Triacylglycerol, Phospholipids Flashcards
How can lipids be defined?
What are 2 common properties?
Heterogenous group of biological compounds, including fats, oils, steroids, waxes, that are relatvely insoluble in water
- Relatively insoluble to water (hydrocarbon chains)
- Soluble in nonpolar solvents (ex: ether and chloroform can be used for lipid isolation)
What are some functions of lipids?
- ENERGY STORAGE
- Important dietary components because of their high energy
- Structural components of bio membranes
- Serve as thermal insulators in subcutaneous tissues and around certain organs
- Signaling molecules (PI, Leukotrienes)
- Hormones precursors (ex: steroids)
What configurations do lipid take in aqueous envrionments?
Fatty acids form micelles → hydrophobic core surrounded by the polar heads
(fatty acids have only 1 tail so easy to compact)
Phsopholipids form Bilayers or Vesicles (loop of bilayer)
*2 hydrocarbon chains
What is special about acetic acid?
It is a lipid, but 100% soluble in H2O because it has a very very short hydrocarbon chains (1C)
What is the structure of a basic fatty acid?
Carboxylic acid (COOH) polar head + 1 long hydrocarbon (CH) tail
Saturated → only single bonds, all C have 2xH atoms
Unsaturated → 1 or more double bonds
How do we name a lipid composed of 2 phospholipids bound together?
Cardiolipin
Where in cells are lipids found?
- Plasma membrane (phospholipids are “stored there”)
- Mitochondrion (for beta-oxidation → very transient)
- Cytosol (Fatty acid biosynthesis → very transient)
- ER (phospholipid and neutral lipid biosynthesis → transient)
- Lipid droplets (lipolysis → stable storage, in micelle or vesicle conformations)
What is Atherosclerosis?
the buildup of fats, cholesterol and other substances in and on the artery walls → forms plaque which narrows the artery
Can cause a stroke or heart attack due to lack of O2 to the muscles or the brain
What are purified lipids?
Butter, Oil
Composed of 3 acyl chaines + glycerol backbone → Triacylglycerol
Neutral lipids → very insoluble in water
Saturated acyl chains → solid at room Temp
Unsaturated acyl chains → liquid at room Temp
What are the different cellular lipids?
Lipid droplets → Triacylglycerol, Cholerteryl esters → Neutral lipids
Membrane lipids → Phospholipids, Spingolipids, Glycolipids, Cholesterol → Amphipatic
What si the role of i-FABP?
Intestinal Fatty acid binding protein
- Carries FA inside enterocytes (and from one compartment to another inside the cell)
How do lipids pass from the small intenstin lumen → blood?
- Mucosa of the small intestin allows absorption of Fatty Acids, MAG, sterols
- ER of microvilli epithelial cells → Chylomicron assembly:
- Triacylglycerol
- Cholestrol
- ApoB48 - Chylomicron secretion from epithelial cells to circulation
- Transported in the blood via lipoproteins (forming chylomicrons)
- Stroed in cells in lipid droplets (triglycerides) or used to generate phospholipids
How are lipids absorped from mucosa to epithelial cells?
In the lumen:
- Pancreatic Lipase → hydrolyzes 2-Monoglyceride + 2 free fatty acids → uptaken by brush border intestinal cells
- Bile salts → help with micelle formation by forming a hydrophilic surface (for free fatty acids)
*Bile salts are produced by the liver
pH protonates Fatty acid chains → internalized by vesicles
Where in the cell are fatty acids the most present?
Mitochondrion → beta-oxidation
Cytosol → Fatty acid biosynthesis
*Very transient
How does the melting point fluctate when the number of carbons change in the hydrocarbon chain?
More Carbons → melting point goes up
What happens to the melting point when the number of unsaturations goes up?
More unsaturation → decrease in melting point
From highest → lowest melting point:
Saturated → trans-unsaturated → cis-unsaturated
What abreviation can represent the structure of different fatty acids?
Saturated: 10:0 → 10 carbons, 0 double bonds
Unsaturated:
Delta) 18:2c∆9,12 → 18 carbons, 2 double bonds a positions 9 and 12 from the COOH group
Omega) 18:2(w6,9) → 18 carbons, 2 same double bonds, but start counting at the carbon the most distant from carboxyl group
What are Cis vs Trans fatty acids?
Different isomers of unsaturated FA
Cis → radicals are on the same side of double bond → bent molecule, disturbs solid phase
Trans → radicals on opposit sides of double bond → straight molecule
- Higher melting points because pack more regularly → more solid at room temps → increases risk of cardiovascular diseases
- Trans fats are produced by partial hydrogenation of vegetable oils in the food industry → converts cis double bonds to trans configuration
What are the characteristics of branched-chain fatty acids?
Uncommon in humans, only have 2:
- Pristanic acid
- Phytanic acid
Present in bacteria and some ruminants (ex: dairy products)
Undergo a-oxidation (peroxisome) instead of b-oxidation (in mitochondria)
What are Isoprenoids?
Not a branched-chain Fatty acid, different type of molecule similar to fatty acid with some branching
Ex: GPP
What is the structure and the characteristics of triglycerides?
3 acyl chains + 1 glycerol
- 100% hydrophobic
- Excellent way to package and transport fatty acids
- Present in many foods: Olive oil, Butter, Beef fat
- Stored in vesicles
*Glycerol = C bound to 3 Oxygens from COOH groups of fatty acids
What are the characteristics and the structures of the 2 main membrane lipids?
Membrane lipids are amphipathic: Polar head group + hydrophobic tail
- Phospholipids → 2 hydrophobic tails, 1 saturated, 1 cis-unsaturated
- Glycerol/Spinegosine + acyl chains - Cholesterol → 1xSaturated hydrophobic tail + rigid steroid ring structure + polar head group
What are the different pathways for triglyceride breakdown (lipolysis)?
(Where)
- Pancreatic Lipase (GI-tract)
- Lipoprotein Lipase (Blood Vessels)
- Lipid droplets (adipose & liver)
What is the level of hydrophobicity of Triacylglycerol (aka Triglycerides) ?
100% hydrophobic
Free fatty acids alone are a bit more hydrophilic because they have the COO- terminal
What are the ways of transport of triglyceride in the blood?
Chylomicrons → Dietary triglycerides (exogenous pathway) → from small intestine
VLDL → Endogenous triglycerides → from the liver
Where in the cells are triacylglycerol (triglycerides) located?
Stored lipid droplets
Explain the exogenous pathway of lipolysis.
- Ingested in stomach/Gallbladder → emulsified by bile salts
- Pancreatic lipase hydrolyzes them - Transported (Chylomicrons)
- Stored → as triaceylglycerols
- Mobilized to generate energy → sent to the muscle, heart, liver → CO2 + H2O + ATP
Explain the endogenous pathway of Lipolysis.
- Synthesized in the liver
- Transported (VLDL)
- Stored → adipose cells
- Free fatty acids are transported bound to serum albumin - Mobilized to generate energy
How does Lipolysis in the GI-tract occur? How is it regulated?
In fed state (very quick/as we are eating):
Triglycerides → {Pancreatic Lipase} → Monoglycerides + free fatty acids → cross the membrane of intestinal epithelial cells → reassembly
Regulated by substrate availability (Triglycerides)
How can charged fatty acids cross the non-polar membrane bilayer?
*They are a more bit hydrophilic as free fatty acids than in triacylglycerol form because of COO- terminal
- Specific transporter
Possible mechanism: acidification of pinocytic vesicle neutralizes the charged FA
1. Extracellular fluid → pH~7.0 → FA = charged (COO-)
2. Internalized pinocytic vesicle → pH~5 → FA = neutral (protonated)
3. Diffusion across membrane of the intracellular vesicle → cytoplasm
4. Cytoplasm → pH~7 → FA = charged
How does Lipoprotein Lipase occur in the blood vessels?
How is it regulated?
Lipoprotein Lipase is located at the surface of muscle/adipose cells
→ Occurs in fed state when chylomicrons transport TG to cells through circulation:
Triglycerides → LPL → Monoglycerides + free fatty acids
Regulation through substrate availability
What are the differences in lipid droplets between adipose cells and liver cells?
Adiocytes → large lipid droplet fills the cell, nucleus is squeezed to the side
Liver → much smaller lipid droplets:
- Serve as transient buffer reservoir of esterified fatty acids (TG) and esterifed cholesterol
- Central nucleus
What reaction is associated with lipolysis in lipid droplets?
When fasting or during exercise, chop the FA one-by-one:
Triacylglycerol → {ATGL} → Diaceylglycerol → {HSL} → Monoacylglycerol → {MGL} → Glycerol
ATGL = adipose triglyceride lipase
HSL = hormone-sensitive lipase
MAG = monoacylglycerol
How is Lipolysis in lipid droplets hormonally regulated ?
In adipocytes:
Epinephrine → binds Gas-coupled receptor → Gas dissociated → activates adenyl cyclase → increase in [cAMP] → active PKA → phosphorylation HSL & perilipin
Phosphorylated perilipin → change inconformation → opening of lipid droplet → allows entry of HSL into droplet → more breakdown
What reaction allows for the Lipogenesis of Triacylglycerol in Enterocytes? (For formation of chylomicrons)
*Resynthesis after microvili uptake occurs in the ER → Chylomicrons
Step 1: activation by CoA via Acyl-CoA Synthetase
- Fatty acid (hydrocarbon chain-COO-) + ATP → PPi + Adds adenosine-phosphate (R-COO-PO4- - Adenosine)
*PPi Hydrolyzed to 2Pi (drives this step)
- Add in H-SCoA → AMP + Acyl-CoA
*All catalysed by Acyl-CoA Synthetase
Step 2: the 2-monoacylglycerol pathway
- 2-monoacylglycerol (from diet) → addition of acyl group wth acyl-CoA {MGAT} → Diacylglycerol → addition of acyl {DGAT} → Traicylglycerol → Chylomicrons for circulation
MGAT = 2-monoglycerol acyltransferase
DGAT = diacylglycerol acyltransferase
Explain the step of activation by CoA via Acyl-CoA Synthetase step for resynthesis of triacylglycerol.
- Fatty acid + ATP
- O- from COO- of fatty acid attacks ATP at P → FattyAcid - P - Adenosine + PPi
- PPi + H2O → 2Pi (exergonic, drives the reaction)
- Aceyladenylate mized anydride (FattyAcid - P - Adenosine) + H-SCoA → Acyl-CoA + AMP
*Fatty acid ends up just going on the CoA, leaving behind AMP
In which organs does De Novo Lipogenesis occurs?
- Adipose cells
- Liver cells
What are the steps of de novo Synthesis of Triacylglycerol?
*Glycerol-3-phosphate pathway (liver and adipocytes)
Step 1 → Generating Glycerol-3-Phosphate (2 options)
- DHAP synthesis (→ reduce → Gly3P)
- Phosphorylation of Glycerol (adipocytes lack glycerol kinase, mostly in the liver → fructose metabolism)
Step 2 → Adding Acyl-CoAs (from Acyl-CoA synthetase) x 2
- {GPAT} = Glycerol-3-phosphate acyltransferase
- {AGPAT} = 1-acylglycerol-3-phosphate acyltransferase
Step 3 → Dephosphorylation
Step 4 → Adding Aceyl-CoA (last and third one, could not add before because the site of addition was phosphorylated)
Which enzyme is the key regulator of de novo synthesis of Triacylglycerol?
Why is it important?
Lipin → regulates dephosphorylation (step 3)
Phosphatidic acid (Diacylglycerol-3-phosphate) is a branch point, can go to phospholipid synthesis of triacylglycerol
Lipin hydrolyzes Phosphatidic acid → DAG (1,2-Diacylglycerol) → makes the site available for the addition of the 3rd acyl group from Acyl-CoA
Which hormone stimulates conversion of glucose to fatty acid in adipose tissue?
(Lipogenesis)
How does it do so?
Insulin → via Transcriptional Control downstream of Insulin Receptor Tyrosine Kinase
What are the 3 main categories of membrane lipids?
- Phospholipids → Alcohol head group + phosphate (charged) + Glycerol bacbone + 2 FA chains
- ex: Phosphatidylcholine
- Sphingomyelin = Choline + Phosphate + (Amide bond) + Spingosine backbone + 1x FA chain - Glycolipids → Galactose head group (polar) + Sphingosine + 1x FA chain
- Sterols
- ex: Cholesterol
Which 3 enzymes are responsible for movement of membrane lipids within the membrane?
*In/Out Asymetry of the membrane
- Flippase: Out → In (ATPase)
- Floppase: In → Out (ABC transporter)
- Scramblase → random, down the concentration gradient
What are the2 types of microdomains and their characteristics?
RAFTs:
- Thick and stiff
- Made of Gangliosides, Sphingomyelin, Cholesterol
NON-RAFTs:
- Thin and Fluid
- Glycerophospholipids (PC, PS, PE)
*Some protein work better in RAFTs microdomains, some in non-RAFTs
What are 2 examples of important signaling membrane lipids?
PI (Phosphatidylinositol)
PIP2 → PIP3 by PI3 kinase activity OR IP3 by Phospholipase C
Under which circumstances should phospholipid synthesis be favoured?
- When cells are dividing (PPP)
- To maintain membrane rafts balance
- In case of stress, to provide signaling molecules
*By regulation of Lipin, when inhibited, pathway goes to PL biosynthesis
Where in the cell are phospholipids synthesized?
In the Endoplasmic Reticulum
*Phospholipid and neutral lipid biosynthesis
What are the steps for synthesis of PI, PG and Cardiolipin? (Glycerophospholipids)
Step 1: Activation of phosphatidic acid → CDP-diacylglycerol (high-energy intermediate)
- driven by hydrolysis of PPi → 2Pi
- Substrate = CTP + Phosphatidic acid
- Enzyme = CDP-diacylglycerol synthase
- Overall irreversible
Step 2: Adding Inositol or Glycerol-3-P
- {PI synthase} → Phosphatidylinositol
- {PG-3-P synthase} → {PG-3-P phosphatase} → PG → {Cardiolipin synthase} → Cardiolipin
- Produces CMP as a by-product
What is the Kennedy Pathway?
*For PE and PC, in all cell types
Step 1: Priming the head group with ATP → high-energy intemediate
Step 2: Activating the head group → using CTP → PPi
Step 3: Adding 1,2-diacylglycerol → produces CMP as by-product
What is an alternate pathway for synthesis of PC from PE in the liver specifically?
*The one-carbon pathway → Methylation via PEMT in the liver
PEMT = Phosphatidylethanolamine methyltransferase
~ 30% of total PC production in liver
Start with PE - NH3+
Step 1: Adding 1 methyl group
Step 2: Repeat
Step 3: Repeat
Finish with PC - NCH3
High-energy intermediate = S-Adenosyl-L-methionine (ATP + Methionine → release 3x Phosphates hydrolyzed) → to add the methyl group
Which function is highly dependent on abundant PC production in the liver?
Bile production → Need the perfect ration of Water : Cholesterol : bilee salts : Phosphatidylcholine
*Micellar phase is a very small range
If we don’t have the good ratio, the bile crystalizes → gallstones
What phenotype is observed in case of PEMT deficiency?
Enlarged liver du to accumulation of lipids (PC can’t be secreted in bile)
What occurs in PE → PS Transferase and PS → PE Decarboxylase?
Phosphatidylehtanolamine + Serine → {transferase} → Phosphatidylserine
*Positive NH3+ → Negative COO- terminal
Decarboxylase releases CO2 and reverse
What are the steps for synthesis of Sphingolipids?
*Sphingolipids = FA + Sphingosine chains + phosphate + Alcohol head group
Step 1: Adding an actviated acyl to the serin backbone
- Palmitoyl-CoA + Serine → Ceramide (releases CoA-SH)
Step 2a: Transfering a phosphocholine (phosphate + O-Choline) head group
- Ceramide → Sphingomyelin
Step 2b: Adding a glucose head group
- Ceramide → Cerebroside (a glycosphigolipid)
What are the roles of phospholipases?
*Mostly found in plasma mebrane
Role: Cleave phospholipids
- To generate signaling molecules (PLC in Gas-coupled pathway)
- To convert phospholipids
- To modulate the shape of the plasma membrane (cleaing a FA chain → invagination/exvagination because of cone shape)
What is Nieman-Pick Type A/B disease?
Deficiency in Sphingomyelinase (a phospholipase)
What is the Land’s Cycle?
Phospholipids → {Phospholipase, frees 1x FA} → Lysophospholipids (1 FA chain) → {Lysophospholipid acyltransferase, requiers Acyl-CoA}
*Affects membrane structure → invagination and evaginations
In Sphingolipids, wheat type of linkages is found between the Sphingosine tail and the phophate group?
Amide linkage
What is the difference between phosphoceramide and sphingomyelin?
Phosphoceramide = Spingosine + Phosphate + OH head group
Sphingomyelin = Sphingosine + Phosphate + Choline head group
Which 2 fatty acid tails are found in glycerolipids?
Glycerolipids = 2 tails + head = Phosphatidyl-(name of head group)
Palmitate (saturated) + Oleate (trans-unsaturated)
