Lipids Flashcards
What are lipids?
Heterogeneous organic molecules
Insoluble in water (hydrophobic), soluble in organic solvents
Where do lipids exist?
Exist in cell membranes, as lipid droplets in adipose tissue, in blood lipoproteins
Biological functions of lipids
- Stored form of energy
- Structural element of membranes
- Enzyme cofactors
- Steroid Hormones
- Vitamins A,D,E,K
- Signalling molecules
What are the major lipid classes?
- Fatty acids
- Triacylglycerol
- Phospholipid
- Glycolipids
- Steroid
What are fatty acids?
Fatty acids are carboxylic acids that are structural components of fats, oils, and all other categories of lipids, except steroids.
Discuss the structure of fatty acids
Straight chain of an even number of carbon atoms, with hydrogen atoms along the length of the chain and at one end of the chain and a carboxyl group (―COOH) at the other end.
What is an unsaturated fatty acid?
One or more double bonds in hydrocarbon chain
What is a saturated fatty acid?
Are solid, no double bonds in hydrocarbon chain
What are essential fatty acids?
Fatty acids that our body cannot produce and we must get them from plants
What are the names of the essential fatty acids?
Linoleic acid (LA) - omega-6 family
Alpha linolenic acid (ALA) - omega-3 family
What are good fats?
(cardiovascular)
High in polyunsaturated fatty acids: e.g vegetable oils, like olive oil, sunflower oil, ect
What are bad fats?
(cardiovascular)
High in saturated fatty acids: (e.g stearic beef) (Saturated - huge role in myelination of nerve fibres and hormone production important in maintaining health)
What are really bad fats?
Trans fatty acids, result from hydrogenation of vegetable oils e.g hard margarine (man-made)
What does 18:0 mean?
Contains 18 carbons and no double bonds
What does 18:1 mean?
18 carbons and one double bond
What can humans not digest?
Humans cannot introduce double bonds beyond carbon 9
What is arachidonic acid?
A precursor of eicosanoids can be synthesized from linoleic acid
What are omega-3 fatty acids derived from?
Omega-3 fatty acids are derived from linolenic acid as essential FAs.
E.g., eicosapentaenoic and docosahexaenoic acid
What does omega 3-FA do?
Lowers plasma cholesterol prevents atherosclerosis, lowers TAG prevents obesity, reduces inflammation.
What does omega-6 FA do?
Omega-6 FA derived from linoleic areessential but not same benefits
What are triacylglycerols (TAG)?
Esters of FAs and glycerol
Esters are neutral uncharged lipids
Dietary fuel and insulation
Discuss TAG and water
Water insoluble TAG coalesce into lipid droplets in adipose tissue (major lipid component of adipose tissue)
What are phospholipids?
Composed of glycerol bonded to two fatty acids and a phosphate group.
What is the main dietary lipid?
Triacylglycerol main dietary lipid
Where is the main site of lipid digestion?
Small intestine
What is lipid digestion by pancreatic enzymes (lipases) promoted by?
Promoted by emulsification (dispersion) by bile salts and peristalsis (mixing)
What are bile salts?
Bile salts are also biologic detergents that enable the body to excrete cholesterol and potentially toxic compounds (eg, bilirubin, drug metabolites).
What is the function of bile salts?
Solubilize ingested fat and fat-soluble vitamins, facilitating their digestion and absorption.
What effect does bile salts have?
Emulsification of lipids (breaks down fat globules into smaller droplets) - larger surface area for lipase to act on
Forms mixed micelles
What physical mechanism helps with protein digestion?
Peristalsis
What are bile salts derived of?
Cholesterol
What are micelles?
The end product of fat digestion is converted into these.
They are small water soluble droplets.
Fatty acid core and a polar surface
How do we digest triacyglycerols?
Most TAG degraded in small intestine by pancreatic lipase to monocyglycerol + two FA
How Do We Digest Cholesterol Esters?
Cholesterol esters digested to cholesterol and free FA
How do We Digest Phospholipids?
Phospholipids hydrolysed to FA and lysophospholipid.
What does lipid malabsorption cause?
Lipid malabsorption due to defects in bile secretion, pancreatic function or intestinal cell uptake results in steatorrhea.
What type of fatty acid chains do not need micelles for absorption?
Short and medium chain FA
What is steatorrhea?
Steatorrhea is excess fat in faeces. Stools float due to excess lipid, have an oily appearance and are foul smelling.
What secretes bile?
Gallbladder secretes bile. Removal of the gallbladder inhibits digestion and absorption of fats
What is a chylomicron?
A droplet of fat present in the blood or lymph after absorption from the small intestine.
Where is lipoprotein lipase?
Found primarily in capillaries of skeletal muscle and adipose tissue
What happens to free FA?
Resulting free FA used for energy or re-esterified to TAG for storage
What happens to chylomicrons depleted of TAG?
Called chylomicron remnants – go to liver
What is glycerol used for?
Glycerol is used by liver to produce glycerol-3-phosphate (glycolysis & gluconeogenesis)
Storage of TAG
In adipose cells TAG are stored as droplets that constitute the “depot fat”
Where are fatty acids released from?
Released from stored TAG by hormone sensitive lipase (HSL)
How is free fatty acid transported through blood?
In complex with serum albumin
Albumin most abundant plasma protein with 2-7 binding sites for FA
Most FA esterified (>90%)
These carried in lipoproteins
What are the hydrophobic cores of lipoproteins?
TGs, cholesteryl esters cores
What are the hydrophilic surfaces of lipoproteins?
Unesterified cholesterol, phospholipids , apolipoproteins e.g.B100
What is good cholesterol?
HDL
What is bad cholesterol?
LDL
What does B-oxidation of fatty acids do?
Degrades fatty acids to two carbons at a time
What does B-oxidation of fatty acids produce?
Acetyl CoA and NADH and FADH2 which are sources of energy (ATP)
What are the three stages in B-oxidation fatty acid?
- Activation of fatty acids in the cytosol
- Transport into the mitochondria
- Degradation to two carbon fragments as acetyl CoA in the mitochondrial matrix - energy
What is fatty acid activated to form?
B-oxidation
Fatty acid acyl CoA in cytoplasm.
How does long chain fatty acid acyl CoA get into mitochondrial matrix for oxidation?
Via citrate shuttle
Where is fatty acid transported to?
Transport activated fatty acid into the mitochondira, the inner mitchondrial matrix.
When does the citrate shuttle occur?
When citrate concentration in mitochondria is high
What happens once citrate is in the cytosol?
Citrate lyase releases the acetyl CoA and combines on a CoA part in the cytosol and forms oxaloacetate.
Aceytl CoA now in cytosol ready for fatty acid synthesis.
What enzymes are needed for fatty acid synthesis?
Acetyl CoA carboxylase (Activation/regulation - really important rate limiting step)
Fatty acid synthase (multifunctional enzyme)
What is CAT-1 needed for?
FA synthesis
Inhibited by malonyl CoA
What does the citrate shuttle prevent?
Prevents synthesis and degradation occuring simultaneously
Where do we get carnitine?
Carnitine from diet or made from lysine or methionine (liver/kidney)
Discuss CAT-1 deficiency
- No B-oxidation, hypoglycemia
- Coma on overnight fast
- Improved with IV glucose
- Therapy - give medium chain fatty acids that do not require CAT for mitochondrial transport
What is needed for the fatty acid to be synthesised?
Acetyl CoA
(NADH reduced to form) NADHP
What is the main product of fatty acid synthesis?
Palmitic acid (16 carbon fatty acid often called palmitate)
What activates acetyl-CoA carboxylase?
Citrate
Signals that there is enough glucose so make FA
What deactivates acetyl-CoA carboxylase?
Palmitoyl CoA
Enough FA made so halt synthesis
Gulcagon, epinephrine deactivates
Overall reaction for fatty acid synthesis
8 acetyl CoA + 14 NADPH + 14 H+ + 7ATP
——–>
Palmitate + 8 CoA + 14 NADP+ + 7ADP + 7P + 7H2O
Where does any further modification of palmitate or dietary FAs (unsaturation, elongation, branching) occur?
Occurs in mitochondria and ER by diverse enzymes
Can essential fatty acids be synthesised?
No but are required to make other lipids
Fate of fatty acid
Acetyl CoA –> Fatty Acid (liver) —> (glycerol -P) TAG –> (protein phospholipid cholesterol) –> VLDL –> Adipose tissue
Degradation of free fatty acid
- Dehydrogenation to produce FADH2
- aka oxidation FAD to FADH2 for ATP formation - Hydration
- Requires H2O
3.. Dehydrogenation to produce NADH
- aka oxidation NAD+ to NADH for ATP formation
- Thiolysis (cleaved) to produce acetyl CoA to feed into the TCA cycle
Energy formed during B-oxidation of fatty acids?
129
Where does B-oxidation of very long fatty acids happen?
Very long chain fatty acids» 22 carbons undergo a preliminary B-oxidation in peroxisomes
What are ketones?
Fuel molecules (good)
What happens during fasting or starvation?
Glucose is decreased and excess acetyl CoA from fat metabolism can be converted to ketone bodies
What use ketone bodies as energy?
-Cardiac and skeletal muscles
- Ketone bodies can fuel brain cells during starvation (brain cannot use FA as fuel source)
Where are ketone bodies formed?
In the liver (mitchondrial matrix) and is transported with the blood to other cells where it is used as fuel
Can the liver use ketone bodies?
Liver makes but cannot use ketone bodies
Ketone bodies and acetyl-CoA
Water soluable transporters of acetyl-CoA
What do excessive ketone bodies?
Uncontrolled diabetes or starvation leads to very high ketone body concentrations in the blood
When the rate of ketone body production exceeds utilisation, ketonemia (blood KB) ketonruia (urine KB) and acidemia results
Fruity odour in breath due to acetone results
What is diabetic ketosis when insulin was absent?
Decrease insulin, increased glucagon - increased lipolysis - increased free fatty acids in plasma - increased hepatic output of ketone bodies - increased ketoacidosis
Where can we get fatty acids from?
Our diet (essential)
Synthesis - from excess carbohydrate, fat and protein compounds (acetyl CoA)
Where does fatty acid synthesis occur?
Fatty Acid Synthesis occurs in:
- Liver
- Lactating mammary gland
- Adipose tissue
What are fatty acids synthesised from?
Acetyl CoA
What does the synthesis of fattu acid need?
Uses ATP and NADPH
What are the enzymes of fatty acid synthesis?
- Acetyl CoA carboxylase (Activation/regulation)
- Fatty acid synthase (multifunctional enzyme)
What is the product of fatty acid synthesis?
Palmitic acid
What metabolic and hormonal signals control the activity of acetyl-CoA carboxylase?
Acetyl-CoA carboxylases
ACC - key regulatory enzyme activated by citrate and deactivated by palmitoyl CoA - synthesises malonyl CoA
What activates Acetyl-CoA carboxylases?
Activated by citrate (signals that there is enough glucose - so makes FA)
Insulin activates glucagon
What deactivates Acetyl-CoA carboxylases?
Deactivated by palmitoyl CoA (enough fatty acid made so half synthesis)
Epinephrine deactivates
What forms acetoacetyl-ACP and what drives this reaction?
Acyl-malonyl ACP condensing (bond forming) enzyme forms acetoacetyl-ACP
This reaction is driven by the decarboxylation
Steps on reduction-dehydration-reduction
FA cleavage
Acyl carrier protein
14 NADPH for Palmitate Synthesis
Where does any further modification of palmitate or dietary Fas (e.g. unsaturation, elongation, branching) take place?
In mitochondria and ER by diverse enzymes
