Lipids Flashcards
Defined as biosynthesis of fatty acid
Lipogenesis
Three types of lipogenic pathways based on cellular localization
Extramitochondrial
Microsomal
Mitochondrial
Extramitochondrial lipogenesis pathway occurs in
Cytosol
Microsomal lipogenesis pathway occurs in
Smooth endoplasmic reticulum
Mitochondrial lipogenesis pathway occurs in
Mitochondrion
General principle of lipogenesis is
Add 2 carbon atoms per cycle
Takes place in the cytosol
Conversion of acetyl CoA to malonyl CoA via acetyl CoA carboxylase is the rate limiting step
Uses biotin
Extramitochondrial lipogenesis
In the extramitochondrial lipogenesis pathway, Acetyl CoA is converted to
*rate-limiting step
malonyl CoA
Is the rate-limiting step or committed enzyme in extramitochondrial lipogenesis
Acetyl CoA Carboxylase
Prosthetic group of Acetyl CoA
Biotin
Acetyl CoA carboxylase for conversion of acetyl coa to malonyl coa is inhibited by
palmitic acid
A protein found in raw egg white, inhibits the committed step by binding and removing biotin
Avidin to acetyl carboxylase
Energy source per gram of lipid
9 calories
Adipose ->
Fatty acids -> CO2 + H2O + ATP
Major components of cell membranes
Phosphoglycerides
Sphingolipids
Cholesterol
Lipid classes
Fatty acid derivatives Triacylglycerol (TAG) Phospholipids Sphingolipids Wax esters Isoprenoids (terpenes, steroids) Lipoproteins
2-4 carbon atom Fatty acids
Short
6-10 carbon atom fatty acid
Medium
12-26 carbon atom or more fatty acid
Long
Have only single bonds in hydrocarbon chain
Saturated fatty acid
Are solids at room temperature because the regular nature of their aliphatic chains allows the molecules to be packed in close, parallel alignment
Have only single bonds in hydrocarbon chain
Saturated fatty acids
Have at least one C = C double bond in the chains
In contrast, are all liquid at room temperature because the cis double bonds interrupt the packing of the chains
Thus less energy is required to melt them
Unsaturated fatty acids
The greater the degree of unsaturation,
the lower the melting point
20 Carbon Double-Bonds with Methyl, Oil soluble OMEGA end and a Carboxyl, Water-soluble Delta End
Eicosapenaenoic acid (EPA) Omega 3
22 Carbon Double-Bonds with Methyl, Oil-soluble, Omega End and Carboxyl, Water-Soluble Delta End
Docasahexaenoic Acid (DHA) Omega 3
18 Carbon Double-Bonds with Methyl, Oil-soluble Omega end and Carboxyl, Water-Soluble Delta end
Gamma-linolenic Acid (GLA)
Omega 6
20 Carbon Double-bonds with Methyl, Oil-Soluble Omega End and Carboxyl, Water-Soluble Delta End
Dihomo-gamma-linolenic Acid (DGLA)
Omega 6
Polyunsaturated >2 double bonds
Not synthesized by body
Decrease risk of Cardiovascular Disease
Polyenoic fatty acids
Essential fatty acids
Omega 3
Omega 6
C18 having two double bonds
Linoleic acid
Lady linoleic linolenic
C18 having three
Precursor of EPA (eicosapentaenoic acid) and DHA (docosahexanoic acid)
Linolenic acid
C20 having four double bonds
Arachidonic acid
The main storage forms of fatty acids
The acylglycerols are esters of fatty acids bound to the sugar alcohol glycerol
All three OH groups of glycerol are esterified
They are the most common lipid material
TAG
They are also called neutral fats, because the carboxyl groups of the fatty acids are bound in ester linkage and can no longer function as acids
Mixtures are referred to as fats or oils
TAG
Molecules are classified according to which alcohol becomes esterified to the phosphate group
Phosphoglyceride
Phosphatidylcholine (PC or Lecithin) Phosphatidylethanolamine Phosphatidylserine Diphosphatidylglycerol Phosphatidylinositol
Phosphoglyceride
Surfactants or surface-acting agents
Plays an essential role in reducing surface tension in lung alveoli
Increase pulmonary compliance
Respiratory Distress Syndrome of the newborn
Lecithin
Phosphatidylcholine
Serologic test for syphilis
Utilizes a diphosphatidylglycerol as the antigen
Venereal Disease Research Laboratory
Cardiolipin
With repeating 5-carbon units (isoprene)
Terpenes
Steroids
Isoprenoids
Mixed terpenoids
Vitamin E (alpha tocopherol) Ubiquinone Vitamin K
Complex derivatives of triterpenes
All with 4 fused rings
The essential structural nucleus of the steroids consists of three fused cyclohexane rings joined to a cyclyopentene ring
Steroids
Ovarian steroid
estrogen
18 Carbon atoms
The A ring of the steroid nucleus of estrogen is aromatic
Estrogen
Has OH groups attached to carbons 3 and 17
Estradiol
Produced in the adrenal cortex and the testes
19 Carbon atoms
Testosterone
Dehydroepiandrosterone
Androgens
One of the more potent androgen
Testosterone
Unlike testosterone is a 17-ketosteroid
Dehydroepiandrosterone (DHA)
Synthesized in the corpus luteum
Has 21 carbons
Progesterone
A potent glucocorticoid with weak mineralocorticoid activity
Cortisol
Is a potent mineralocorticoid but a weak glucocorticoid
Aldosterone
This assay detects all 21-carbon steroids with a 17-OH group, such as cortisol
Urinary 17-hydroxycorticosteroid
Lipids must bind to proteins to make them water-soluble for transport in the blood
Lipoproteins
Are the least dense lipoproteins
After a fatty meal, the blood appears milky due to the high concentration of chylomicrons
Chlyomicrons
An anticoagulant also helps to clear chylomicrons from the blood, perhaps by stimulating lipoprotein lipase
Heparin
The inherited absence of lipoprotein lipase causes
Hyperchlyomicronemia
Frederickson’s type I hyperlipoproteinemia
Contain principally triglycerides, but have a greater protein, phospholipid, and cholesterol content than chylomicrons
Their protein and phospholipid content makes them charged so that they migrate just before the B-globulins in electrophoresis hence they are termed pre-B lipoproteins
Very low-density lipoproteins (VLDL)
Is synthesized in the liver
This fraction is markedly elevated in type IV hyperlipoproteinemia
VLDL
Contain mainly cholesterol in contrast to the content of chylomicrons and VLDL
LDL
They migrate together with B-globulins
They are termed B-lipoproteins
LDL
The fraction is markedly elevated in Type II Hyperlipoproteinemia and is associated with a high incidence of atherosclerosis
LDL
Contain mainly protein and phospholipid
They contain significant amounts of cholesterol but have little triglyceride
High density lipoproteins HDL
The high protein, low triglyceride content makes them very dense
They are termed alpha-Lipoproteins
High density lipoprotein HDL
3 main classes of lipids are found in biological membranes:
Phospholipid
Glycolipid
Cholesterol
Lipid bilayer is
amphipathic
“Water-loving” polar head group
Hydrophilic
“Water-hating” non-polar tails
Hydrophobic
Inherited disorder characterized by significant reduced levels of high-density lipoproteins in the blood
Orange tonsils Hepatomegaly Neuropathy (mononeuritis simplex) Low or absent HDL-C Premature CV disease
Tangiers disease
Familial Alpha Lipoprotein Deficiency
Tangiers disease results from a mutation of a transmembrane protein that transports phospholipid & cholesterol out of the liver to generate HDL
ABCA1
Functions of lipid
As energy source 9kcal/gram
Protein sparer
Facilitates absorption of fat soluble vitamins
The only absolute essential fatty acid (EFA)
Precursor of arachidonic acid
Linoleic acid
FA that reduces risk of heart disease
Omega 3
FA that potentially significantly improves autism
Docosahexanoic acid
Omega 3
Extramitochondrial lipogenesis
Sources of NADPH
HMP shunt
Malic enzyme reaction (Malate -> Pyruvate)
Rate limiting step of extramitochondrial lipogenesis
by enzyme
Conversion of acetyl coA to malonyl coa
acetyl coa carboxylase
18 C
soaps, shampoos, detergents, shaving creams
Stearic acid
16 C
Palmitic acid
Body can synthesize needed fat except
Linoleic
Alpha linolenic
Alpha linolenic acid
Omega 3 FA
Linoleic acid
Omega 6 FA
Omega 3 fatty acids
Alpha linolenic acid (ALA) Eicosapentanoic acid (EPA) Docohexanenoic acid (DHA)
Nerve problem treatment
ALA
Omega 6 Fatty acid
Linoleic acid
Omega 3
Alpha Linolenic Acid (ALA)
then
Eicosapentaenoic acid (EPA) Docosahexaenoic acid (DHA)
Intestinal mucosal cells secrete nascent TG-rich
chylomicrons
Liver secretes nascent TG-rich
VLDL
Neutral lipid core (triacylglycerol + cholesterol ester) surrounded by a shell of apolipoproteins, phospholipids, nonesterified cholesterol
Soluble in aqueous solution
Lipoprotein
Lipoprotein with lowest density
Largest in size
Most lipid
Smallest percentage of protein
Chylomicron
Chylomicron inherent apolipoprotein
ApoB-48
Nascent VLDL (liver) inherent apolipoprotein
Apo-B100
Transferred from HDL to nascent CM and VLDL
ApoCII
ApoE
Activated by apoCII and degrades triacylglycerol in chylomicrons and VLDL
Found in capillaries of tissue adipose, cardiac and skeletal muscle
Lipoprotein lipase
Lipoprotein lipase degrades (hydrolyzes) TAG of chylomicrons and VLDL into
Free fatty acid
Glycerol
Monoacylglycerol
and be sent back to Liver
Most electrophoretic mobile lipoprotein
Chylomicron
Least electrophoretically mobile lipoprotein
HDL
Deficiency of lipoprotein lipase or apo-CII
Dramatic accumulation of triacylglycerol rich lipoproteins in plasma
Type I Hyperlipidemia
Familial hyperchylomicronemia
C apolipoproteins after activation of lipoprotein lipase are returned to
HDL
The cholesterol released from chylomicron regulates the
Rate of de novo synthesis of cholesterol
Inc cholesterol from chylomicron decreases HMG Coa reductase
allosterically inhibits the enzyme
Carries lipid produced in the liver to peripheral tissues
TAG in this lipoprotein is also degraded by lipoprotein lipase
Contains apo B100 and A-I
VLDL
Once degraded, apo C-II and apo E go back to HDL and in exchange,
cholesteryl ester from HDL are transferred to VLDL with concomittant TAG and phospholipid transfer from VLDL to HDL
Transfer of cholesteryl esters from HDL to VLDL in exchange for triacylglycerol or phospholipid is accomplished by
cholesteryl ester transfer proteins
In the plasma, after exchange of cholesteryl ester VLDL is transformed into
LDL
Intermediate sized particle observed during transition from VLDL to LDL
Intermediate density lipoprotein
Retain apoB100 but lose apolipoproteins for HDL
Contain less TAG than VLDL
Higher concentration of cholesterol and cholesteryl ester
Primary function is to provide cholesterol to peripheral tissues by deposition
LDL
Deficiency of functional LDL receptors on cell surfaces causing significant elevation of LDL and cholesterol
BUT NORMAL TAG
Type II hyperlipidemia
Familial hyperbetalipoproteinemia
accelerates atherosclerosis
Degrades TAG containing SHORT FATTY ACIDS
Secreted by stomach on the stomach
Gastric lipase
Degrades TAG (removes fatty acid from carbon 1, 3 leaving monoacylglycerol)
Requires pancreatic colipase for stabilization
Secreted by pancreas and sent to intestines
Pancreatic lipase
Degrades TAG circulating in chylomicrons of VLDL
releasing non-esterified fatty acids and glycerol
Can be released by plasma into plasma by Heparin activated apoprotein C-II
Secreted by extrahepatic tissues on the surface of epithelial cells lining capillaries
Lipoprotein lipase
Degradation of stored triacylglycerol
Activated by cAMP dependent protein kinase
Secreted by adipocytes in the adipocyte cytosol
Hormone sensitive lipase
Removes fatty acid from lipids taken into cells during phagocytosis
Acid pH optimum
Secreted by most tissues acts on lysosomes
Acid lipase
Functions of HDL
synthesized in liver and released by exocytosis
circulating reservoir of apoC-II to activate lipoprotein lipase
removing free unesterified cholesterol from extrahepatic tissues and esterifying it using phosphatidylcholine:cholesterol acyl transferase (PCAT/LecithinCAT) activated by apoA-I (inc in modest alcohol intake)
transfers cholesteryl ester to VLDL and LDL in exchange for TAG
carries cholesteryl ester to liver where HDL is degraded and cholesterol released
Decreased concentration of plasma cholesteryl ester due to deficiency in
PCAT
phosphatidylcholine production
Lipoprotein is identical to LDL except it has additional apolipoprotein molecule
this slows down breakdown of blood clots that trigger heart attacks due to similarity in amino acids 80% with plasminogen
apolipoprotein a