Lipids Flashcards
What are lipids and what are their functions?
Lipids are heterogeneous organic molecules that exist in a few different forms and several purposes. They are:
o A stored form of energy
o A structural component of cell membranes
o Needed as enzyme cofactors
o Used in hormones
o Used for the synthesis of Vitamins A D E and K
o Used as signalling molecules
Describe briefly the major classes of lipids
Fatty acids - hydrocarbon chains with a carboxylic acid group at one end. They can be saturated or unsaturated
Triacylglycerols - esters of fatty acids and glycerol. They are water insoluble, make up adipose tissue
Phospholipids -glycerol bonded to two fatty acids and a phosphate group. They are amphipathic and form the basic structure of the cell membrane
Glycolipids
Steroids
Define essential fatty acids
Essential fatty acids, or EFAs, are fatty acids that humans and other animals must ingest because the body requires them for good health but cannot synthesize them
What is the main dietary lipid?
Triacylglycerol
Describe some differences between saturated and unsaturated fatty acids
Unsaturated FA – one or more double bonds that kink the hydrocarbon chain, loosely packed together, liquid, Van der Waals forces relatively weak, low melting point
Saturated FA - are solid, no double bonds, are able to align closely packed, Van der Waals forces between molecules are strong, high melting point
Give an example of a essential fatty acid
Linoleic and a-linolenic acid
What is linoleic a substrate for?
Prostaglandins
What is linolenic acid a substrate for?
Omega 3 fatty acids and arachidonic acid
What are the health benefits of omega 3 fatty acids?
Omega-3 FA lowers plasma cholesterol and prevents atherosclerosis, lowers TAG and therefore prevents obesity.
What conditions arise due a deficiency in omega 3 fatty acids?
Essential fatty acid deficiency
Chronic intestinal diseases
Depression
Attention deficit hyperactivity disorder
What are the symptoms of essential fatty acid deficiency?
Essential fatty acid deficiency - growth retardation, reproductive failures, kidney and liver disorders, subtle neurological and visual problems
Describe the structure and function of triacylglycerols
- Esters of FAs and glycerol
- Esters are neutral uncharged lipids
- Water insoluble TAG coalesce into lipid droplets in adipose tissue (major lipid component of adipose tissue)
- Dietary fuel and insulation
Describe the structure and function of phospholipids
• Composed of glycerol bonded to two fatty acids and a phosphate group.
• Amphipathic - charged phosphate group ‘head’ of a phospholipid is hydrophilic (attracted to water) whereas the hydrophobic ‘tails’ repel water.
Make up cell membranes
Describe the structure of sphingolipids
2FA and a sphingosine head
Involved in signal transmission and cell recognition
Where is the main site of lipid digestion?
Small intestine
What is lipid digestion by pancreatic lipase enhanced by?
Emulsificationby bile salts and peristalsis
Where does digestion of lipids start?
In the stomach by acid lipase, which digests short chain lipase, such as those in milk (important in neonates)
What reaction does pancreatic lipase catalyse?
TAG = monoacylglycerol + two fatty acids
What are cholesterol esters broken down into?
- Cholesterol esters make up 15% of dietary lipids
* Cholesterol esters digested to cholesterol + free FA
What are the results of phospholipid digestion?
- Phospholipids hydrolysed to FA and lysophospholipid
* Lysophospholipids are small bioactive lipid molecules characterized by a single carbon chain and a polar head group.
What is a micelle?
A micelle is an aggregate of surfactant molecules dispersed in a liquid colloid. A typical micelle in aqueous solution forms an aggregate with the hydrophilic “head” regions in contact with surrounding solvent (e.g. ampiphatic bile salts) , sequestering the hydrophobic single-tail regions in the micelle centre (e.g. fats).
What is steatorrhea?
- Lipid malabsorption due to defects in bile secretion by the gallbladder, pancreatic function or intestinal cell uptake results in steatorrhea
- Steatorrhea is excess fat in faeces. Stools float due to excess lipid, have an oily appearance and are foul smelling. CF patients prone to this
What are chylomicrons?
• Intestinal cells resynthesize TAG, PL, CE for export
• Insoluble so packaged with apoB-48 (solubilising protein) into chylomicrons for export
• Chylomicrons are lipoprotein particles that consist of triglycerides, phospholipids, cholesterol, and proteins. They transport dietary lipids from the intestines to other locations in the body.
• Chylomicrons are released by exocytosis into lymph then blood
(cholesterol + TAG + protein)
How are fatty acids released from stored adipose tissue when needed e.g. during starvation or exhaustion of other energy stores?
- FA released from stored TAG by hormone sensitive lipase (HSL), coupled to a Gas GPCR
- HSL activated by phosphorylation in response to epinephrine
- High plasma glucose and insulin promote dephosphorylation (inactivation) of lipase
How are unesterfied fatty acids transported in the blood?
With albumin, 2-7 binding sites for FAs
How are esterified fatty acids transported in the blood?
Carried in lipoproteins (90% FAs are esterified)
Describe the different lipoprotein classes
- Chylomicrons – largest, TAG rich (transport TAG from intestines to tissues), least dense hence largest diameter
- VLDL – large, TAG rich (TAG from liver to tissues), low density
- LDL – small, cholesterol rich (transport cholesterol to extrahepatic tissue, “bad cholesterol”
- HDL – smallest, protein and cholesterol rich (transport cholesterol from tissue to liver for elimination), most dense hence smallest diameter
Which lipoprotein is often associated with atherosclerosis?
LDL, forms fatty streaks and plaques
Due to obesity or LDL receptor genetic defects
What enzyme is responsible for fatty acid activation in stage 1 of beta oxidation?
Acyl CoA synthase
How do activated fatty acids in the cytoplasm enter the mitochondria?
Carnitine shuttle (with aid of translocase and carnitine palmitoyl acyltransferase I and II)
Stage 2 of beta oxidation - transportation
How many ATP molecules are formed from FADH2?
2
How many ATP molecules are formed from NADH?
3
How many ATP molecules are formed from acetyl CoA?
8
What is the role of the peroxisome in beta oxidation?
- Very-long chain fatty acids >22 carbons undergo a preliminary beta-oxidation in peroxisomes.
- First step does not produce FADH2 and so less energy efficient
- The shortened FA linked to carnitine diffuses from peroxisome into the mitochondria for further oxidation.
What can excess acetyl CoA be converted into during fasting or starvation?
Ketone bodies, water soluble transporters of acetyl CoA for other tissues in need
What are ketone bodies used for?
- Ketone bodies are water-soluble transporters of Acetyl-CoA, which can be converted back and enter CAC
- Ketone bodies made in liver supply energy during fasting (normal physiological role)
- Cardiac and skeletal muscles use ketone bodies as an energy source.
- Ketone bodies can fuel tissues, such as brain cells, during starvation (brain cannot use FA as fuel source)
Name two important ketones
acetoacetate and beta-hydroxybutyrate
Where does fatty acid synthesis take place in the body?
- Liver
- Lactating mammary gland
- (Adipose tissue)
Where do we get fatty acids?
Diet (only essential fatty acids)
Synthesis from excess CHO and protein components
Where does fatty acid synthesis take place in cell?
Cytosol
How does acetyl CoA reach cytosol from the mitochondria?
Citrate shuttle
What is cholesterol used for in the body?
Component of cell membranes
Precursor to other molecules (sterols, vit D, bile acids)
What enzyme catalyses the rate limiting step of cholesterol biosynthesis?
HMG-CoA reductase
What do statins inhibit?
- Inhibit HMG-CoA reductase that is essential in cholesterol synthesis
- Lower LDL levels
- Improve risk of developing cardiovascular disease (MI, IHD)
What are eicosanoids?
- Signaling molecules derived from omega-3 or omega-6 fatty acids.
- Precursors to prostaglandins, thromboxanes, and leukotrienes.
- Exert control over inflammation or immunity, and as messengers in the central nervous
What do eicosanoids regulate?
- Inflammatory response (joints, skin, eyes)
- Pain and fever (Prostaglandins)
- Blood pressure regulation (prostacyclin)
- Blood clotting induction (thromboxanes)
- Many reproductive functions (e.g. labour induction) & menstrual cramps (prostaglandins)
- Sleep/wake cycle
What drugs mimic eicosanoids?
COX inhibitors (inhibit prostaglandin production) Leukotriene antagonists e.g. Montelukast, Zafirlukast
What do prostaglandins regulate?
Pain, fever, reproductive function (labour induction and menstrual cramps)
What do thromboxanes regulate?
Blood clotting
What do prostacyclin regulate?
Blood pressure
Describe in outline the process of lipid digestion and absorption
Lipases, bile and peristalsis break down lipids in SI
Free FAs then packages into mixed micelles
Intestinal mucosal cells absorb them from GI tract into blood stream and lymphatics
Chylomicrons and other lipoproteins are formed to transport them to peripheral tissues which can pick up fatty acids by lipoprotein lipase and tissue picks them up and stores them as adipose.
Tissue can then release fatty acids when needed via hormone sensitive lipase.
Describe how lipids are transported in the body and the role of lipoproteins in this process
As lipids are hydrophobic they are packaged with proteins such as apoB-48 to form chylomicrons to allow export and transport of lipids to other locations in the body. Also as VLDL, LDL and HDL lipoproteins, and a little binds albumin.
When they reach the target tissue, TAGs in chylomicrons are hydrolysed to FA and glycerol by lipoprotein lipase found in skeletal muscle and adipose tissue. FA used for energy or re-esterified for storage, while glycerol goes along with chylomicron remnants to the liver for glycolysis or gluconeogenesis.
Describe the synthesis of free fatty acids
Break down of TAGs, cholesterol esters etc
Can be synthesised from excess acetyl CoA in liver
Describe briefly the catabolism of fatty acids by beta oxidation
Degrades fatty acids two carbons at a time
Produces acetyl CoA, NADH and FADH2 for ATP production
Occurs in mitochondrial matrix
Three stages:
- Activation of FA to FA-CoA in cytosol by acyl-CoA synthase
- Transport into mitochondria (carnitine shuttle + translocase)
- Degradation of two carbon fragments as acetyl CoA in matrix (4 steps: dehydrogenation, hydration, dehydrogenation and thiolysis)
Describe the carnitine shuttle
Fatty acyl CoA crosses first membrane following conversion to fatty acyl-CoA by Acyl-CoA synthase and transport by translocase
Is then converted to fatty acid-carnitine via carnitine-palmitoyt transferase I to allow its passage over inner membrane by translocase
Fatty acid then splits from carnitine by carnitine palmitoyl transferase II
Describe the function, synthesis and metabolism of ketone bodies
Water soluble transporters of acetyl CoA during starvation
Made in the mitochondrial matrix by the liver then released into blood to reach target tissues
Once at tissue they are reconverted by beta-ketoacyl-CoA transferase (thiophorase) into acetyl CoA
What are the citrate and carnitine shuttle used for?
Citrate shuttle - acetyl CoA from mitochondrial matrix to cytosol for fatty acid synthesis
Carnitine shuttle - transports long chain FAs into mitochondrial matrix for beta oxidation
What is required for fatty acid synthesis and what is produced?
Enzymes -acetyl CoA carboxylase, fatty acid synthase
Acetyl CoA
NADPH
Produces palmitic acid
What is the committed step in fatty acid synthesis?
1 st step - activation step involving the formation of malonyl CoA by acetyl CoA carboxylase
What signals regulate the enzyme in the committed step of fatty acid synthesis?
Enzyme - acetyl CoA carboxylase
Activated by citrate and insulin
Deactivated by palmitoyl CoA (end product) and glucagon and epinephrine
Briefly outline the steps of fatty acid synthesis
Activation - committed, acetyl CoA to malonyl CoA
Elongation by acyl-malonyl ACP
Reduction - dehydration - reduction
Fatty acid cleavage to remove ACP
Briefly outline the steps of fatty acid synthesis
Activation - committed, acetyl CoA to malonyl CoA
Elongation by acyl-malonyl ACP
Condensation - reduction - dehydration - reduction
Fatty acid cleavage to remove ACP
What enzyme is involved in the rate limiting step of cholesterol biosynthesis?
HMG-CoA reductase (HMGR) - target of statins
What enzyme is involved in the rate limiting step of cholesterol biosynthesis?
HMG-CoA reductase (HMGR) - target of statins to lower LDLs
