Partial 4 - Lipoproteins Flashcards
Lipoproteins consist of
nonpolar lipid core of TAGs, cholesteryl esters, then monolayer of amphipathic lipids such as phospholipids and two types of proteins
Apo A-I
is the principal protein in HDL and activates LCAT
Apo A-II
occurs as dimer mainly in HDL and enhances hepatic lipase activity
Apo B-48
is found only in chylomicrons, enhances chylomicron secretion from intestine, lacks the LDL receptor binding domain in Apo B-100
Apo B-100
is the principal protein in LDL that binds to LDL receptor
Apo C-I
is found in Chylomicrons, VLDL, and HDL and may also activate LCAT
Apo C-II
is found in chylomicrons, VLDL, and HDL and activates lipoprotein lipase
Apo C-III
is found in chylomicron, VLDL, IDL, and HDL and inhibits lipoprotein lipase by inhibiting Apo C-II
Apo D
is found in HDL and is also called cholesterol ester transfer protein (CETP)
Apo E
is found in chylomicron, VLDL, IDL, and HDL and binds to LDL receptor and chylomicron remnant receptor in liver
Apo H
is found in chylomicrons and is also known as β-2-glycoprotein I and is involved in TAG metabolism
Apo E4
is implicated in Alzheimer`s disease and other neurological conditions.
Atherosclerosis, impaired congnitive function, reduced hippocampal volume, HIV, ischemic cerebrovascular disease, faster progression in Multiple Sclerosis, Sleep apnea
All apoproteins are found in chylomicrons except
B-100 and D
Which LDL values are desirable, borderline high and high
Desirable: <130 mg/dl
Borderline high 130-159 mg/dl
High: >160 mg/dl
HDL are composed of
They are mainly composed of proteins (50%) and cholesteryl esters (20%).
HDL is formed
in liver and intestine where it interacts with chylomicron remnants and LCAT to form HDL3 by taking up cholesterol from peripheral tissues via a lipid transporter called ABCA1 (ATP-binding cassette transporter)
Lipoproteins (a) - Lp (a)
They are altered form of LDL that contains apoB-100 covalently linked to apo A, and is considered to be an independent risk factor for the development of atherosclerosis.
Lp (a) mechanism
enhances cholesterol delivery to injured blood vessels, suppresses the generation of plasmin, and promotes smooth muscle proliferation
The primary and secondary bile acids are reabsorbed from
Almost exclusively in the ileum returning to the liver by way of the portal circulation (enterohepatic circulation)
HLP Type I
Familial lipoprotein lipase deficiency (Type I hyperlipoproteinemia) is a rare disorder caused by deficiency of lipoprotein lipase or its coenzyme, apolipoprotein C-II. There is also reduced HDL. The result is fasting chylomicronemia and hypertriacylglycerolemia.
HLP Type II-A
A deficiency of functional LDL receptors (thus LDL catabolism) causes a significant elevation in plasma LDL and, therefore, of plasma cholesterol. Patients with such deficiencies have Type II hyperlipidemia (familial hypercholesterolemia, FH) and premature atherosclerosis, with xanthomas of skin and tendons
HLP Type II-B
Defect in HMG-CoA reductase. Increased production of VLDL and impaired LDL catabolism leads to raised VLDL and LDL. There is also often reduced HDL.
HLP Type III
Defective recognition of apo E2 which causes deficiency in clearance of IDL. These individuals have familial Type III hyperlipoproteinemia (dysbetalipoproteinemia), with hypercholesterolemia, Triglycerides and premature atherosclerosis (formerly known as broad beta disease).
HLP Type IV
(Familial combined hyperlipidemia) Hyperprebetalipoproteinemia is due to impaired VLDL catabolism and thus associated with raised levels of VLDL (and thus TAG levels) and often reduced HDL.
HLP Type V
Hyperlipoproteinemia type V, also known as mixed hyperlipoprotenemia is very similar to type I, but with high VLDL in addition to chylomicrons. It happens due to decreased lipoprotein lipase (Apo C-II deficiency), in addition to VLDL hypersecretion. This leads to raised levels of chylomicrons and VLDL.
In atherogenesis endothelial dysfunction leads to
decreased synthesis of vasodilators and increased synthesis of vasoconstrictors, as well as it leads to increased flux of LDL into arterial wall
Macrophages recognize oxidized lipoproteins through
Scavanger receptors, where they engulf them and become foam cells
What other cells then macrophages can become foam cells?
Smooth muscle cells
Two most common causes of endothelial dysfunction
Hemodynamic disturbances and hypercholesterolemia
Hemodynamic disturbances means
where the is turbulent blood flow (ostia of vessels, at branch points, along posterior wall of the abdominal aorta etc.)
Mediators commonly seen in atherosclerotic lesions
Monocyte chemoattractant protein 1 (MCP-1)
Tumor necrosis factor alpha (TNFa)
Intracellular adhesion molecule 1 (ICAM-1)
Vascular cell adhesion molecule (VCAM-1)
Lipid profile
Total cholesterol level should be lower than 200 mg/dl
LDL-cholesterol should be lower than 100 mg/dl
HDL-cholesterol should be higher than 60 mg/dl
TAGs should be lower than 150 mg/dl.
Metabolic syndrome is characterized by
central obesity (more than 40 inches in men and 35 in women), insulin resistance (fasting glucose 110-125 mg/dL), hypertension (blood pressure 130/85), dyslipidemia HDL cholesterol in men less than 40 mg/dL and less than 50 mg/dL in women, and TAGs more than 150 mg/dL), hypercoagulability, and a proinflammatory state.
Primary dyslipidemias include
Chylomicronemia, hypercholesterolemia, dysbetalipoproteinemia, hypertriglyceridemia, mixed hyperlipoproteinemia, and combined
Secondary dyslipidemias is caused by other diseases such as
Diabetes mellitus, pancreatitis, renal disease, hypothyroidism
Primary (genetic) causes of low HDL
(1) Tangier disease
(2) Familial hypo-α-lipoproteinemia
(3) Apo A-I deficiency
(4) LCAT deficiency
(5) CETP deficiency leading to increased apo A-I, HDL- C enriched in CE
(6) Hepatic lipase deficiency
Tangier disease
defects in ABCA1 transporter which promotes movement of cholesterol from peripheral cells to the lipid-poor HDL cholesterol, and is characterized by accelerated atherosclerosis and little or no HDL cholesterol, as well as accelerated catabolism of apo A-I + II, and cholesterol accumulation leads to enlarge orange tonsils, hepatosplenomegaly, and peripheral neuropathy
Two forms of LCAT deficiency
Familial LCAT deficiency (complete) or partial LCAT deficiency (Fish-eye disease)
Chylomicron function
carry dietary TAGs, cholesterol, Fat-soluble vitamins, and cholesteryl esters to the peripheral tissues
Where is lipoprotein lipase most abundant?
Cardiac muscle
Abetalipoproteinemia
Abetalipoproteinemia is a rare hypolipoproteinemia caused by a defect in microsomal triacylglycerol transfer protein (MTP), leading to an inability to load apo B with lipid. As a consequence, no VLDL or chylomicrons are formed, and triacylglycerols accumulate in the liver and intestine.
What levels of triglyceride levels are classified as abnormal
> 200 mg/dL are classified as abnormal
150-200 mg/dL is borderline high
<150 mg/dL is normal
