biochem
poorva
PHAR150GBiochemistryDay9.pptxPHAR150G
Lipids 1
Vicky Mody, PhD
Associate Professor of Pharmaceutical Sciences
Office , Rm 3034
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Define the terms lipids, fatty acid and classify biological lipids
Explain structure & nomenclature of naturally occurring fatty acids
Explain structure, nomenclature & functional importance of storage lipids namely triacylglycerols and waxes
Explain structure, nomenclature & functional importance of membrane lipids
Explain function of lipids as biological signal molecules
Explain effects of trans-fatty acids on metabolism
Learning objectives for Lipids 1-2
Lipids
“Water insoluble biomolecules that are highly soluble in organic solvents”
i.e. are mostly nonpolar
Defining characteristic: hydrophobicity
Another definition: “are fatty acids and their derivatives, and substances related biosynthetically or functionally to these compounds”
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Biological Roles of Lipids
Fuel molecules/Energy stores (triacylglycerols)
Components of membranes
(e.g. phospholipids, cholesterol)
Signal molecules (e.g. steroid hormones, prostaglandins)
Solubilize/absorbing fats (bile salts)
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Different of Lipids of our Interest
Fatty Acids
Acylglycerol (Triacylglycerides, monoacylglycerides)
Phosphoacylglycerols (Phospholipids)
Sphingolipids
Steroids
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Cholesterol
Fatty Acids
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8
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What do we know about Fats
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10
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What are Fatty Acids:
Structure:
Acidic carboxylate group
Lipophilic (fatty) alkyl chain
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Different Types of Fatty Acids:
Saturated
Fatty Acids
Unsaturated
Fatty Acids
Polyunsaturated
Fatty Acids
Polyunsaturated
Fatty Acids
18:1, 9
18:3, 9, 12, 15
20:4, 5, 8, 11, 14
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http://www.omegadefend.com/3/about-fatty-acids.html
Different Types of Fats
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Why does it matter what kind of Fat it is
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Why does it Matter:
18:1, 9
18:3, 9, 12, 15
20:4, 5, 8, 11, 14
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Why does it Matter:
18:1, 9
18:3, 9, 12, 15
20:4, 5, 8, 11, 14
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Effect of Saturation on Physical Properties
18:1, 9
18:3, 9, 12, 15
20:4, 5, 8, 11, 14
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Effect of Saturation on Physical Properties
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The melting point of a fatty acid increases with chain length and decreases with the degree of unsaturation.
Thus, fatty acids with many double bonds, such as those in vegetable oils, are liquid at room temperature;
Saturated fatty acids, such as those in butterfat, are solids.
Lipids with lower melting points are more fluid at body temperature and contribute to the fluidity of our cellular membranes.
Fatty Acids
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Saturated and Unsaturated Fatty Acids
(a PUFA)
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Saturated from Unsaturated Fats Cis vs Trans
Most naturally occurring unsaturated FA are cis.
Traces of Trans can be found in animal milk.
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Fatty acids are usually straight aliphatic chains with a carboxyl group at one end.
Most fatty acids in the human have an even number of carbon atoms, usually between 12 and 24.
Saturated fatty acids have single bonds between the carbons in the chain, and unsaturated fatty acids contain one or more double bonds.
Fatty Acids
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The most common saturated fatty acids present in the cell are palmitic acid (C16) and stearic acid (C18).
Palmitoleic acid (16:1) (Not Palmitic acid) and Oleic acid (18:1) are most important monounsaturated fatty acids (MUFA) in human cells.
Fatty Acids
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Naming Fatty Acid
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Fatty acids are often called by the Latin word for the number of carbons, such as;
Octanoic acid (8 carbons).
Decanoic acid (10 carbons).
Dodecanoic acid (12 carbons)
Tetradecanoic acid (14 carbons)
Hexadecanoic acid (16 carbons)
Octadecanoic acid (18 carbons)
Eicosanoate (20 carbons)
Doeicosanoate (22 carbons)
Fatty Acids
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C18:0 octadecane → octadecanoic acid
C18:1 octadecene → octadecenoic acid
C18:2 octadecadiene → octadecadienoic acid
Nomenclature of Fatty Acids based on Parent Compound
NOTICE EVEN
NUMBERED CARBON
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subliminal message:
Read the Textbook!!!
Nomenclature of Fatty Acids
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Monounsaturated fatty acids contain one double bond, and polyunsaturated fatty acids contain two or more double bonds.
The position of a double bond is designated by the number of the carbon in the double bond that is closest to the carboxyl group.
Fatty Acids
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IUPAC nomenclature: Carboxyl carbon is C-1
Common nomenclature: α,β,γ,δ,ε etc. from carbon next to acidic group
Carbon farthest from carboxyl is ω
Nomenclature of Fatty Acids
18:1, 9
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Oleic acid, which contains 18 carbons and a double bond between positions 9 and 10, can also be designated as 18:1, 9.
The number 18 denotes the number of carbon atoms, 1 (one) denotes the number of double bonds, and 9 denotes the position of the double bond between the 9th and 10th carbon atoms.
Oleic acid can also be designated 18:1(9)___________
Nomenclature of Fatty Acids
18:1, 9
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18:1, 9
18:3, 9, 12, 15
20:4, 5, 8, 11, 14
Nomenclature of Fatty Acids
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Double bond position can also be denoted by (e.g. 9 means a double bond between carbons 9 and 10)
Nomenclature of Fatty Acids
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Hexadecanoic acid can also be labeled as
4 hexadecenoic acid
w-4 hexadecenoic acid
a-hexadecanoic acid
-3 hexadecenoic acid
-13 hexadecenoic acid
HINT: 16 carbon chain fatty acid is called hexadecanoic acid
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4 decenoic
-8 decenoic acid
3 decenoic acid
7 decenoic acid
-3 decenoic acid
-4 decenoic acid
Decenoic acid can also be labeled as
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4 decenoic
-8 decenoic acid
-7 decenoic acid
-3 decenoic acid
-4 decenoic acid
Decenoic acid can also be labeled as?
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Lets Review
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Saturated Fats
High in animal fats (butter, lard) & palm, cottonseed, coconut
CV effect from saturated fats widely believed harmful
May negatively affect cholesterol levels
WHO, AHA, CDC recommend decrease saturated fat intake
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Saturated Fats
The “Inuit paradox”
Previously almost no heart disease
But huge proportion of diet consisted of seal, whale, walrus blubber
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Polyunsaturated Fats
In nuts, cheese, fish, greens, etc.
e.g. Docosahexaenoic acid (DHA)
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Fat Content In selected Oils/Food
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http://www.benbest.com/health/essfat.html
Can be converted to EPA and DHA
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Importance of Alpha-Linoleic acid (ALA)
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Linolenic and Alpha-Linolenic acid
-Linolenic acid (ALA)
EPA
Only ALA can synthesize EPA and DHA
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Possible therapeutic benefits of EPA/DHA or fish oil
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Linolenic acid vs Alpha Linolenic Acid
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Alternative to Linolenic acid?
Monsanto’s low linolenic acid soybean
3% linolenic (vs. 8% )
Currently worth 50-60% more/bushel
Allows processors to “meet food companies' demand for no or low trans fat oils”
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Sources of Fatty Acids, Omega-3,and Omega-6
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Source of Fatty acids
Most of the “nonessential” fatty acids come from diet but body can also biosynthesize them.
Exceptions:
linoleic [18:2(9,12)]; an omega-6 fatty acid
-linolenic [18:3(9,12,15)]; an omega-3 fatty acid
these are “essential fatty acids”
-Linolenic acid
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Ratio of Omega-3 and 6
w-3 and w-6 FAs
ratio may be important for health:
Junk diet is usually too high w-6 (e.g. linolenic)/not enough w-3
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Essential Fatty Acids
Historically in west: probably close to 2:1 ratio of omega-6:omega-3
Last 30 years: substantial increase in linoleic (omega-6) due to increased vegetable oil consumption
Ratio now closer to 20:1
and historical change in diet
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Importance of Omega-3 and Omega-6 Fatty Acids
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(LT4)
(LT5)
Importance of Omega-3 and Omega-6
Very low conc
Not clinically imp
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Both are transformed into eicosanoid signaling molecules. NOTE eicosanoids have 20 carbon atoms
Eicosanoids mediate inflammation (both pro and anti) & immunity.
Necessary to stimulate development of skin and other tissues, & brain function.
Eicosanoids from omega-6 more powerful than those from omega-3.
Use of Essential Fatty Acids
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sources in diet
very low conversion rate
very low conversion rate
Transformations of Essential Fatty Acids
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Omega-3 fatty acids
Eicosapentaenoic acid (EPA) 20:5 (5,8,11,14,17)
Docosahexaenoic acid (DHA) 22:6 (4,7,10,13,16,19)
ALA converted to EPA, DHA
but rate limited, so diet should include all
“Conditionally essential
fatty acids”
alpha linolenic (ALA) : essential
DHA
EPA
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Omega 3 fatty acids
ALA: mostly in plants
nuts, flaxseed, canola, wheat germ
DHA, EPA: mostly in animals
breast milk, and fish (such as salmon, sardines, herring, halibut, tuna)
Sources in diet
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Omega 3 fatty acids
In fish oil: common dietary supplement
DHA and EPA
FDA allows labeling "The scientific evidence about whether omega-3 fatty acids may reduce the risk of coronary heart disease is suggestive, but not conclusive."
American Heart Association (AHA) recommends including fish in diet for all individuals, and fish oil supplements in those with a history of cardiovascular disease
“the inuit paradox”
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What other types of fats are common in our Food
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http://www.benbest.com/health/essfat.html
Can be converted to EPA and DHA
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Oleic acid (18:1) is one of the most important monounsaturated fatty acid (MUFA) in human cells. It is present in membrane phospholipids, triglycerides, and cholesterol esters.
The consumption of MUFAs is important to maintain low levels of LDL in the blood and is also likely to be associated with the potential for elevated HDL.
Oleic acid
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Oleic acid is present in Olive oil as triglyceride.
Free oleic acid levels in food grade olive oil are mandated to be less than 2% as more than this makes the oil inedible.
Extra virgin olive oils will have less than 0.8% free oleic acid.
Other vegetable and nut oils also contain high levels of oleic acid in their triglycerides form.
Oleic acid
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Most Oils are Present as Triglycerides as Compared to Simple Fatty Acid
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What are Trans Fats
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Trans Fatty Acids
Most naturally occurring unsaturated FA are cis.
Trans can be found in animal milk.
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Trans Fatty Acids
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Which is more Reactive cis or trans
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Which is More reactive- Cis or Trans?
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Synthesis of Saturated Fatty Acids
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The parital hydrogenation is a reduction process that is used to synthesize saturated fats.
Oleic acid
stearic
Pd/H2
Hydrogenation of Unsaturated Fatty acids
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Michel Eugène Chevreul
Margaric acid
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Synthesis of Trans Fat during Saturation of Fatty Acids
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Most naturally occurring unsaturated FA are cis
Trans can also be formed on partial hydrogenation
oleic
stearic
Pd/H2
+
cis
trans
elaidic
Trans fat in Partially Hydrogenated Soybean Oil
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So no Trans Fat in Partially Hydrogenated Food Products?
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Crisco “0 g. trans fat per serving”
~30% trans fat prior to reformulation
margarine ~15%
butterfat up to 4%
FDA: foods w/ < 0.5 g. trans fat/serving can have the above statement
FDA: ave. American gets 5.8 g trans fat/day
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Trans-fats
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Trans-fats in American Diet
Most trans fat in American diet is from partial hydrogenation
Some is natural e.g. vaccenic acid (trace) found in dairy prod. & human milk
vaccenic acid (18:1 trans-11)
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Health Implications of Trans-fats
Consumption increases heart disease
increases “bad” cholesterol (LDL)
decreases “good” cholesterol (HDL)
Possibly 30,000-100,000 deaths/year due to trans fat consumption
vaccenic acid (18:1 trans-11)
"Trans fatty acids and cardiovascular disease". N. Engl. J. Med. 2006, 354 (15): 1601–13
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Lipids, fatty acid and different types of biological lipids
Structure & nomenclature of naturally occurring fatty acids
Structure, nomenclature & functional importance of storage lipids namely triacylglycerols and waxes
Structure, nomenclature & functional importance of membrane lipids
Function of lipids as biological signal molecules
Effects of trans-fatty acids on metabolism
Summary
OH
O
HO
O
stearicacid(18:0)
asaturatedfattyacid
oleicacid(18:1)
amonounsaturatedfattyacid
HO
O
HO
O
apolyunsaturatedfattyacid
(18:2)
HO
2
C
HO
2
C
