Lipids Flashcards
What are lipids?
Heterogeneous organic molecules.
Are lipids soluble in water?
No.
Are lipids soluble in organic solvents?
Yes.
What are lipids soluble in?
Organic solvents.
Where do lipids exist?
Cell membranes
Lipid droplets in adipose tissue
Lipoproteins in blood
What do lipids exist as in adipose tissue?
Lipid droplets.
What do lipids exist as in the blood?
Lipoproteins.
What are the functions of lipids?
Stored form of energy Structural element of membranes Hormones Signalling molecules Enzyme cofactors Vitamins (needed for ADEK function)
What can lipids store?
Energy.
What can lipids act as a structural element of?
Cell membranes.
What can lipids act as a cofactor for?
Enzymes.
What can lipids work as to signal responses?
Hormones / signalling molecules.
What vitamin functions are lipids required for?
Function of ADEK vitamins.
What do lipid classifications include?
Fatty acids, triaceylglycerols, phospholipids, glycolipids and steroids.
What can imbalances/deficiencies in lipid metabolism lead to?
Major clinical problems such as atherosclerosis, obesity and metabolic disorder.
What are the 2 types of fatty acid?
Saturated
Unsaturated
What characterises saturated fatty acids?
No C=C bonds, straight chains, solids.
What characterises unsaturated fatty acids?
C=C bonds, kinked chains, liquids.
What is fatty acid nomenclature based on?
Number of carbons and bond positioning.
What are ‘good’/’bad’ fatty acids based on?
Saturation.
What are good fatty acids high in?
Polyunsaturated fats.
What are bad fatty acids high in?
Saturated fats.
What do very bad fatty acids result from?
Hydrogenation of vegetable oils.
What are essential fatty acids?
Essential fatty acids are those which must be ingested in the diet- they are linolenic acids from plants.
What are essential fatty acids called?
Linolenic acids.
What are linolenic acids derived from?
Plants.
Why must essential fatty acids be ingested?
Humans cannot introduce C=C bonds past carbon 9.
What are omega-3 fatty acids?
Essential fatty acids which are derived from linolenic acid and work to lower cholesterol and prevent CVDs.
What do deficiencies in essential fatty acids cause?
Chronic intestinal disease
Growth retardation
Depression
ADHD
What are triaceylglycerols?
Esters of fatty acids and glycerol.
How are triaceylglycerols formed?
Esterification.
What charge do triaceylglycerols have?
Neutral / no charge.
What do water-insoluble TAGs disperse as in the adipose tissue?
Lipid droplets.
What are triaceyglycerols used for?
Dietary fuel and insulation.
What are phospholipids composed of?
Glycerol bonded to 2 fatty acids and a phosphate head.
Why are phospholipids described as being amphipathic?
Dual hydrophilic/hydrophobic nature- the ionic phosphate head is hydrophilic whilst the fatty acid chains are hydrophobic.
What is the main dietary lipid?
Triaceylglycerol (TAG).
What other dietary lipids are there?
Phospholipids, cholesterol, cholesterol esters and free fatty acids.
What is the main site of lipid digestion.
Small intestine.
How are lipids initially digested?
Pancreatic lipase.
What is digestion of lipids by pancreatic lipase promoted by?
Emulsification.
What is emulsification?
Dispersion/mixing.
What are the 2 contributing factors to emulsification which promote lipid digestion?
Bile salts
Peristalsis
What are bile salts?
Biological detergents- prevent lipids from coalescing in aqueous environments.
What do TAG form following digestion with pancreatic lipase?
Monoaceylglycerol and 2 fatty acids.
What do cholesterol esters form following digestion with pancreatic lipase?
Cholesterol and 1 free fatty acid.
What happens to phospholipids during digestion with pancreatic lipase?
Hydrolysed to lysophospholipids.
What are lysophospholipids?
Product of phospholipid hydrolysis during digestion with pancreatic lipase.
What do digested lipids form?
Mixed micelles with bile salts.
What are mixed micelles?
Aggregates of digested lipids and bile salts following digestion with pancreatic lipase.
How do mixed micelles act?
Mixed micelles approach membranes and release lipid products through diffusion.
How do mixed micelles release lipid products at the cell membrane?
Diffusion.
What is steatorrhea?
Lipid malabsorption due to defects in bile secretion, pancreatic function or intestinal cell uptake.
What can cause steatorrhea?
Defects in:
Bile secretion
Pancreatic function
Intestinal cell uptake
What does steatorrhea result in?
Excess fat in faeces- stools float due to lipid mass, have an oily appearance and are foul smelling.
How can gallbladder removal affect lipid malabsorption?
Gallbladder secretes bile- removal inhibits lipid digestion and absorption of fats which can cause steatorrhea.
What do intestinal cells do?
Resynthesise TAG / PL / CE for export.
What resynthesises TAG / PL / CE for export?
Intestinal cells.
How do intestinal cells resynthesise TAG/PL/CE for export?
Package them with apoB-48 solubilising protein into chylomicrons.
What is apoB-48?
Solubilising protein which lipids are packaged with into chylomicrons forming digestion.
What are chylomicrons?
Packages of lipids and solubilising protein (apoB-48).
How are chylomicrons released?
Released through exocytosis into lymph and then the blood.
What happens to TAG in chylomicrons when they reach tissue?
Hydrolysed by lipoprotein lipase into fatty acids and glycerol.
What hydrolyses TAG in chylomicrons when they reach tissue?
Lipoprotein lipase.
What reaction occurs between lipoprotein lipase and TAG in chylomicrons when they react tissues?
Hydrolysis.
What happens to the fatty acids after they are separated from the chylomicron TAG in tissues?
Used for energy or re-esterified to TAG for storage.
What happens to the glycerol after it is separated from the chylomicron TAG in tissues?
Used in glycolytic processes.
What happens to chylomicrons depleted of TAG when they reach tissues?
Go to the liver as chylomicron remnants.
How does TAG exist in adipose cells?
Lipid droplets.
How are fatty acids released from stored TAG in adipose cells?
Hormone-sensitive lipase is activated by phosphorylation in response to epinephrine which releases FA.
What is HSL?
Hormone-sensitive lipase.
What is HSL activated and inactivated by?
Activated by phosphorylation in response to epinephrine which releases the fatty acids from TAG lipid droplets. Increased blood glucose or insulin inhibits the phosphorylation.
How are free fatty acids transported in the blood?
In complex with serum albumin.
What is the most abundant plasma protein?
Albumin.
What does serum albumin allow and how?
Travel of free fatty acids in the blood- has binding sites for them.
What happens to most fatty acids?
Esterified and travel in lipoproteins (HDL/LDL etc).
What are lipoproteins?
Proteins with lipid attachments- have hydrophobic cores (TAG/CE) and hydrophilic surfaces (cholesterol, PL).
What are lipoproteins classified according to?
Density.
What is VLDL?
TAG from the liver to tissues.
What does LDL do?
Transports cholesterol to extrahepatic tissues (NOT LIVER)
What does HDL do?
Transports cholesterol to hepatic tissues (LIVER).
Why is HDL good?
Removes cholesterol for excretion and prevents excess buildup.
Why is LDL bad?
Can lead to an increased build-up of cholesterol and subsequent deposition of plaques in blood vessels.
What is atherosclerosis?
Atherosclerosis is the formation of plaques on vascular arteries- these can build up and result in clots and embolism which have high cardiovascular risks.
What process is used to oxidise fatty acids as fuels?
Beta-oxidation.
What is beta-oxidation?
The process used to oxidise fatty acids as fuel molecules.
How does beta-oxidation work?
Degrades fatty acids 2C at a time- produces energy sources.
In what structure does beta-oxidation degrade fatty acid molecules?
Degrades them 2C at a time.
What does beta-oxidation produce?
Acetyl CoA
NADH/FADH2
Where does beta-oxidation occur?
Mitochondrial matrix.
What are the 3 stages of beta-oxidation?
Activation of fatty acids
Transport into mitochondria
Degradation into energy sources
What can the products of beta-oxidation be used in?
Energy production.
What happens in the first stage of beta-oxidation?
Fatty acids are activated to form fatty acyl CoA in the cytoplasm.
Where does fatty acid activation occur?
Cytosol.
What do activated fatty acids form?
Fatty acyl CoA.
Where do activated fatty acids need to be for beta-oxidation to occur?
Mitochondrial matrix.
How do short and medium chain fatty acids reach the mitochondrial matrix for beta-oxidation?
Diffuse freely.
How do long chain fatty acids reach the mitochondrial matrix reach the mitochondrial matrix for beta-oxidation?
Carnitine shuttle.
What is the carnitine shuttle?
A shuttle used to let activated fatty acids in the cytosol reach the mitochondrial matrix for beta-oxidation.
How does the carnitine shuttle work?
CPT1 exchanges carnitine for the CoA group to form a conjugate which can be transported through the matrix. In the matrix, CPT2 exchanges CoA for the carnitine group to produce fatty acyl CoA again, ready for oxidation.
What molecules exchange carnitine for CoA groups?
CPTI, CPTII
What does the FA enter the matrix as?
Fatty acid conjugate with carnitine.
How is the FA conjugate transported into the matrix?
Transporter protein.
What happens to free carnitine in the matrix?
It is shuttled back out in order to maintain free cytoplasmic supply and allow the process to continue as required.
What is the carnitine shuttle regulated by?
Malonyl CoA.
How does malonyl CoA regulate the carnitine shuttle?
Has ability to inhibit the process to prevent simultaneous synthesis and degradation.
Why might malonyl CoA inhibit the carnitine shuttle?
To prevent simultaneous synthesis and degradation.
How is carnitine obtained in the body?
Found in diet- can also be produced by the liver and kidneys.
What do carnitine deficiencies lead to?
No beta-oxidation happening- leads to hypoglycaemia.
How is carnitine-deficient linked hypoglycaemia treated?
Administration of intravenous glucose or a short/medium chain fatty acid that doesn’t need carnitine shuttle.
What are the 4 steps of beta-oxidation degradation?
Dehydrogenation- produces FADH2
Hydration
Dehydrogenation- produces NADH
Thiolysis- cleaved to produce acetyl CoA
What happens in the first dehydrogenation within degradation?
Production of FADH2.
What happens in the second dehydrogenation within degradation?
Production of NADH.
What happens in the thiolysis stage of degradation in beta-oxidation?
Cleavage to produce acetyl CoA.
What does each cycle of beta-oxidation produce?
1 Acetyl CoA
A species 2C shorter than the original
129 ATP
How much ATP does beta-oxidation yield?
129ATP
Why are fatty acids more efficient fuels than glucose?
Production of 129 ATP compared to 2/32 ATP.
What happens to very long chain fatty acids in excess of 22C?
Preliminary oxidation in the peroxisome- they are then transported to the mitochondrial matrix.
Where does preliminary oxidation of very long chain fatty acids occur? (>22C)
Peroxisome.
Why is preliminary oxidation in the peroxisome less efficient than normal beta-oxidation?
First step doesn’t produce FADH2.
What happens to preliminary oxidised fatty acids?
Transported to the mitochondrial matrix for normal beta-oxidation.
What do defects in the preliminary oxidation pathway result in?
Build-up of long chain fatty acids in the bloodstream.
Can fatty acids by converted to glucose?
No- they are not gluconeogenetic because of the thermodynamically irreversible step converting pyruvate to acetyl CoA.
Why are fatty acids non-gluconeogenetic?
Cannot bypass the thermodynamically irreversible step converting pyruvate to acetyl CoA.
When is the liver flooded with excess acetyl CoA from fatty acid breakdown?
During fasting or starvation.
What can excess acetyl CoA be converted into?
Ketone bodies.
What are ketone bodies?
Water-soluble transporters of acetyl CoA.
What is the process of acetyl CoA conversion into ketone bodies called?
Ketonegenesis.
Why are ketone bodies good?
They can be utilised as an energy source.
When is the use of ketone bodies as an energy source particularly useful?
In systems that cannot use fatty acids as an energy source (e.g. cardiac/brain/skeletal muscle).
Where are ketone bodies formed?
Liver matrix.
Where do ketone bodies go after formation in the liver?
Transported in the blood to tissues as required as they are soluble.
What is the rate of ketonegenesis dependent on?
The free availability of acetyl CoA.
Can the liver use ketone bodies?
No- it can make them but not use them.
Why is excessive ketonegenesis bad?
Can cause a range of clinical issues due to induced ketoacidosis.
What diagnostics show excessive ketonegenesis?
Ketonaemia (blood KB)
Keonuria (blood urine)
Acidemia
What are excessive ketone bodies characterised by?
Fruity odour in the breath.
What are ketone bodies a breakdown product of?
Acetone.
What does acetone cause?
Distinguishing fruity odour in the breath.
In what conditions is excessive ketonegenesis often seen?
Uncontrolled diabetes
Starvation
How are fatty acids obtained in the body?
Essential fatty acids in diet
Synthesis in body
Where are fatty acids synthesised?
Liver
Lactating mammary gland
Adipose tissue
What does fatty acid synthesis require?
Acetyl CoA
NADPH
ATP
Where in the cell does fatty acid synthesis occur?
Cytosol.
Where must acetyl CoA be for fatty acid synthesis?
Cytosol- must be transported from the mitochondrial matrix following glycolytic production.
What transports acetyl CoA from the mitochondrial matrix to the cytosol for fatty acid synthesis?
Citrate shuttle.
What activates the citrate shuttle?
High mitochondrial citrate concentration.
What enzymes are involved in fatty acid synthesis?
Acetyl CoA carboxylase
Fatty acid synthase
What is the product of fatty acid synthesis?
Palmitate.
What is the first reaction in fatty acid synthesis?
Acetyl CoA > Malonyl CoA
What is acetyl CoA to malonyl CoA catalysed by?
Acetyl CoA carboxylase.
What does acetyl CoA carboxylase catalyse?
Conversion of acetyl CoA to malonyl CoA.
What is acetyl CoA carboxylase activity controlled by?
ACC.
How does ACC control work?
Activated by citrate
Deactivated by palmitoyl CoA
Activated by insulin, deactivated by epinephrine/glucagon
How does fatty acid synthesis occur after the conversion of acetyl CoA to malonyl CoA?
Multistep process with a multi-functioning enzyme.
What is the general reaction for fatty acid synthesis?
Acetyl CoA + Malonyl CoA > Palmitate
How many NADPH are required for palmitate synthesis?
14.
Where does the NADPH come from in fatty acid synthesis?
Derived from the pentose-phosphate pathway.
What does the synthesis of palmitate use up?
Carbon dioxide.
Where does any further modification of palmitate or dietary fatty acids occur?
Mitochondria / ER with diverse range of enzymes.
Can fatty acid synthesis and degradation occur at the same time?
No.
What are steroid hormones?
Chemicals that serve as messengers.
What are steroid hormones characterised by?
Steroid ring.
What is cholesterol?
Cell membrane component.
Where is cholesterol synthesised?
Liver- dietary meats.
What drug is cholesterol controlled by?
Statins.
What are eicosanoids?
Signalling molecules derived from 20C eicosanoid acids.
What are eicosanoids the precursor for?
Prostaglandins
Thromboxanes
Leukotrienes
What do prostaglandins link with?
Link with pain and fever.
What do thromboxjnes link with?
Blood clotting pathways.
What do leukotrienes link with?
Bronchioconstriction / smooth muscle contraction.
