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Lipids and lipid disorders

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107 Questions

What is the primary function of lipids in living cells?

Energy storage for excess calories

What is the characteristic of fatty acids in plasma?

Non-covalently bound to albumin

What is a precursor to steroid hormones?

Lipids

What is the characteristic of the bonds in lipids?

Mostly C-H bonds

What are some of the biomolecules that lipids can be converted to?

Prostaglandins, leukotrienes, and lipoxins

What is the typical carbon atom count of short-chain fatty acids?

4 to 6

What type of fatty acid has a carbon atom count of more than 12?

Long-chain

Which type of fatty acid is bound to albumin?

Unesterified

What is a characteristic of esterified fatty acids?

Part of triglycerides or phospholipids

What is the main difference between medium-chain and long-chain fatty acids?

Their carbon atom count

What type of fatty acid has no double bonds?

Saturated

How many fatty acids are attached to a molecule of glycerol in a triglyceride?

3

What is the characteristic of triglycerides in terms of their charge?

Neutral

What type of bond holds the fatty acids to the glycerol molecule in a triglyceride?

Ester bond

What is the characteristic of triglycerides in terms of their solubility in water?

Insoluble in water

What is the number of fatty acids attached to a molecule of glycerol in a phospholipid?

2

What is the characteristic of the head and tails of phospholipids?

Hydrophobic head and hydrophilic tails

What is the structure of cholesterol?

A 4-ring unsaturated steroid

What is the characteristic of phospholipids and cholesterol?

Both are amphipathic

What is the location of the phospholipid head group?

3rd position

Synthesized from acetyl co-A

CHOLESTEROL

What is the range of size of lipoproteins?

10-1200 nm

What is the composition of lipoproteins?

Lipids and proteins

What is the term for unesterified cholesterol?

Free cholesterol

What is the term for esterified cholesterol?

Cholesteryl ester

What shape are lipoproteins typically?

Spherical

What is the main apoprotein found on the surface of chylomicrons?

Apo B-48

What percentage of chylomicrons are composed of triglycerides?

86%

What is the characteristic of chylomicrons when plasma is stored overnight?

They float to the top and form a creamy layer

What is the percentage of phospholipid in chylomicrons?

7%

What is the function of chylomicrons in the body?

To transport triglycerides after a meal

What percentage of triglycerides are present in VLDL molecules?

55%

Which apolipoprotein is mainly present on the surface of VLDL molecules?

Apolipoprotein B-100

Where are VLDL molecules secreted into the blood from?

The liver

What percentage of phospholipid is present in VLDL molecules?

18%

What is the purpose of VLDL molecules in normal lipid metabolism?

To transport endogenous triglycerides to peripheral tissues

What percentage of triglycerides are present in IDL molecules?

23%

What is the main apolipoprotein present on the surface of IDL molecules?

Apolipoprotein B-100

What is the percentage of cholesterol in IDL molecules?

38%

What is the percentage of phospholipid in IDL molecules?

19%

What is formed from IDL molecules after modification in the liver?

LDL molecules

What percentage of LDL is composed of cholesterol?

50%

What is the main function of LDL in the body?

To transport a large amount of endogenous cholesterol

What is the composition of LDL?

50% cholesterol, 22% phospholipids, 6% triglycerides, and 22% protein

What is present on the surface of LDL molecules?

Apoprotein B-100

What is the consequence of elevated levels of LDL in the body?

Increased risk for atherosclerosis

What is the primary site of HDL synthesis?

Intestine and liver cells

What is the main apoprotein present on the surface of HDL molecules?

ApoA-I

What is the percentage of cholesterol in HDL molecules?

19%

What is HDL composed of?

50% protein, 28% phospholipids, 19% cholesterol, and 3% triglycerides

What are HDL molecules formed from?

Recycled chylomicron and VLDL molecules

What is Lp(a) primarily composed of?

Cholesterol esters, phospholipids, and apolipoprotein (a) and B-100

What is associated with elevated levels of Lp(a)?

Increased risk for coronary heart disease, myocardial infarction, and cerebrovascular disease

What is the significance of Lp(a) in the body?

It is associated with increased risk of cardiovascular disease

What apolipoprotein is present in Lp(a)?

Apolipoprotein B-100

What is the composition of Lp(a) lipoprotein?

Cholesterol esters, phospholipids, and apolipoprotein (a) and B-100

What are the two main pathways involved in lipoprotein physiology and metabolism?

Lipid absorption reverse cholesterol pathways Endogenous and exogenous pathways

What is the role of lipase, lipoprotein lipase, epinephrine, and cortisol in lipid metabolism?

To break down triglycerides

What is the consequence of abnormal lipid metabolism?

Increased risk of coronary heart disease

What is the purpose of the ATP III Classification?

To set cutoff values for cholesterol and triglyceride levels

What is the result of recycling glycerol in lipid metabolism?

The formation of triglycerides

What is the relationship between lipid metabolism and coronary heart disease?

Abnormal lipid metabolism is associated with an increased risk of coronary heart disease

What is hypercholesterolemia characterized by?

Increased levels of cholesterol in the blood

What is combined hyperlipidemia characterized by?

Elevated levels of fats in the blood, including LDL cholesterol and triglycerides

What is hypertriglyceridemia characterized by?

High levels of triglycerides in the blood

What is hypoproteinemia characterized by?

Very low protein levels in the blood

Which condition is characterized by high levels of lipoproteins in the blood?

Hyperlipoproteinemia

What is the term for abnormally high levels of lipids in the blood?

Dyslipidemia

What is the term for the narrowing, blockage, or spasms in a blood vessel?

Peripheral vascular disease (PVD)

What is the deposition of esterified cholesterol in the artery wall known as?

Arteriosclerosis

What is the term for the class of diseases that involve the heart or blood vessels?

Cardiovascular disease

What is the term for a common heart condition where the coronary arteries struggle to send enough blood, oxygen, and nutrients to the heart muscle?

Coronary artery disease

What is the primary cause of elevated cholesterol in Familial Hypercholesterolemia?

Genetic abnormalities affecting LDL receptors

What is the characteristic of intracellular cholesterol in Familial Hypercholesterolemia?

Normal

What is Hypertriglyceridemia a result of?

Imbalance between synthesis and clearance of VLDL in the circulation

What is the consequence of elevated levels of LDL in the body?

Increased risk of cardiovascular disease

What is the primary difference between Familial Hypercholesterolemia and Hypertriglyceridemia?

One is caused by LDL receptor defects, the other by VLDL imbalance

What is responsible for the excessive hepatic synthesis of apo B, leading to increased VLDL secretion and LDL production?

Combined Hyperlipoproteinemia

What is the result of excessive hepatic synthesis of apo B in Combined Hyperlipoproteinemia?

Increased VLDL secretion and LDL production

What is the characteristic of Familial dysbetalipoproteinemia?

Accumulation of cholesterol-rich VLDL and chylomicrons remnants

What is the result of the accumulation of cholesterol-rich VLDL and chylomicrons remnants in Familial dysbetalipoproteinemia?

Elevated levels of serum total cholesterol and triglycerides

What is the underlying cause of Combined Hyperlipoproteinemia?

Excessive hepatic synthesis of apo B

What is characteristic of Lp(a)?

It is a variant of LDL with an extra apolipoprotein (a)

What does apolipoprotein (a) in Lp(a) compete with for binding sites?

Plasminogen

What is the effect of Lp(a) on plaque formation?

It increases plaque formation

What is the consequence of elevated levels of Lp(a)?

It increases the risk of cardiovascular disease

What is the role of apolipoprotein (a) in Lp(a)?

It competes with plasminogen for fibrin binding sites

What is hypoalphalipoproteinemia characterized by?

Isolated decreased in circulating HDL (< 40 mg/dL or 1.0 mmol/L) without hypertriglyceridemia

What mutations are associated with hypoalphalipoproteinemia?

Mutations in LCAT, apo A-I and ABCA1 transporter gene

What is Tangier's disease?

An extreme form of hypoalphalipoproteinemia

What is the typical circulating HDL level in hypoalphalipoproteinemia?

< 40 mg/dL or 1.0 mmol/L

What is the underlying genetic defect in hypoalphalipoproteinemia?

All of the above

What is the normal reference range for triglycerides in the blood?

< 150 mg/dL

What is the borderline high for triglyceride reference range?

150-199 mg/dL

What is high for triglyceride reference range?

200-499 mg/dL

What is the very high reference range for triglyceride levels?

≥500 mg/dL

What is the optimal reference range for LDL Cholesterol?

Less than 100 mg/dL

What is the near optimal reference range for LDL cholesterol?

100-129 mg/dl

What is the borderline high reference range for LDL cholesterol?

130-159 mg/dl

What is the high reference range for LDL cholesterol?

160-189 mg/dL

What is the very high reference range for LDL cholesterol?

190 mg/dL or higher

What is the near protective against heart disease range for HDL cholesterol reference range?

≥60 mg/dL

What is the higher the better range for HDL cholesterol reference range?

40-59 mg/dL

What is the major risk factor for heart disease range for HDL cholesterol reference range?

Below 40 mg/dL

What is the desirable range for total cholesterol reference range?

below 200 mg/dL

What is the borderline high range for total cholesterol in the reference range?

200-239 mg/dL

What is the high range for total cholesterol reference range?

≥ 240 mg/dL

Study Notes

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.

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