from HDL in the bloodstream. Lipoprotein lipase on capillary walls hydrolyzes chylomicron triglycerides, providing fatty acids to tissues.
3) Remnant chylomicrons are taken up by the liver via apo E binding to hepatic receptors, where lipids are metabolized and reused or stored.
This document discusses lipoprotein metabolism. Lipoproteins are particles that carry lipids like triglycerides and cholesterol through the water-based bloodstream. They are composed of a hydrophobic core of lipids surrounded by a surface layer of phospholipids and apolipoproteins. The main lipoproteins are chylomicrons, VLDL, IDL, LDL, and HDL. The document details how these lipoproteins are formed, the lipids they carry, their roles in lipid transport, and regulation of their metabolism by factors like diet, exercise, and enzymes. Maintaining healthy lipoprotein levels is important for cardiovascular health.
The document discusses lipid transport and the major classes of lipoproteins in the bloodstream:
1. Chylomicrons transport dietary lipids from the intestine.
2. Very low-density lipoproteins (VLDL) transport lipids from the liver.
3. Low-density lipoproteins (LDL) are formed from VLDL and transport cholesterol to tissues.
4. High-density lipoproteins (HDL) transport cholesterol from tissues back to the liver.
The document outlines lipoprotein structure and function, including:
- Lipoproteins are protein-lipid complexes that transport lipids between tissues. They have a hydrophobic core of triglycerides and cholesterol esters surrounded by a hydrophilic surface.
- The main classes of lipoproteins are chylomicrons, VLDL, IDL, LDL, and HDL. They differ in size, density, and protein/lipid content.
- Apolipoproteins associated with each lipoprotein help with structure and regulate metabolism. Chylomicrons contain apoB-48 and transport dietary lipids. VLDL contains apoB-100 and transports endogenous lipids.
This document summarizes various aspects of lipoproteins, lipids, and treatments for hyperlipidemia. It discusses the main classes of lipoproteins such as chylomicrons, VLDL, LDL, HDL and their roles in transporting lipids like cholesterol and triglycerides. It also outlines drug classes used to treat hyperlipidemia, including fibrates, statins, bile acid sequestrants, and niacin. Adverse effects and guidelines for drug combinations are provided.
This document summarizes various types of lipids and lipoproteins, including their functions, components, and roles in atherosclerosis and coronary heart disease. It also discusses factors that influence lipid levels and guidelines for treatment and management of dyslipidemia through lifestyle modifications and lipid-altering drugs such as statins, fibrates, bile acid sequestrants, and niacin.
lipoproteins types and classication in the body and role of them in diagnosis...ROOPAR45
The document discusses different classes of lipoproteins, including chylomicrons, very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), low density lipoproteins (LDL), and high density lipoproteins (HDL). It describes the separation techniques, composition, sites of synthesis, functions, and disorders associated with each class. Characteristics such as density, diameter, electrophoretic mobility, major lipids, and apolipoproteins are compared among the different classes.
Lipoproteins are complexes of lipids and proteins that transport lipids through the bloodstream. There are four main types of plasma lipoproteins - chylomicrons, VLDL, LDL, and HDL - which differ in size, density, and lipid/protein composition. Chylomicrons carry dietary lipids from the intestine to other tissues, VLDL transports endogenous lipids from the liver, LDL carries cholesterol, and HDL transports cholesterol from tissues to the liver for processing or excretion. The metabolism and interactions between these lipoproteins, such as the transfer of lipids between them, are tightly regulated and essential for maintaining lipid homeostasis.
Joyce M Sullivan, Founder & CEO of SocMediaFin, Inc. shares her "Five Questions - The Story of You", "Reflections - What Matters to You?" and "The Three Circle Exercise" to guide those evaluating what their next move may be in their careers.
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Eirini is an HR professional with strong passion for technology and semiconductors industry in particular. She started her career as a software recruiter in 2012, and developed an interest for business development, talent enablement and innovation which later got her setting up the concept of Software Community Management in ASML, and to Developer Relations today. She holds a bachelor degree in Lifelong Learning and an MBA specialised in Strategic Human Resources Management. She is a world citizen, having grown up in Greece, she studied and kickstarted her career in The Netherlands and can currently be found in Santa Clara, CA.
Success is often not achievable without facing and overcoming obstacles along the way. To reach our goals and achieve success, it is important to understand and resolve the obstacles that come in our way.
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A Guide to a Winning Interview June 2024Bruce Bennett
This webinar is an in-depth review of the interview process. Preparation is a key element to acing an interview. Learn the best approaches from the initial phone screen to the face-to-face meeting with the hiring manager. You will hear great answers to several standard questions, including the dreaded “Tell Me About Yourself”.
3. HMG CoA Reductase
(More Than Cholesterol Synthesis)
Acetyl CoA
HMG CoA
Mevalonate
Farnesyl Pyrophosphate
Cholesterol
HMG CoA Reductase
Isopentenyl
adenine
(transfer RNA)
Prenylation of
signalling peptides
(ras, rho, etc.)
Ubiquinones
(CoQ-10, etc.)
Dolichols
Inhibition of other key products of mevalonate may relate to
nonlipid effects & rare side effects of statins.
6. Key concepts: synthesis
– Primary synthetic sites are extrahepatic, but liver
is key regulator of homeostasis
Key concepts: absorption
– Largest source is biliary secretion, not diet.
– Normal absorption: 50%
– For cholesterol to be absorbed it must:
• undergo hydrolysis (de-esterification by esterases)
• be incorporated into micelles
• be taken up by cholesterol transporter
• be re-esterified and incorporated into chylomicrons
NORMAL CHOLESTEROL METABOLISM
9. STRUCTURE OF PLANT STEROL ESTERS
HO
Cholesterol
Sitosterol
HO
O
C - O
Sitosterol Ester
10. 400 mg/day
1,300 mg/day
17,400 mg/day
850 mg/day
NORMAL CHOLESTEROL ABSORPTION
Ezetimibe competes
For cholesterol here
Oil phase
11. 400 mg/day
1,300 mg/day
17,400 mg/day
850 mg/day
NORMAL CHOLESTEROL ABSORPTION
Defect in ABCG5/G8
transporter causes
phytosterolemia
Oil phase
12. Role of Bile Salts, cholesterol, phospholipids in
gall stone formation.
Importance of Bile Salts for cholesterol absorption
NORMAL CHOLESTEROL METABOLISM
Key concepts: bile salt absorption inhibitors
– Bile acid binding compounds:
• Welchol
• Cholestyramine
• Colestipol
• Fiber
– Surgery: Partial ileal bypass.
15. 17 G
BA*
NORMAL CHOLESTEROL METABOLISM
Tissue
pools
70G
0.8 G
SYN CHOL
17.35 G
BA*
0.85 G
ABS CHOL
0.35 G BA*
.35 G
.65 G
.20 G
1.20 G
CHOL + BA
50% 95%
0.4 G CHOL
1.3 G
CHOL
* BA = BILE ACIDS
.20 G CHOL 0.65 G CHOL
16. Key concepts: absorption
– Triglyceride (i.e. energy) assimilation is key to
the survival of the organism.
– Dietary triglyceride must be hydrolyzed to fatty
acids, mono-glycerides and glycerol prior to
absorption.
– Fatty acids must partition to micellar phase for
absorption.
– For transport, triglyceride must be reconstituted
from glycerol and fatty acid and incorporated into
chylomicrons.
NORMAL TRIGLYCERIDE METABOLISM
17. Structures of Fatty Acids
C
HO
O
C
HO
O
C
HO
O
C
HO
O
C
HO
O
18:0
cis-18:1 -6
trans-18:1 -6
18:2 -6
18:3 -3
18. Structures of Fatty Acids
C
HO
O
C
HO
O
C
HO
O
C
HO
O
C
HO
O
16:0 (palmitic)
cis-18:1 -6 (oleic)
trans-18:1 -6 (elaidic
18:2 -6 (linoleic)
18:3 -3
(alpha
linolenic)
C
HO
O 20:5 -3 (EPA)
22. Effect of Carbohydrate Restriction on
Carbohydrate-induced Hypertriglyceridemia
0
500
1000
1500
2000
2500
3000
Initial Level End of Fast Inpatient Low
CHO Diet
Outpatient
Low CHO Diet
Reisell et al., Am J Clin Nutr 1966;19:84
Treatment: Fast for average 5 days, then consume low CHO diet.
Composition
of diet:
7-15% CHO
25-30% Prot
60-65% Fat
32. Pancreatic Lipase Movement
Most pancreatic
lipase is secreted
into the pancreatic
duct, but some moves
back into capillaries.
33. Chylomicron Role in Pancreatitis
Pancreatic lipase acts
on chylomicrons
adherent to capillary
endothelium, producing
fatty acid anions, or
soaps. By detergent
action, cell membranes
are disrupted, releasing
more lipase, and
additional fatty acid
anions are produced in
a vicious cycle.
44. Distribution of LDL Size Phenotypes
According to Triglyceride Levels
0
10
20
30
40
50
60
70
80
90
100
0 50 100 150 200 250 300
Phenotype A
(light fluffy LDL)
Phenotype B
(small dense LDL)
Cumulative
percent
of
cases
Triglyceride (mg/dl)
Austin et al, Circulation 1990; 82:495
45. Peroxisome Proliferator-Activated Receptor:
A Nuclear Receptor for Metabolic Genes
a, Basic mechanism of action of
nuclear hormone receptors: bind
to a specific sequence in the
promoter of target genes (called
hormone response elements), and
activate transcription upon
binding of ligand. Several nuclear
hormone receptors, including
the retinoic acid receptor, the
vitamin D receptor and PPAR, can
bind to DNA only as a heterodimer
with the retinoid X receptor, RXR,
as shown. b, some PPAR and
PPAR ligands.
Kersten et al. Roles of PPARs in health
and disease. Nature 2000; 405: 421-424
46. Role of PPAR* and in VLDL,
LDL
and HDL metabolism
* Peroxisome Proliferator Activated Receptor
PPAR
Tissues: Liver, kidney, heart,
muscle.
Ligands: fatty acids, fibrates
Actions: Stimulate production
of apo A I, lipoprotein lipase,
increase expression of ABC
A-1, increase FFA uptake and
catabolism, decrease FFA
and VLDL synthesis.
PPAR
Tissues: Adipose tissue and
intestine.
Ligands: arachidonic acid,
Glitazones
Actions: increase expression of
ABC A-1, increase FFA synthesis
and uptake by adipocytes, increase
insulin sensitivity (?)
53. LDL-R
50% of HDL C may
Return to the liver
On LDL via CETP
HDL and Reverse Cholesterol Transport
54. • An atherogenic lipoprotein
containing apo(a) and apoB.
• 20-30% of people have levels
suggesting C-V risk.
• Black subjects have Lp(a)
normal range twice as high
as white and Asiatic subjects.
• Apo(a) sequence similar to plasminogen, and Lp(a)
interferes with spontaneous thrombolysis.
• Lp(a) levels highly genetic, resistant to diet and drug
therapy, although niacin may help.
“LDL”
Apo(a)
-S-S-
Lipoprotein(a), or Lp(a)
55.
56.
57. Summary – Lipid and
Lipoprotein Metabolism
• Cholesterol absorption, synthesis, and
disposition
• Triglyceride/fatty acid transformations and
energy metabolism
• Lipoprotein core and surface components
• Lipoprotein origins and destinations governed
by apo’s
• Derangement in the metabolic syndrome
• Reverse cholesterol transport – the dominant
direction
• Lipoprotein(a)
• Lipoproteins in the arterial wall