Lipid Structure and Function Flashcards
What three important roles do lipids serve?
Energy storage
Cell membranes
Signaling
What is the common and defining feature of lipids?
Hydrophobicity
What are most lipids derived from?
Fatty acids
What are fatty acids?
Consist of a carboxylic acid and a hydrocarbon tail (4 - 36 carbons)
Can covalently bond to proteins to (lipid) tether proteins to biological membranes
What are the most abundant natural fatty acids?
unbranched
contain 12-20 carbons
even-numbered
- acetyl CoA (2 carbons)
What are saturated fatty acids?
Contain fully reduced methylene groups
- no double bonds
- all single bonds
What are unsaturated fatty acids?
Contain at least 1 double bond
Monounsaturated
- 1 double bond
OR
Polyunsaturated
- more than 1 double bond
What affects the structure of fatty acids?
The degree of saturation and the configuration
What is the structure of saturated fatty acids?
Free rotation about every C-C bond and are largely linear
What is the structure of unsaturated fatty acids?
Rotation is restricted about the C=C bond
In the structure of unsaturated fatty acids, the cis configuration of the C=C bond introduces what?
Cis of C=C bond introduces a bend (kink) in the fatty acid
Whereas a trans C=C bond is more linear
Describe standard fatty acid nomenclature.
Assigns number 1 to the carboxyl carbon (C-1), and a (alpha) or number 2 to the carbon next to it
Each line segment of the zigzag represents a single bond between adjacent carbons
The position of any double bond(s) is indicated by △ followed by a superscript number indicating the lower-numbered carbon in the double bond
What are PUFAs?
Alternative Nomenclature for Polyunsaturated Fatty Acids - Omega Fatty acids
Describe Alternative Nomenclature for Polyunsaturated Fatty Acids.
Carbons are numbered in the opposite direction, assigning number 1 to the methyl carbon (also designated ω) at the other end of the chain
The positions of the double bonds are indicted relative to the ω carbon
PUFAs with a double bond between C3 and C4 are called Omega-3 fatty acids and those with a double bond between C6 and C7 Omega-6 fatty acids
Describe structure of an omega-3 fatty acid.
First relation with omega carbon (where the first double bond is from the omega carbon 1)
What configuration are the majority of fatty acids?
Cis configuration
Which 2 Omega fatty acids are needed in our diet?
a-linolenic acid, Omega-3 fatty acids
Linoleic acid, Omega-6 fatty acids
(opposite sides of double bond placement)
We have enzymes needed to convert linoleic acid into arachidonic acid, and a-linolenic acid to EPA and DHA
What does unsaturation cause in lipids?
Causes a physical change
The length and degree of saturation of the fatty acid affects the melting point of lipids
How does length of the fatty acid affect the melting point of lipids?
Increases as the chain length increases
Decreases as the number of bonds increases
Summary: The more kinks, the less tightly packed (not as many favorable reactions) which is why melting point is lower
- i.e. butter in fridge (oily when left out)
How does degree of saturation of the fatty acid affect the melting point of lipids?
Saturated fatty acids pack in a fairly orderly way
- extensive favorable interactions
Unsaturated cis fatty acid pack less orderly due to the kink
- less-extensive favorable interactions
- it takes less thermal energy to disrupt disordered packing of unsaturated fatty acids
Do saturated or unsaturated fatty acids take less thermal energy to disrupt disordered packing of them?
Unsaturated fatty acids
What are the other names for fats?
Triacylglycerides (TG)
Tricacylglycerols (TAG)
Fats
What are the main function for triacylglycerols and what do they contain?
energy storage in animals
contains 3 fatty acids esterified to a glycerol
What does 3 unsaturated fatty acids usually make?
oil
Compare the complete oxidation of glycogen and TAG.
Glycogen results in ~6kJ/g
TAG results in ~38kJ/g
What are TAGs derived from?
Dietary sources
Liver biosynthesis
Adipocytes
How are dietary triacylglycerols transported to the circulatory system?
By chlomicrons
How are triacylglycerols synthesized in the liver exported and packaged?
exported in lipoproteins
packaged in VLDL Particles
Triacylglycerols stored in adipose tissue are hydrolyzed and released as what? How are they transported?
hydrolyzed and released as free fatty acids and glycerols by hormone signaling
transported by albumin, a carrier protein.
What are essentially insoluble in water in this section?
Triacylglycerols and Cholesteryl esters
Yet must be moved from tissue of origin to the tissues where they will be stored or consumed
To facilitate their transport, triacylglycerols and cholesteryl esters are carried in the blood plasma as ____.
Lipoprotein particles (entire particles)
What are apolipoproteins?
Specific carrier proteins that combine with lipids to form several class of lipoprotein particles
Function to promote lipoprotein
particle formation in endomembrane systems of cells and also serve as molecular tags
for lipoprotein metabolism in the body
“Apolipoproteins” refers to the protein part of the lipoprotein particle
What are lipoprotein particles?
Spherical complexes with hydrophobic lipids in the core and hydrophilic amino acid side chains at the surface
What are the four major classes of lipoprotein particles? (include densities as well)
Chylomicrons (50-200 nm)
- largest and least dense
Very low-density lipoproteins (VLDL)
- 28-70 nm
Low-density lipoproteins (LDL)
- 20-25 nm
- bad cholesterol
High-density lipoproteins (HDL)
- 8-11 nm
- smallest, most dense
- good cholesterol
What is the specific function of chylomicrons?
Transport TAG and cholesterol from intestinal epithelia to tissues
What is the specific function of VLDL?
Transport excess TAG and cholesterol from liver to adipose tissue
What is the specific function of LDL?
Transport cholesterol to non-hepatic tissues
What is the specific function of HDL?
Transport cholesterol from blood to liver (for excretion) and steroidogenic tissues (for steroid hormone synthesis)
Dietary TAGs are transported by ____.
Chylomicrons
What is the largest of all lipoprotein particles?
Chylomicrons
What kind of membrane does chylomicrons consist of?
Monolayer of phospholipid membrane containing free cholesterol
The phospholipid membrane is embedded with up to 6 different apolipoproteins
What does the interior of the chylomicron particle contain?
Large amounts of TAGs and cholesterol esters, which are destined for delivery to peripheral tissues
Cholesterol has to be hydrophobic so it is esterified
What enzymes metabolize dietary TAGs in the intestine before being exported to the circulatory system as components of Chylomicrons?
- Bile acid which will break down the TAGs
- dietary TAGs emulsified by bile acids - Lipase cleavage which will break the bond of glycerol and fatty acid
- Fatty acids resynthesized into triacylglycerols
- Triacylglycerols packed into chylomicrons
- Chylomicron export to lymphatic system
- Enters circulatory system through the left subclavian vein
What is ApoC-II?
On the surface of chylomicrons
Binds to and activates lipoprotein lipase on endothelial cells, leading to the release of fatty acids and glycerol
What does lipoprotein lipase do?
Cleaves acyl ester bonds and releases fatty acids and glycerols
What is albumin?
Carrier protein for free fatty acids in blood plasma
- binds to fatty acids
Most abundant plasma protein
Protects cell membranes from the detergent effect of free fatty acids
What are the fatty acids synthesized in the liver from and used for?
From acetyl-CoA in the cytosol
Used to generate TAGs in the endomembrane system before being packaged into VLDL particles
THIS IS IN THE ER
Where do VLDL particles that are secreted transported to?
Peripheral tissues
What stores TAGs in lipid droplets?
Adipocytes
What are lipid droplets?
Storage sites for newly formed TAGs in adipocytes
What is liposuction?
Surgical procedure that removes adipocytes from fat deposits in the body
What are lipid droplets surrounded by?
Phospholipid monolayer containing large amounts of the protein Perilipin which protects them from the lipases
Once perilipin is phosphorylated, lipases can then attach
What kind of hormonal signaling in adipocytes stimulate release of free fatty acids (FFAs) from TAGs stored in lipid droplets?
Gluacgon signaling
How are free fatty acids released by lipase cleavage?
Sequestered by fatty acid binding protein 4 and then exported to the circulatory system
Where they are transported to peripheral tissues by the carrier protein albumin
What are cell membranes made of?
Lipids and proteins
What are the 3 major types of membrane lipids?
Glycerophospholipids (major component)
Sphingolipids
Cholesterol
What are glycerophospholipids?
Most abundant membrane lipids
Addition of a polar head group to phosphatidate
2 fatty acids here with a phosphate group at C3
What is the substrate for glycerophospholipid synthesis?
Phosphatidate
What is a phosphatidate?
2 FAs and a phosphate group attached to a glycerol
What are examples of glycerophospholipids? (just be able to identify them)
Phosphatidyl-serine
Phosphatidyl-ethanolamine
Phosphatidyl-choline
Phosphatidyl-inositol
What are sphingolipids?
Addition of a polar head group to sphingosine
Derived from Ceramide (Sphingosine and one fatty acid)
No glycerol compared to glycerophospholipid
What is spingosine?
Synthesized by linking serine to the carboxyl group of palmitate
What are the two most common types of sphingolipids?
Sphingophospholipids
Sphingoglycolipids
How much does cholesterol constitute for lipids in the plasma membrane?
25-40%
What affects the fluidity of the membrane?
Cholesterol
Cholesterol is a metabolic precursor to?
Steroid hormone for cell signaling (Progesterone)
Bile acid biosynthesis for digestion (Glycocholate)
What are two sources of cholesterol?
diet
biosynthesis
What is the structure of cholesterol?
4 rings
C27 tetracyclic molecule of a planar ring system with a polar -OH group on one end and a hydrophobic alkyl side chain on the other end
How are glycerophospholipids and sphingolipids differentially distributed in the membrane?
two monolayers
Is the overall cholesterol content of the inner and outer monolayers of the erythrocyte plasma membrane similar?
Yes they are similar
What are lipid rafts?
Discrete membrane regions that contain high concentrations of cholesterol and an aggregation of transmembrane receptor proteins and glycoproteins involved in cell signaling
Is the membrane thicker or thinner in the region of the lipid raft?
Thicker because transmembrane glycoproteins are thicker
What does the hydrophobic property of lipids contribute to in cell signaling?
Function as high-affinity ligands that bind to hydrophobic properties in receptor proteins
What is arachidonate?
precursor for immune regulatory molecules called “Eicosanoids”
What is a precursor to vitamin D (cholecalciferol)?
7-Dehydrocholesterol
What are the functions of steroid hormones?
Endocrine signaling
Half life of hours
What are eicosanoids?
a group of signaling molecules derived from C20 PUFAs such as Arachidonate
How is arachidonate used as a response to GPCR signaling?
Arachidonate is released from the membrane by phospholipases and further modified
What is paracrine’s half-lives?
Half-lives of only a few minutes
What are the cyclooxygenase enzymes?
COX-1 and COX-2 and are differentially inhibited by aspirin and ibuprofen.
COX-2 is also inhibinited by rofecoxib and celecoxib
What are non-steroidal anti-inflammatory drugs (NSAIDs)?
Nonselective COX-1/COX-2 inhibitors such as aspirin and ibuprofen are small molecules that bind to the active site of both COX-1 and COX-2
What is the function of COX-1?
protects against stomach ulcers
but COX-1 inhibition can lead to the development of ulcers
What is the function of COX-2?
mediates joint inflammation
but COX-2 inhibition reduces join inflammation
What are selective COX-2 inhibitors?
Rofecoxib (Vioxx) and Celecoxib (Celebrex)
What happens when Selective COX-2 inhibitors inhibit COX-2?
It won’t fit COX-1, making it not inhibited and no stomach ulcers
It will inhibit COX-2 and reduce inflammation, pain and fever
BUT creates a new problem where the Selective COX-2 inhibitors do not fit prostacyclin synthase perfectly and only partially inhibits it resulting in increased platelet aggregation, formation of blood clots
