Lipids - Clinical Applications Flashcards
organic molecules that are soluble in nonpolar solvents but not in polar solvents (e.g., water)
Lipids
After ingested fats (lipids) are cleaved by enzymes they are
absorbed in the small intestine and transported via the lymphatic system into the bloodstream.
circulating lipids are transported in
lipoproteins (insoluble in plasma)
Structural lipids:
Phospholipids, sphingolipids, and glycolipids
Steroids/sterols:
cholesterol, bile acids, and steroid hormones
Lipid classifications
- Simple: Fat/Oil: Fatty acids + Glycerol (Wax: Fatty acids + cetyl alcohol)
- Complex: Phospholipids; Glycolipids; Lipoprotein
- Derived: Derived by hydrolysis: Sterols, fat soluble vitamins and steroid hormones
Function of Lipids
Main function: building blocks of cellular membranes
Other functions:
- Energy storage, mobilization, and utilization
- Prostaglandin, cytokine synthesis
- Cell differentiation and growth
- Signal transmission
- Hormone synthesis
- Bile acid synthesis
Fats are triglycerides that are:
Oils are triglycerides that are:
solids at room temperature.
- usually derived from animals
- mostly saturated fatty acids
Liquids at room temperature
- usually derived from plants or fish
- mostly unsaturated fatty acids
Loose packed fats have _______ melting points
lower
which is why unsaturated fats, such as vegetable oils, are commonly liquid at room temperature
a form of lipid with carbon atoms arranged into four rings
steroids
recommended mg/day of cholesterol as part of the Therapeutic Lifestyle Changes diet
<200 mg/day
the main role of lipoprotein is
to help transport lipids (hydrophobic) in water
Apolipoproteins mainly function as ________ but also serve as _________ for enzymes that metabolize lipoproteins and help in lipid component exchange amoung lipoproteins.
carrier proteins; cofactors
Some examples of lipoproteins include:
- chylomicrons
- very-low-density lipoproteins (VLDL)
- intermediate-density lipoproteins (IDL)
- low-density lipoproteins (LDL)
- high-density lipoproteins (HDL).
large triglyceride-rich particle made in the endoplasmic reticulum of enterocytes of the small intestine.
chylomicrons
They play a role in carrying dietary triglycerides and cholesterol to peripheral tissues and the liver.
an apolipoprotein that is involved in chylomicron assembly, thus having a vital role in the absorption of dietary fats and fat-soluble vitamins.
Apo B-48
triglyceride-rich particles made in the liver.
_______ is important for its production
VLDLs; Apo B-100
are created when triglycerides are removed from VLDL by muscle and adipose tissue.
IDL particles
cholesterol-rich
are formed from VLDL and IDL particles and are also rich in cholesterol.
LDL particles
transports most of the cholesterol in the blood
plays a key role by acting as a ligand for the LDL receptor-mediated uptake of LDL particles by the liver and other tissues
Apo B-100
are cholesterol and phospholipid-rich, and aid in reverse cholesterol transport from peripheral tissues to the liver, where it is removed
HDL particles
Defective lipid metabolism is well known to modulate a wide range of chronic diseases such as:
- cardiovascular diseases
- cancer
- several other genetically defective lipids pathways with severe health implications
Pathophysiological relevance of lipolysis, lipophagy
- Neural Lipid synthesis disease
- Obesity
- Fatty liver disease
- Cholesterol Ester storage disease
- Atherosclerosis
- Lipodystrophies
Abnormal levels of cholesterol and triglycerides in the blood are often due to
the unusual assembly, breakdown, or transport of their lipoprotein particles
are good indicators of the risk of cardiovascular disease (CVD)
levels of plasma lipids
is related to a greater risk of atherosclerotic cardiovascular disease, as well as a higher occurrence of ischemic vascular disease and development of fatty deposits under the skin, known as xanthomas and xanthelasmas.
hyperlipoproteinemia
Cardiovascular disease (CVD) contributes to more than __________ deaths per year globally, which accounts for nearly half of all deaths from non-communicable diseases
17 million
CVD is primarily caused by ___________, a chronic inflammatory disease of the arteries in which the deposition of cholesterol and fibrous materials in artery walls forms a plaque or lesion.
atherosclerosis
Key risk factors that associate with the number of atherosclerotic CVD events include
•include the total concentration of cholesterol found in the blood, as well as the cholesterol found in individual lipoprotein subclasses.
a primary, major risk factor for ASCVD and may even be a prerequisite for ASCVD, occurring before other major risk factors come into play.
Dyslipidemia
Increasing evidence also points to insulin resistance, which results in increased levels of plasma triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) and a decreased concentration of high-density lipoprotein cholesterol (HDL-C) as an important risk factor for
peripheral vascular disease
There are several types and subtypes of lipid-related disorders
Hypertriglyceridemia
hypercholesterolemia
Five main disorders result in hypertriglyceridemia
- Familial hypertriglyceridemia: An autosomal dominant disorder that results in elevated VLDL levels in plasma
- Familial combined hyperlipidemia: An autosomal dominant disorder, characterized by the excessive synthesis of lipoproteins containing apolipoprotein B
- Congenital lipoprotein lipase deficiency: An autosomal recessive disorder, which results in low to no lipoprotein lipase activity; typically, chylomicrons build up in the blood and eruptive xanthomas develop
- Apoprotein CII deficiency: An autosomal recessive disorder, characterized by the lack of apoprotein CII, an essential cofactor for lipoprotein lipase activity; there is usually chylomicron and VLDL accumulation in the plasma
- Familial dysbetalipoproteinemia: A disorder in which there is a defect in apolipoprotein E; due to the buildup of remnant VLDL particles in the blood, there are higher plasma levels of cholesterol and triglyceride
Three main conditions result in hypercholesterolemia
- Polygenic hypercholesterolemia: The most common disorder to raise cholesterol levels; there are many genes involved that elevate LDL concentration in plasma
- Familial hypercholesterolemia: An autosomal dominant disorder in which the gene for the LDL receptor is defective, so removal of LDL from plasma is less than effective.
- Familial hypercholesterolemia is associated with premature ischemic cardiovascular disease;
- Familial combined hyperlipidemia: Discussed previously
High levels of plasma lipids can also be due to dietary factors, such as
- ingesting excess calories
- saturated fatty acids
- cholesterol
- medication use
linked to dysregulation of lipid metabolism, which may result in abnormal levels of blood lipids, ectopic lipid deposition and associated metabolic diseases such as non-alcoholic liver disease (NAFLD) and atherosclerosis.
obesity
Overweight and Obesity
% or young people age 2 to 19 years
% of adults
19%
40%
Two of the leading causes of heart disease and stroke are
high blood pressure and high blood cholesterol
Abnormal lipid levels in childhood and adolescence are linked to
increased risk for CVD in adulthood
Accumulation of LDs in tissues in high amounts may cause chronic inflammation which is identified as one of the hallmarks of
obesity-related metabolic disorders
act like soaps and other emulsifiers: they contain both polar and nonpolar regions, helping to break fats in foods into smaller pieces, allowing them to be hydrolyzed more easily.
bile salts
if cholesterol levels are too high or the levle of bile salts is too low the cholesterol precipitates and forms
gallstones
gallstones can block the duct that allows bile toe become secreted into the duodenum which causes fats to no longer be digested properly, and the bile pigments absorbed into the blood causes:
the skin to become yellow and the stool to become gray
There is no physicological need for:
It is recommended to consume no more than _____% of total calories from it.
saturated fat
10%
Essential fatty acids (FA) and deficiency
Only two FA are essential:
Both are:
Linoleic and alpha-linolenic
Both are (poly)unsaturated
Deficiencies in Linoleic and alpha-linolenic acids can lead to:
- Dermatitis
- Thrombocytopenia
- Increased susceptibility to infections
- Failure to thrive
- History of low fat intake
Elevated plasma triglycerides and very-low-density lipoproteins are directly associated with the risk of
atherosclerotic heart disease, although not as independent as LDL
Disorders associated with malfunctioning of sphingolipid metabolism
- Probably the best known is Tay-Sachs disease, which strikes infants and is typically fatal by age 3.
- Niemann-Pick disease also strikes infants and is fatal early in life.
- Gaucher’s disease and Fabry’s disease strike later in life and are generally less devastating.
Reactive oxygen species (ROS) and ROS-induced oxidative modification of HDL cause
endothelial dysfunction and progression of atherosclerosis
Evidence has accumulated during the past several years that strengthens long-standing AHA recommendations to replace _______with _________ and _________to lower the incidence of CVD
saturated fat; polyunsaturated and monounsaturated fat
Cardiovascular disease (CVD) is the leading global cause of death, accounting for _____deaths per year, comprising _____% of total global deaths in 2013.
Nearly ______people in the United States died of heart disease, stroke, and other CVDs in 2014, translating to about _______deaths.
The annual direct and indirect costs of these deaths total more than _______
17.3 million; 31.5
808 000; 1 of every 3
$316.1Bill
Dietary intake of _____fatty acids is associated with both increased LDL-C and decreased HDL-C levels.
trans
