week 3 lipids (revised) Flashcards
what are 5 the major lipid classes
- fatty acids
- triacylglycerols
- phospholipid
- glycolipid
- steroids
what kind of fatty acids are “good fats”
- high in polyunsaturated fatty acids
what kind of fatty acids are “bad fats”
- high in saturated fatty acids e.g. beef
- have a role in myelination and hormone production, important in maintaining health
what kind of fatty acids are “really bad fats”
- trans unsaturated fatty acids
- result from hydrogenation of veg. oils e.g. margarine (man-made)
what are essential fatty acids
- linoleic and alpha linoleic acids
- ones that you cannot make, must get them from diet
what can you make from linoleic acid (essential fatty acid)
- arachidonic acid is a precursor of Eicosanoids and can be made from linoleic acid
- omega 3 fatty acids derived from linoleic acids (lowers cholesterol and prevents atherosclerosis, lowers triacylglycerols, prevents obesity, reduces inflammation)
with happens if you have an essential acid deficiency
- rare, most often in infants with diets deficient in EFA
- signs are scaly dermatitis, alopecia, in children intellectual disability
- ADHD = lower levels of omega 3
- chronic intestinal disorders
- depression = deficiency of lipid signalling molecules
what are triacylglycerols
- major class of lipid
- esters of fatty acids and glycerol (esters are neutral uncharged lipids)
- water insoluble
- dietary fuel and insulation
what are phospholipids
- major class of lipids
- glycerol bound to two fatty acids and a phosphate group
- amphipathic (hydrophobic and hydrophilic)
what is the main site of digestion of lipids
small intestine
what is lipid digestion promoted by
- lipid digestion by pancreatic enzymes (lipases) is promoted by emulsification by bile salts and peristalsis (mixing)
what are bile salts
- act as biological detergents to form emulsions and mixed micelles
- stop lipids grouping together in aqueous environment
- derivatives of cholesterol
how are triacylglycerols digested
- most TAG are degraded in small intestine by pancreatic lipase to monoacylglycrol and 2 fatty acids
how are cholesterol esters and phospholipids digested
- cholesterol esters digested to cholesterol and free fatty acid
- phospholipids hydrolysed to fatty acid and lysophospholipid
what is the uptake of digested lipids
- products of lipid digestion form mixed micelles with bile salts
- mixed micelles approach the border of the enterocytes (intestinal cells) and release lipid products which enter cells by diffusion
- short and medium chain fatty acids do not require micelles for absorption
what is steatorrhea
- excess fat in faeces
- due to lipid malabsorption (defects in bile secretion, pancreatic function, or intestinal cell uptake, removal of gallbladder)
what happens to absorbed fatty acids
- intestinal cells resynthesise TAG, phospholipids and cholesterol esters for export
- insoluble so packaged into chylomicrons for export
- chylomicrons released by exocytosis into lymph then blood
what happens when blood chylomicrons reach tissue
- TAG in chylomicrons is hydrolysed to fatty acid and glycerol by lipoprotein lipase
- resulting free fatty acid used for energy or re-esterified to TAG for storage
- chylomicrons depleted of TAG are called chylomicron remnants and go to liver
- glycerol used by liver to produce glycerol-3-phosphate (glycolysis and gluconeogenesis)
what is the digestion of fats
- fats ingested
- bile salts emulsify fats in small intestine forming mixed micelles
- intestinal lipases degrade TAG
- fatty acids and breakdown products taken up by intestinal mucosa and converted into TAG
- TAG + cholesterol + apolipoproteins packaged into chylomicrons
- chylomicrons move through lymphatics first then blood
- lipoprotein lipase in capillary converts TAG to fatty acids and glycerol
- fatty acids enter cell
- fatty acids oxidised as fuel or re-esterified to TAG for storage
how are fatty acids released from stored TAG in adipose tissue
- by hormone sensitive lipase (HSL)
- HSL activated by phosphorylation in response to epinephrine
- high plasma glucose and insulin promote desphosphorylation (inactivation) of lipase
how are fatty acids transported in the blood
- free fatty acids transported in complex with serum albumin (plasma protein)
- most fatty acids are esterified and carried in lipoproteins
what do lipoproteins transport
- TAGs
- cholesterol esters
what are the classes of lipoprotein in order of least dense to most dense
- chylomicrons (transport TAG from intestine to tissues)
- VLDL (transports TAG from liver to tissues
- LDL (transports cholesterol to extra hepatic tissues) :(
- HDL (transports cholesterol from tissue to liver for elimination) :)
what is beta oxidation of fatty acids
- occurs in mitochondrial matrix of tissues
- degrades fatty acids two carbons at a time
- produces acetyl coA, NADH and FADH which are sources of energy
what are the three stages of beta oxidation of fatty acids
- activation (of fatty acids in cytosol)
- transport (into the mitochondria)
- degradation (4 stages, degrade two carbons at a time as acetyl coA)
where are fatty acids activated
- cytosol
how are fatty acids transported from cytosol to matrix for beta oxidation
- carnitine shuttle
- fatty acids becomes fatty acyl coA (via phosphorylation by ATP)
- fatty acyl coA diffuses across outer mitochondrial membrane
- coA diffuses across inner mitochondrial membrane and carnitine transports acyl across in the from acyl carnitine
- enzyme on outer mitochondrial membrane is carnitine palmitoyl transferase 1
- enzyme on inner mitochondrial membrane is carnitine palmitoyl transferase 2
what is carnitine palmitoyl transferase inhibited by
- malonyl coA (prevents degradation and synthesis happening simultaneously)
wha happens if you have a carnitine palmitoyl transferase deficiency
- no beta oxidation, hypoglycaemia
- improved with IV glucose
- therapy = give medium chain fatty acids, these do not require the enzyme for transport
what are the four steps of beta oxidation of fatty acids
- dehydration (AKA oxidation) of FAD > FADH2
- hydration (requires H2O)
- dehydration of NAD > NADH
- thiolysis to produce acetyl coA
what is the end result of one round of beta oxidation
- FADH2
- NADH
- acetyl coA
- fatty acids 2 carbon shorter than when it started (2 carbons = acetyl coA)
what is beta oxidation in peroxisome
- very long chain fatty acids >22 carbons undergo preliminary beta oxidation in peroxisomes
- does not produce FADH2 so less energy efficient
- shortened fatty acid linked to carnitine diffuses from peroxisome into mitochondria for further oxidation
why can animals not convert fatty acid into glucose
- due to irreversible step of pyruvate > acetyl coA, via pyruvate dehydrogenase
what inhibits pyruvate dehydrogenase
- acetyl coA
what does pyruvate carboxylase do
- pyruvate > oxaloacetate
- inhibited by acetyl coA
since fatty acid cannot be converted into glucose, how do we get energy when desperately need it and no glucose
- ketone bodies
- fuel molecules
when do you get ketone bodies
- during starvation/fasting, glucose is decreased and excess acetyl coA from fat metabolism can be converted into ketone bodies
- cardiac and skeletal muscle use ketone bodies as energy source
- brain can use ketone bodies during starvation (brain cannot use fatty acid as fuel source)
where are ketone bodies formed
- liver (mitochondrial matrix), liver cannot use them though
- transported with blood to other cells where it is used as fuel, soluble so don’t need to be carried
- ketones: acetone, D-B hydroxybutyrate, acetoacetate)
how do you end up with excess ketone bodies and what happens
- uncontrolled diabetes (or starvation) leads to very high levels of ketone body concentration in blood
- ketonuria (KB in urine)
- ketonaemia (KB in blood)
- academia
- fruity odour to breath due to acetone
- diabetic ketosis results when insulin is absent
where do we get fatty acids from
- diet (essential fatty acids)
- synthesis (from excess carbohydrates, fat and protein components (acetyl coA))
where does FA synthesis occur
- liver (cytosol)
- lactating mammary gland
- (adipose tissue)
what are fatty acids synthesised from
- acetyl coA
- uses NADPH and ATP
why does acetyl coA have to be transferred across the membrane in fatty acid synthesis
- acetyl coA formed in mitochondrial matrix so needs to be transferred to cytosol (site of FA synthesis)
how is acetyl coA transported from the mitochondria to the cytosol for fatty acid synthesis
- citrate shuffle
- occurs when concentration in mitochondria is high
how does the citrate shuffle work
- citrate transfers acetyl coA across the membrane through a protein
- (mitochondria) pyruvate > oxaloacetate > citrate in mitochondria(carries acetyl coA across) > (cytosol) citrate (drops acetyl coA off in cytosol) > oxaloacetate >(NADH used here) malate > (NADPH produced in this reaction) pyruvate (pyruvate goes back across membrane to mitochondria)
what does fatty acid synthesis need
enzymes
- acetyl coA carboxylase (activation/regulation)
- fatty acid synthase (multifunctional enzyme)
needs:
- acetyl coA
- NADPH (P!!!!)
- product is palmitic acid
what is acetyl coA carboxylase (ACC) needed for in fatty acid synthesis
- needed for formation of malonyl coA (activation step)
- ACC is key regulatory enzyme (activated by citrate - signals there is enough glucose so make FA), also activated by insulin
- ACC deactivated by palmitoyl coA (enough FA made so halt synthesis), also deactivated by glucagon and epinephrine
what are the 4 steps in fatty acid synthesis
- elongation (acyl-malonyl ACP condensing enzyme forms acetoacetyl-ACP, ACP=acyl carrier protein)
- reduction
- dehydration
- reduction
- elongation cycle is repeated 6x more using malonyl coA each time to produce palmityl ACP
- a thioesterase then cleaves the palmityl-coA from the ACP (acyl carrier protein)
what is multifunctional fatty acid synthase
- complex of 7 enzymes
- has role in fatty acid synthesis
what is the fate of fatty acid
in order
- acetyl coA
- (liver) fatty acid
- TAG
- VLDL
- adipose tissue
does fatty acid degradation and synthesis run at the same time
- no
what are steroids
- major class of lipids
- contain ring system
what are the three classes of steroids
- cholesterol (starting material for the synthesis of bile salts, steroid hormones and other components)
- steroid hormones (chemical messengers e.g. corticosteroids)
- bile salts (sodium salts of steroids used for emulsification)
what is cholesterols
- class of steroid
- component of cell membranes
- precursor to other substances (steroid hormones, vitamin D, bile acids)
where is cholesterol made
- mainly in liver
- only found in food substances e.g. milk, meat
what are statins
- inhibit HMG-CoA reductase that is essential in cholesterol synthesis
- lowers LDL levels
- lowers risk of cardiovascular disease
what are Eicosanoids
- lipid class derived from 20 carbon unsaturated fatty acids and synthesised throughout body
- signalling molecule derived from omega 3 or 6 fatty acids
- precursors to prostaglandins, thromboxanes and leukotrienes
- short half life (metabolised rapidly), produced and act locally
what do Eicosanoids regulate
- inflammatory response
- pain and fever (prostaglandins)
- blood clotting induction/platelet homeostasis (thromboxane)
- blood pressure regulation (prostacyclin)
- many reproductive functions (e.g. labour induction, menstrual cramps, sperm mobility - prostaglandins)
- smooth muscle construction and bronchoconstriction (leukotrienes)
- mucous production in stomach (prostaglandins)
