6) Lipids & lipoproteins Flashcards
4 lipid functions
- Main source of energy and energy storage
- Converted to hormones or hormone precursors
- Serve as structural and functional components of cell membranes
- Provide insulation for nerve conduction and heat retention
5 lipid classes
- Sterol derivatives
- Fatty acids
- Glycerol esters
- Sphingosine derivatives
- Terpenes
4 sterol derivatives
- Cholesterol and cholesteryl esters
- Steroid hormones
- Bile acids
- Vitamin D
3 size classifications of FAs
Short chain (2-4 C atoms)
Medium chain (6-10 C atoms)
Long chain (12-26 C atoms)
terpenes
Vitamin A
Vitamin E
Vitamin K
Contains 27 carbon atoms and four fused rings (A, B, C, and D) called the perhydrocyclopentanophenanthrene nucleus.
cholesterol
3 main functions of cholesterol
- Structural component of cell membranes
- Precursor of bile acids
- Precursor of Vitamin D and steroid hormones
2 forms of cholesterol
exogenous
endogenous
Cholesterol is solubilized by the formation of mixed ——-
micelles
If the amount of cholesterol ….. then a supersaturated state can occur that results in the formation of gallstones
exceeds the capacity of solubilizing agents
FA nomenclature
methyl end = omega end
number for double bond position
Derivatives of fatty acids comprising 20 C atoms, including a five-carbon cyclopentane ring
prostaglandins
4 functions of prostaglandins
- Contraction and relaxation of smooth muscle
- Dilation and constriction of blood vessels
- Control of blood pressure
- Modulation of inflammation
comprise 95% of fat stored in tissue
TGs
lecithins
phospholipids
Important component of the myelin sheath
sphingomyelin
5 components of a lipoprotein
- An outer layer of proteins
- Apolipoproteins
- Polar lipids (phospholipids)
- Unesterified cholesterol
- An inner core of neutral lipids (phospholipids and esterified cholesterol).
These are receptor sites or the “address tags” to tell the lipoprotein where to go in the body
apolipoproteins
Form the major proteins in HDL and in chylomicrons
Apo-A
This is the major protein for LDL and VLDL. This binds LDL to LDL receptors.
Apo-B
This lipoprotein helps in metabolism of triglyceride rich lipoproteins
Apo-C
This lipoprotein may function as a transfer protein to assist in the movement of cholesterol and triglycerides between LDL and HDL.
Apo-D
Important in recognition and catabolism of chylomicrons and remnant IDL.
Apo-E
4 pathways of lipoprotein metabolism
Lipid absorption
Exogenous
Endogenous
Reverse cholesterol
Triglycerides: 84%
Apolipoproteins: 1–2%
Cholesterol: 7%
Phospholipids: 6%
chylomicrons
Triglycerides: 44–60%
Cholesterol: 16–22%
Apolipoproteins: 2–8%
Phospholipids: 18%
VLDL
Triglycerides: 25%
Cholesterol: 38%
Apolipoproteins: 11%
Phospholipids: 26%
IDL
Triglycerides: 11%
Cholesterol: 62%
Apolipoproteins: 20%
Phospholipids: 23%
LDL
Triglycerides: 3%
Cholesterol: 19%
Apolipoproteins: 50%
Phospholipids: 25–30%
HDL
short vs long chain FA transportation
Short-chains are carried by albumin to the liver
Long-chains are packaged into chylomicrons
Composed of the metabolism of chylomicrons
Responsible for transporting dietary or exogenous fat, mostly triglycerides, from the intestines to the liver and peripheral cells
exogenous pathway
chylomicron plasma appearance
turbid
creamy layer after ultracentrifuge or sitting at RT
chylomicron Apo
Apo A
Apo B-48
Apo C-II
Apo E
Involves the metabolism of very-low-density lipoproteins (VLDL) to intermediate density lipoproteins (IDL) to low-density lipoproteins (LDL)
endogenous pathway
VLDL plasma appearance
turbid
no creamy layer after ultracentrifugation
VLDL Apo
Apo B-100
Apo C-II
Apo E
Can be elevated in patients with type III hyperlipoproteinemia, a rare inborn error of metabolism
IDL
IDL Apo
Apo B-100
Apo E
IDL function
Transports triglycerides and cholesterol to the liver from peripheral tissues.
LDL function
Major transporter of cholesterol in plasma to peripheral tissues
LDL Apo
Apo B-100
HDL function
reverse cholesterol transport
Cholesterol scavenger that removes cholesterol from tissues and carries it to the liver for disposal
HDL Apo
Apo A-I
Apo C-II
Apo E
Independent, causal risk factor for atherosclerosis
Highly heritable
Lipoprotein (a)
LipoProtein Lipase (LPL) Deficiency
I. Familial Hyperchylomicronemia
LDL Receptor Mutations
(Deficiency)
ApoB-100 Mutations
IIa. Familial
Hypercholesterolemia
LDL Receptor Mutations
Overproduction of VLDL and ApoB-100
IIb. Familial Combined Hyperlipidemia.
ApoE Deficiency
(Abnormal IDL metabolism)
III. Familial
dys-beta-lipoproteinemia
Overproduction of VLDL
IV. Familial Hypertriglyceridemia
Abnormal VLDL & chylomicron metabolism
V. Familial mixed Hypertriglyceridemia
Has been associated with hyperthyroidism and hepatocellular disease
Malnutrition, starvation, and eating disorders (anorexia, bulimia)
abetalipoproteinemia
hypocholesterolemia
Associated with acute pancreatitis as both a precipitant and an epiphenomenon
hypertriglyceridemia
A very rare condition that affects fat and vitamin absorption by the intestines and liver, leading to very low LDL-cholesterol and malnutrition.
abetalipoproteinemia
enzymes used in cholesterol methodology
cholesterol esterase
cholesterol oxidase
Classic method and can separate/fractionate all lipoproteins
Analytical ultracentrifugation
Heparin-manganese-chloride (method of choice)
Dextran sulfate-magnesium chloride
Sodium phosphotungstate Mg2+
used in selective precipitation
HDL left in solution
Uses an antibody to Apo B-100 to bind LDL and VLDL.
Homogenous enzyme assays
(block non-HDL)
Friedewald formula for indirect LDL
LDL = total cholesterol - (HDL + TG/5)
TG/5 = VLDL
cannot use indirect LDL method if…
TG level is over 400 mg/dL
High amount of chylomicrons
Dysbetalipoproteinemia
TG methodologies use enzyme…
lipase
Group of interrelated metabolic risk factors that appear to directly promote the development of atherosclerotic cardiovascular disease
metabolic syndrome
criteria for metabolic syndrome
Must have 3:
- Increased waist circumference (>40 in men; >35 in women)
- Elevated triglycerides (>150 mg/dL; or on TG meds)
- Low HDL-C (<40 mg/dL men; <50 mg/dL women; or on HDL meds)
- Elevated blood pressure (>130/85; or on HTN meds)
- Elevated fasting glucose (>100 mg/dL; or on DM meds)
