CC2 Flashcards
aka lipids
fats
Lipid composition
mostly carbon-hydrogen (C-H) bonds
Lipids are insoluble to:
blood (thus, requires transporter)
Lipids are soluble to:
organic solvents
Lipid transporter
Lipoproteins (VLDL, LDL, HDL)
Lipid classifications
- Fatty acids
- Triglycerides
- Cholesterol
- Phospholipids
- Fat soluble vitamins (A, D, E, K)
Lipid functions
- Primary source of fuel for cells
- Provides cell membrane stability
- Allows transmembrane transport
Linear chains of C-H bonds that terminates with -COOH (carboxyl grp)
Fatty Acids
Mostly found as constituent of phospholipids or TAG
Fatty Acids
Mainly derived from TAG hydrolysis in the adipose tissue
Fatty Acids
Important source of fuel/energy for cells
Fatty Acids
Provides a substance for lipid → glucose conversion (gluconeogenesis)
Fatty Acids
FA composition
Linear chains of C-H bonds that terminates with -COOH (carboxyl grp)
FA are mostly found as constituent of
phospholipids or TAG
FA is derived from
TAG hydrolysis in the adipose tissue
FA 3 classifications
BASED ON:
Presence of ester bonds
Length/no.
No. of double bonds
FA classification based on presence of ester bonds
Unesterified
Esterified
FA classification based on length/no.
Short
Medium
Long
FA classification based on no. of double bonds
Saturated
Monounsaturated
Polyunsaturated
Bound to albumin in the plasma
Unesterified fatty acids
Constituent of TAG or phospholipids
Esterified fatty acids
Length/no. of short fatty acids
4-6
Length/no. of medium fatty acids
8-12
Length/no. of long fatty acids
> 12
Fatty acid with no double bonds
Saturated
Fatty acid with 1 double bond
Monounsaturated
Fatty acid with 2 or more double bonds
Polyunsaturated
Examples of saturated fatty acids
Butyric acid
Stearic acid
Palmitic acid
Example of monounsaturated fatty acid
Oleic acid
Examples of polyunsaturated fatty acid
Linoleic acid
Arachidonic acid
3 fatty acids + 1 glycerol
Triglyceride
aka Triglyceride
Triacylglycerol,
Neutral fat
Contain saturated FA or unsaturated FA
Triglyceride
Hydrophobic, water insoluble: No charged or hydrophilic groups
Triglyceride
Predominant TAG form in plasma
Glyceryl ester
Main storage form of lipid in man
TAG
95% of storage fat; present in adipose tissue
TAG
Provide excellent insulation
TAG
TAG composition
3 fatty acids (saturated or unsaturated) + 1 glycerol
TAG hydrolysis
3 FA are released to the cells → FA is converted to energy
These 3 facilitates TAG hydrolysis:
- Lipoprotein lipase (LPL)
- Epinephrine
- Cortisol
2 fatty acids + glycerol
Phospholipids
aka Phospholipids
Conjugated lipid
3rd position of phospholipid structure
phospholipid head groups (PHOSPHORYLATION)
Formed from conjugation of 2 FA and phosphorylated glycerol
Amphipathic: hydrophilic (outer) and hydrophobic (inner) head groups
Phospholipids
Most abundant lipid in the body
Phospholipids
derived from phosphatidic acid
Phospholipids
Site of origin of phospholipids
liver
intestine
Lipid NOT routinely measured in the lab (low dx value)
Phospholipids
Participates in cell metabolism and blood coagulation
Phospholipids
Significant lipid in Amniotic fluid measurement
Phospholipids
Act as surfactants (alter fluid surface tension) during pregnancy
Phospholipids
Determines fetal lung maturity during 3rd trimester
Sphingomyelin / lecithin ratio
3 FORMS OF PHOSPHOLIPIDS
Lecithin (phosphatidylcholine)
Sphingomyelin
Cephalin
% IN TOTAL BODY PHOSPHOLIPID OF LECITHIN (PHOSPHATIDYLCHOLINE)
70% (highest)
% IN TOTAL BODY PHOSPHOLIPID OF SPHINGOMYELIN
20%
% IN TOTAL BODY PHOSPHOLIPID OF CEPHALIN
10% (lowest)
Other examples of phospholipids
Phosphatidylserine
Phosphatidylethanolamine
Phosphatidylcholine (lecithin)
Unsaturated steroid alcohol contains 4 rings, component of steroids
Cholesterol
Phospholipid composition
2 fatty acids + glycerol
3rd position: phospholipid head groups
Single C-H side chain tail, similar to FA
Cholesterol
aka Cholesterol
3-hydroxy-5,6-cholestene
T/F
Cholesterol is amphipathic
T
Precursor for the assembly of cell membrane and bile acids
Cholesterol
NOT metabolized by most cells (not a fuel source)
Cholesterol
What happens to unmetabolized cholesterol?
recycled back to the liver
Cholesterol is converted to:
Bile salts
Steroid hormones
Vitamin D (Ca absorption) and cell membrane
Production of bile salts
liver
Storage of bile salts
gallbladder
Promote fat absorption in the intestine
Bile salts
Examples of steroid hormones from conversion of cholesterol
glucocorticoids
mineralocorticoid
estrogen
Cholesterol classification
Unesterified (Free cholesterol)
Esterified (Cholesterol ester)
Unesterified type of cholesterol
Free cholesterol
(amphipathic)
Esterified type of cholesterol
Cholesterol ester
(neutral lipid)
% in total chole of Free cholesterol
30%
% in total chole of Cholesterol ester
70%
Location of Free cholesterol
Plasma,
Serum,
RBC
Location of Cholesterol ester
Plasma,
Serum
Polar form (hydrophilic) cholesterol
Free cholesterol (unesterified)
Nonpolar form (hydrophobic) cholesterol
Cholesterol ester
T/F
Cholesterol types are measured individually in the laboratory.
F
Both are measured in the laboratory as TOTAL CHOLESTEROL
Enzyme for esterification
Lecithin Cholesterol Acyl Transferase (LCAT)
T/F
Lecithin Cholesterol Acyl Transferase (LCAT) is not normally present
F
Normally present
Site of synthesis of LCAT
Liver
Promotes FA transfer from lecithin to chole →
products: lysolecithin + cholesterol esters
Lecithin Cholesterol Acyl Transferase (LCAT)
Activator of Lecithin Cholesterol Acyl Transferase (LCAT)
Apo A1
Products when LCAT promotes FA transfer from lecithin to chole
lysolecithin + cholesterol esters
Used to transport lipids
LIPOPROTEIN
Composed of both lipids and proteins
LIPOPROTEIN
Protein part of LPP
apolipoprotein
T/F
In lipoproteins, density depends on the protein constituent
T
APOLIPOPROTEIN FUNCTIONS
✓ Maintain structural integrity
✓ Ligands for cell receptor
✓ Activators and inhibitors of enzymes
T/F
Apolipoproteins are amphipathic
T
Composition of lipoprotein
Free cholesterol (surface)
Phospholipids (surface)
TAG (core)
Cholesteryl esters (core)
Found on the SURFACE of apolipoprotein
Free cholesterol
Phospholipids
Found on the CORE of apolipoprotein
TAG
Cholesteryl esters
MAJOR LIPOPROTEIN TYPES
Chylomicrons
VLDL
LDL
HDL
Largest to smallest lipoproteins
Chylomicrons (largest)
VLDL
LDL
HDL (smallest)
Least dense (↓ protein) to Most dense (↑ protein)
Chylomicrons
VLDL
LDL
HDL
Major LPP Location:
Apo A-1
HDL
Major LPP Location:
Apo A-II
HDL
Major LPP Location:
Apo A-IV
CM, VLDL, HDL
Major LPP Location:
Apo B-100
LDL, VLDL
Major LPP Location:
Apo B-48
CM
Major LPP Location:
Apo C-I
CM, VLDL, HDL
Major LPP Location:
Apo C-II
CM, VLDL, HDL
Major LPP Location:
Apo C-III
CM, VLDL, HDL
Major LPP Location:
Apo E
VLDL, HDL
Major LPP Location:
Apo(a)
Lp (a)
Apolipoprotein with major location is HDL
Apo A-I
Apo A-II
Apo A-IV
Apo C-I
Apo C-II
Apo C-III
Apo E
Apolipoprotein with major location is Chylomicron
Apo A-IV
Apo B-48
Apo C-I
Apo C-II
Apo C-III
Apolipoprotein with major location is VLDL
Apo A-IV
Apo B-100
Apo C-I
Apo C-II
Apo C-III
Apo E
LCAT activator, ABCA1 lipid acceptor
Apo A-I
LCAT inactivator
Apo A-II
LDL receptor ligand
Apo B-100
Apo E
Remnant receptor ligand
Apo B-48
LPL cofactor
Apo C-II
LPL inhibitor
Apo C-III
Plasminogen inhibitor
Apo(a)
Least dense (2% protein) lipoprotein
Chylomicrons
Most dense (50% protein) lipoprotein
HDL
Largest lipoprotein
Chylomicron
Smallest lipoprotein
HDL
Lipoprotein with highest lipid content
Chylomicrons
Lipoprotein with smallest lipid content
HDL
Most TAG rich lipoprotein
Chylomicron
Lipoprotein with least TAG content
HDL
Most cholesterol rich lipoprotein
LDL
Lipoprotein with least cholesterol content
Chylomicrons
Conversion Factor (mmol/L) for TOTAL CHOLESTEROL
0.026
Conversion Factor (mmol/L) for TAG
0.011
Reference range (mg/dL)
Total cholesterol =
HDL cholesterol =
LDL cholesterol =
TAG =
Total cholesterol = 140-200
HDL cholesterol = 40-75
LDL cholesterol = 50-130
TAG = 60-150
aka Pre-β lipoprotein
VLDL
aka β lipoprotein
LDL
aka Bad cholesterol
LDL
aka α lipoprotein
HDL
aka good cholesterol
HDL
Largest, least dense lipoprotein
Chylomicrons
Lipoprotein completely cleared in the circulation within 6-9 hrs after eating
CHYLOMICRONS
Float in the middle of serum → homogenous turbidity (before and after overnight standing)
VLDL
Most atherogenic lipoprotein (initiates formation of fatty plaque in BV)
LDL
Cardioprotective lipoprotein
HDL
Site of CHYLOMICRON production
Intestine
Site of VLDL production
Liver
Production of LDL
VLDL lipolysis to IDL → LDL
Site of HDL production
Liver
Intestine
Delivers dietary lipids (exogenous TAG) to hepatic and peripheral cells
CHYLOMICRONS
Transfers endogenous TAG from the liver to peripheral tissue
VLDL
Transfers dietary cholesterol to peripheral tissue
LDL
Transfer excess cholesterol from peripheral cells back to the liver
HDL
MINOR LIPOPROTEIN TYPES
LIPOPROTEIN(a)
INTERMEDIATE DENSITY LPP (IDL)
ABNORMAL LIPOPROTEINS
LIPOPROTEIN X
B-VLDL (floating β lipoprotein)
aka Sinking pre-β lipoprotein
LIPOPROTEIN(a)
LDL lipoprotein-like particle
LIPOPROTEIN(a)
Has similar structure to plasminogen
LIPOPROTEIN(a)
↑ Lp(a) confers ↑ risk for:
o Premature CHD
o Stroke
Competes with plasminogen for fibrin
Lp(a)
Mechanism of premature CHD
MECHANISM: Competition with plasminogen for fibrin
Clot formation will prevent further blood loss. When bleeding is controlled due to clot → damaged BV undergoes repair → clot removed through fibrinolysis.
Plasminogen promotes fibrinolysis. In presence of Lp(a), it will compete with plasminogen (Lp(a) – acts as inhibitor of plasminogen). Fibrin clot will not be dissolved, accumulates and adds up in the fatty flakes in the blood vessels → early manifestation of CHD
VLDL remnant: 1st product of VLDL catabolism
INTERMEDIATE DENSITY LPP (IDL)
VLDL → IDL → LDL
Subclass of LDL
INTERMEDIATE DENSITY LPP (IDL)
Migration of Lp(a)
Variable
* pre-β
* between LDL &
albumin
(Migrates with VLDL)
Minor lipoprotein that migrates with VLDL
LIPOPROTEIN(a)
Migration is either pre-β or β region
INTERMEDIATE DENSITY LPP (IDL)
Minor lipoprotein with a density similar to LDL
LIPOPROTEIN(a)
Specific and sensitive indicator of cholestasis
LIPOPROTEIN X
Abnormal lipoprotein found in obstructive jaundice and LCAT deficiency
LIPOPROTEIN X
MAJOR LIPID CONTENT OF LIPOPROTEIN X
Phospholipid & Free cholesterol (90%)
PROTEIN FRACTION OF LIPOPROTEIN X
Apo C
Albumin
aka Abnormally migrating β-VLDL
B-VLDL (floating β lipoprotein)
Lipoprotein found in type 3 hyperlipoproteinemia or dysbetalipoproteinemia
B-VLDL (floating β lipoprotein)
Rich in cholesterol than VLDL
B-VLDL (floating β lipoprotein)
Has a defective VLDL catabolism (failure to convert VLDL to LDL causing IDL accumulation)
B-VLDL (floating β lipoprotein)
Migration of LIPOPROTEIN X
Towards cathode
(unique, since all LPP
migrates toward anode)
Migration of B-VLDL (floating β
lipoprotein)
β region
(Migrates with LDL)
LIPOPROTEIN(a) migration
Variable:
* pre-β
* between LDL &
albumin
(Migrates with VLDL)
IDL migration
Either pre-β or β region
Density is similar to VLDL by ultracentrifugation
B-VLDL (floating β lipoprotein)
Lipoprotein metabolism
- Lipid Absorption
- Exogenous Pathway
- Endogenous Pathway
- Reverse Cholesterol Transport Pathway
Conversion of dietary lipids into more
polar/absorbable (amphipathic) compounds by
PANCREATIC LIPASE
LIPID ABSORPTION
Enhanced by emulsifying agents (bile salts)
LIPID ABSORPTION
Site of occurrence of LIPID ABSORPTION
Small intestine
Converted in LIPID ABSORPTION
Dietary lipids
ENZYME in LIPID ABSORPTION
Pancreatic lipase
Products in LIPID ABSORPTION
More polar/absorbable (amphipathic) compound
Triglyceride → Monoglycerides
Cholesterol esters → Free cholesterol
Phospholipids → Lysophospholipids
Chylomicrons transports exogenous dietary lipids (TAG) from the intestine to the liver and circulation (peripheral cells)
In the liver: LPL hydrolyzes TAG in CM into FA & glycerol or re-esterified for long term storage
Converts CM → CM remnant particles
EXOGENOUS PATHWAY
MEDIATOR in EXOGENOUS PATHWAY
Chylomicrons (synthesized in
the intestine)
Absorbed dietary lipids are transported by CM from intestine to the circulation which makes lipemic plasma
SITE OF OCCURRENCE OF . EXOGENOUS PATHWAY
Intestine
↓
Liver & Circulation
(peripheral cells)
CONVERTED IN EXOGENOUS PATHWAY
Dietary lipids (TAG)
(exogenous)
ENZYME IN EXOGENOUS PATHWAY
Lipoprotein lipase (LPL)
PRODUCTS IN EXOGENOUS PATHWAY
TAG in CM → Fatty acids & glycerol or
→ Re-esterified for long
term storage in hepatic
cells
CM → CM remnant particles
TAG in the liver (endogenous) is packaged into VLDL, carrying lipids to the circulation
ENDOGENOUS PATHWAY
MEDIATOR OF ENDOGENOUS PATHWAY
VLDL
LDL
SITE OF OCCURRENCE OF ENDOGENOUS PATHWAY
Circulation
(peripheral cells)
CONVERTED/CARRIED IN ENDOGENOUS PATHWAY
TAG in the liver
(endogenous)
ENZYME IN ENDOGENOUS PATHWAY
Lipoprotein lipase (LPL)
PRODUCTS IN ENDOGENOUS PATHWAY
VLDL carrying endogenous TAG:
→ 50%: VLDL remnants by LPL → taken up by liver
→ 50%: LDL → delivers of exogenous cholesterol to peripheral cells
HDL remove excess cholesterol in circulation → liver
REVERSE CHOLESTEROL TRANSPORT PATHWAY
MEDIATOR IN REVERSE CHOLESTEROL TRANSPORT PATHWAY
HDL
SITE OF OCCURENCE OF REVERSE CHOLESTEROL TRANSPORT PATHWAY
Circulation
(peripheral cells)
↓
Liver
(for excretion)
CONVERTED/CARRIED IN REVERSE CHOLESTEROL TRANSPORT PATHWAY
Excess cholesterol
LIPID DISORDERS
- Arteriosclerosis
- Hyperlipoproteinemia
o Hypercholesterolenemia
o Hypertriglyceridemia
o Combined hyperlipidemia - Hypolipoproteinemia
- Lp(a) elevation
Deposition of esterified cholesterol (hydrophobic), in artery walls
ARTERIOSCLEROSIS
lipoprotein indicator of inc. esterified chole in the blood
LDL
Increased fats + insoluble components → smooth muscle cells, extracellular lipid, calcification, fibrous tissue, macrophages, lymphocytes and platelets (fatty plaque)
ARTERIOSCLEROSIS
Thrombosis (blocks circulation): caused by rupture/erosion
ARTERIOSCLEROSIS
Conditions under ARTERIOSCLEROSIS and their affected sites
Coronary artery disease (CAD): heart (angina, MI)
Peripheral vascular disease (PVD): arteries in arms or legs
Cerebrovascular disease (CVD): brain vessels (stroke)
Under HYPERLIPOPROTEINEMIA
Hypercholesterolenemia
Hypertriglyceridemia
Combined Hyperlipoproteinemia
↑ Cholesterol
↑ LDL, ↓ receptors
Hypercholesterolenemia
↑ TAG
↓ LPL or APO C-II
VLDL → VLDL remnants
CM → CM remnants
Hypertriglyceridemia
↑ TAG, Cholesterol
↑ VLDL and CM remnants
APO E2/2
Combined Hyperlipoproteinemia
OTHER LIPID DISORDERS
- Familial Hypercholesterolemia (Type 2a)
- Familial Dysbetalipoproteinemia (Type 3 hyperlipoproteinemia)
- Abetalipoproteinemia (Basses-Kornzweig Syndrome)
- Hypobetalipoproteinemia
- Niemann-Pick Disease (Lipid Storage Disease)
- Tangier’s Disease
- Lipoprotein Lipase (LPL) Deficiency
- LCAT Deficiency
- Tay-Sachs Disease
Contained when a tube of turbid plasma is left overnight in a refrigerator
at 4ºC and became lipemic
CHYLOMICRONS
VLDL
Phospholipids are derived from
Phosphatidic acid
What is determined in Sphingomyelin / lecithin ratio?
Fetal lung maturity during 3rd trimester
B-VLDL (floating β lipoprotein) is found in these conditions
Type 3 hyperlipoproteinemia
Dysbetalipoproteinemia
aka Familial Hypercholesterolemia
Type 2a
aka Familial Dysbetalipoproteinemia
Type 3 hyperlipoproteinemia
aka Abetalipoproteinemia
Basses-Kornzweig Syndrome
aka Niemann-Pick Disease
Lipid Storage Disease
