Lipids and lipid disorders

Lipids

• Composed mostly of carbon-hydrogen (C-H) bonds
• Serve as energy storage for excess calories
• Function as precursors for various biomolecules:
  • Steroid hormones
  • Prostaglandins
  • Leukotrienes
  • Lipoxins

Fatty Acids

• Chains of carbon-hydrogen bonds terminating with a carboxyl (-COOH) group
• In plasma, mostly non-covalently bound to albumin

Classification of Fatty Acids by Length

• Fatty acids with 4 to 6 carbon atoms are classified as short-chain fatty acids
• Medium-chain fatty acids have 8 to 12 carbon atoms
• Long-chain fatty acids have more than 12 carbon atoms

Classification of Fatty Acids by Bonding

• Unesterified fatty acids are bound to albumin
• Esterified fatty acids are constituents of triglycerides or phospholipids

Classification of Fatty Acids

• Classified according to the number of C=C double bonds present
• Three categories: Saturated, Monounsaturated, and Polyunsaturated

Saturated Fatty Acids

• Have no double bonds

Monounsaturated Fatty Acids

• Contain one double bond

Polyunsaturated Fatty Acids

• Contain 2 or more double bonds

Triglycerides

• Composed of 3 fatty acids attached to 1 molecule of glycerol
• Held together by ester bonds
• No charged groups, making them water insoluble
• Classified as neutral lipids

Phospholipids

• Consist of 2 fatty acids attached to 1 molecule of glycerol
• 3rd position contains phospholipid head groups
• Amphipathic, meaning they have:
  • Hydrophobic (water-repelling) tails
  • Hydrophilic (water-attracting) heads

Cholesterol

• Unsaturated steroid alcohol
• Composed of 4 rings
• Has a single C-H side chain tail
• Also an amphipathic lipid

Classification of Cholesterol

• Cholesterol exists in two forms: unesterified (free cholesterol) and esterified (cholesteryl ester)
• Cholesteryl ester is a neutral lipid

Lipoprotein Characteristics

• Lipoproteins are typically spherical in shape
• Lipoproteins range in size from 10-1200 nm
• Lipoproteins are composed of two main components: lipids and proteins

Lipoproteins: Chylomicrons

• Chylomicrons are the largest lipoproteins and have the lowest density.
• They are formed in the intestines and transport triglycerides after a meal, giving serum a turbid appearance.
• Due to their low density, chylomicrons will float to the top and form a creamy layer when plasma is stored overnight.
• Composition of chylomicrons:
  • 86% triglyceride
  • 5% cholesterol
  • 7% phospholipid
  • 2% apolipoprotein
• Apoproteins present on the surface of chylomicrons:
  • Mainly apoprotein B-48
  • Lesser amounts of apoproteins A-I, C-I, C-II, and C-III

VLDL Composition and Function

• VLDL (Very Low-Density Lipoprotein) carries endogenous triglycerides synthesized in the liver.
• VLDL molecules consist of:
  • 55% triglycerides
  • 19% cholesterol
  • 18% phospholipid
  • 8% apolipoprotein
• VLDLs have the following apolipoproteins on their surface:
  • Apolipoprotein B-100 (mainly)
  • Apolipoprotein C-I
  • Apolipoprotein C-II
  • Apolipoprotein C-III
  • Apolipoprotein E
• Normal lipid metabolism: VLDLs are secreted into the blood by the liver for metabolism in peripheral tissues.

IDL (Intermediate-Density Lipoprotein)

• A transitional form of lipoprotein formed from VLDL (Very-Low-Density Lipoprotein)
• Modified in the liver to form LDL (Low-Density Lipoprotein)
• Carries endogenous triglycerides and cholesterol esters
• Composed of:
  • 23% triglycerides
  • 38% cholesterol
  • 19% phospholipid
  • 19% apolipoprotein
• Surface apolipoproteins include:
  • Mainly B-100
  • Some E

Low-Density Lipoprotein (LDL)

• LDL is the body's major cholesterol carrier, transporting a large amount of endogenous cholesterol.
• LDL is commonly known as "bad cholesterol" due to its association with increased risk for atherosclerosis when levels are elevated.
• LDLs are composed of:
  • 50% cholesterol
  • 22% phospholipids
  • 6% triglycerides
  • 22% protein
• LDLs have apoprotein B-100 on their surface.

High-Density Lipoprotein (HDL)

• Also known as "good cholesterol"
• Synthesized in the intestine and liver cells
• HDL molecules are recycled from chylomicron and VLDL molecules
• Composed of 50% protein, 28% phospholipids, 19% cholesterol, and 3% triglycerides
• Has apoproteins A-I, mainly, and A-II on its surface

Lipoprotein (a) [Lp(a)]

• Primarily composed of cholesterol esters, phospholipids, and apolipoprotein (a) and B-100
• Elevated levels of Lp(a) are associated with increased risk for: • Coronary heart disease • Myocardial infarction • Cerebrovascular disease

Lipoprotein Physiology & Metabolism

• Lipoprotein metabolism involves the transport of lipids in the bloodstream, playing a crucial role in maintaining cellular lipid homeostasis.

Lipid Absorption

• Lipid absorption occurs in the small intestine, where dietary fats are broken down into fatty acids and cholesterol.
• Fatty acids are taken up by enterocytes, re-esterified into triglycerides, and packaged into chylomicrons.
• Chylomicrons are then transported to the lymphatic system, ultimately entering the bloodstream.

Endogenous Pathway

• The endogenous pathway involves the synthesis of lipids in the liver, which are then transported to peripheral tissues.
• The liver produces very-low-density lipoproteins (VLDLs), which are rich in triglycerides.
• VLDLs are converted into low-density lipoproteins (LDLs) in the bloodstream, which are then taken up by peripheral tissues.

Exogenous Pathway

• The exogenous pathway involves the uptake of dietary lipids from the small intestine, which are then transported to the liver.
• Chylomicrons are converted into chylomicron remnants in the bloodstream, which are then taken up by the liver.

Reverse Cholesterol Transport

• Reverse cholesterol transport is a process by which excess cholesterol from peripheral tissues is transported back to the liver for excretion.
• High-density lipoproteins (HDLs) play a crucial role in this process, taking up excess cholesterol from peripheral tissues and transporting it to the liver.
• The liver then excretes the cholesterol into the bile, which is eventually eliminated from the body.

Lipid Metabolism

• Lipid metabolism involves releasing fatty acids to cells for energy, then recycling glycerol into triglycerides.
• Enzymes involved in breaking down triglycerides include lipase, lipoprotein lipase, epinephrine, and cortisol.

Clinical Significance of Lipids

• Abnormal lipid metabolism can be due to genetic defects or can be acquired.
• Abnormal lipid metabolism is associated with an increased risk of coronary heart disease and other disorders.

ATP III Classification

• The National Cholesterol Education Program (NCEP) established the Adult Treatment Panel III Classification (ATP III).
• ATP III sets cutoff values for cholesterol and triglyceride levels based on a 9- to 12-hour fast.

Blood Disorders

• Hypoproteinemia: a condition characterized by very low protein levels in the blood
• Hyperlipoproteinemia: high levels of lipoproteins in the blood

Cholesterol-related Disorders

• Hypercholesterolemia: high cholesterol, characterized by increased levels of cholesterol in the blood
• Hypertriglyceridemia: high amounts of triglycerides in the blood

Combined Lipid Disorder

• Combined hyperlipidemia: elevated levels of fats in the blood, including low-density lipoprotein (LDL) cholesterol ("bad" cholesterol) and triglycerides

Dyslipidemia

• Abnormally high levels of lipids (fats) in the blood
• Typically asymptomatic, but can lead to cardiovascular diseases
• Can cause coronary artery disease, a common heart condition

Coronary Artery Disease

• Occurs when major blood vessels (coronary arteries) struggle to supply enough blood, oxygen, and nutrients to the heart muscle
• A common heart condition that can lead to cardiovascular disease

Peripheral Vascular Disease (PVD)

• A slow and progressive disorder of the blood vessels
• Caused by narrowing, blockage, or spasms in a blood vessel
• A type of cardiovascular disease

Cardiovascular Disease

• A class of diseases involving the heart or blood vessels
• May include conditions such as coronary artery disease, peripheral vascular disease, and arteriosclerosis

Arteriosclerosis

• Characterized by deposition of esterified cholesterol in the artery wall
• A type of cardiovascular disease that can lead to narrowing or blockage of blood vessels

Hypercholesterolemia and Familial Hypercholesterolemia

• Elevated cholesterol levels are associated with increased LDL (Low-Density Lipoprotein) due to genetic abnormalities.
• Despite normal intracellular cholesterol levels, individuals with Familial Hypercholesterolemia have a deficiency in active LDL receptors.

Hypertriglyceridemia

• Characterized by an imbalance between the synthesis and clearance of VLDL (Very-Low-Density Lipoprotein) in the circulation.
• Can be caused by familial or hormonal abnormalities.

Combined Hyperlipoproteinemia

• Characterized by elevated levels of serum total cholesterol and triglycerides
• Caused in part by excessive hepatic synthesis of apo B
• Leads to increased VLDL secretion
• Results in increased LDL production from VLDL
• Can be associated with Familial Dysbetalipoproteinemia

Familial Dysbetalipoproteinemia

• Caused by accumulation of cholesterol-rich VLDL and chylomicrons remnants

Lp(a) and its Impact on Plaque Formation

• Lp(a) is a variant of LDL (low-density lipoprotein) with an additional apolipoprotein (a)
• Apolipoprotein (a) has a high degree of homology with plasminogen, a coagulation factor
• Due to this homology, apo(a) competes with plasminogen for binding sites on fibrin
• This competition leads to increased plaque formation

Hypoalphalipoproteinemia

• Characterized by an isolated decrease in circulating high-density lipoprotein (HDL) cholesterol
• Defined as HDL levels less than 40 mg/dL or 1.0 mmol/L
• Not associated with hypertriglyceridemia
• Can result from mutations in genes involved in HDL metabolism
• Specifically, mutations in LCAT, apo A-I, and ABCA1 transporter genes can cause hypoalphalipoproteinemia

Tangier's Disease

• An extreme form of hypoalphalipoproteinemia
• Caused by mutations in the ABCA1 transporter gene

This quiz covers the composition and functions of lipids, including energy storage and hormone production, as well as the structure and properties of fatty acids. Learn about the role of lipids in living cells and their importance in human biology.