Energy production - Lipids Flashcards
lipids
- structurally diverse
- generally insoluble in water (hydrophobic)
- soluble in organic solvents
- contain C, H, O (phospholipids contain P, N)
- more reduced than carbohydrates so release more energy when oxidised
3 classes of lipids
fatty acid derivatives
- fatty acids - fuel molecules
- triacylglycerols - fuel storage and insulation
- phospholipids - membrnaes + lipoproteins
- eicosanoids - local mediators
hydroxy-methyl-glutaric acid derivatives
- ketone bodies (C6) - water soluble fuel molecules
- cholesterol (C27) - membranes + steroid hormones
- cholesterol esters - cholesterol storage
- bile acids and salts (C24) - lipid digestion
vitamins
- A
- D
- E
- K
triacylglycerols
- major dietary and storage lipid
- three fatty acids esterified to glycerol
- hydrophobic
- stored in anhydrous form
- stored in highly specialised storage tissue - adipose
- used in prolonged aerobic exercise, starvation, pregnancy
- storage/mobilisation under hormonal control
hormonal control of storage of triacylglycerols
promoted by
- insulin
reduced by
- glucagon
- adrenaline
- cortisol
- growth hormone
- thyroxine
stage 1 metabolism of triacylglycerols
- hydrolysed by pancreatic lipase in the small intestine to release glycerol and fatty acids
- requires bile salts and protein factor called colipase
fatty acids
- hydrophobic
- highly reduced molecules
- saturated or unsaturated
- ideal for energy storage
fatty acid catabolism
- FA activated by linking to coenzyme A outside mitochondrion
- transported across innner mitochondrial membrane using carnitine shuttle
- FA cycles through sequences of oxidative reactions with C2 removed each time
why does β oxidation not occur in cells of central nervous system
fatty acids do not readily cross the blood-brain barrier
lipolysis
- adipose tissue triacylglycerols hydrolysed by hormone-sensitive lipase
- fatty acids and glycerol diffuse from tissue
- when body subjected to stress situations
- activated by adrenaline, glucagon, growth hormone, cortisol and thyroxine
- inhibited by insulin
how are fatty acids transported
carried to tissues via blood stream bound non-covalently to albumin (called NEFA or FFA)
what happens to glycerol
- transported in blood to liver
- converted to glycerol phosphate by glycerol kinase and ATP
- used to synthesise triacylglycerols or enters glycolysis
- enters glycolysis by being converted to dihydroxyacetone phosphate (DHAP) by glycerol 3-phosphate dehydrogenase and NAD+
fatty acid activation
- outside mitochondria, in cytoplasm
- fatty acids link to coenzyme A by action of fatty acyl CoA synthase and ATP
- forms high energy hydrolysis bond via the S-atom
- CoA contains vitamin B5 and free -SH group
- activated fatty acids do not readily cross inner mitochondrial membrane
fatty acid transport into mitochondria
- carnitine shuttles exchange acyl carnitine for free carnitine using CAT 1/2 (carnitine acyltransferases) to transport fatty acyls across mitochondrial membrane which rejoin with CoA in matrix
- important in regulating rate of FA oxidation
- regulated by AMP and insulin
- CAT1 inhibited by malonyl CoA, prevents newly synthesised fatty acids being immediately transported into mitochondria
- defective transport system = poor exercise tolerance, lipid droplets in muscle cells
β oxidation of fatty acids
- generates acetyl CoA and reducing power (NADH and FADH2)
- fatty acid is oxidised and **C2 unit (acetate) is removed **
- shortened fatty acid is cycled, repeatedly removing C2 until 2 carbons remain
- requires mitochondrial NAD+, FAD+ and oxygen (re-oxidise NADH and FADH2)
acetyl CoA
- produced by catabolism of fatty acids, sugars, alcohol and amino acids
- oxidised via stage 3 catabolism (Kreb’s cycle)
- important intermediate in lipid biosynthesis
what are the 3 ketone bodies produced in the body
- acetoacetate (in liver from acetyl Co-A)
- β-hydroxybutyrate (in liver from acetyl Co-A)
- acetone (spontaneous decarboxylation of acetoacetate)
plasma concentrations of ketone bodies
- normal <1mmol/L
- starvation 2-10mmol/L (physiological ketosis)
- untreated type 1 diabetes >10mmol/L (pathological ketosis)
ketonuria
excretion of ketone bodies in urine
properties of ketone bodies
- water-soluble - allows high plasma concentrations and ketonuria
- high concentrations of acetoacetate and β-hydroxybtyrate cause ketoacidosis
- acetone is volatile and excreted through lungs (smell of acetone on breath of untreated type 1 diabetics)
where are ketone bodies synthesised
liver mitochondria by actions of lyase and reductase enzymes that are reciprocally controlled by insulin/glucagon ratio
ketone body synthesis pathway
- acetyl Co-A
- HMG-CoA (synthase)
- acetoacetate (lyase)
- β-hydroxybutyrate or acetone
how do statins reduce cholesterol
they act as HMG-CoA reductase inhibitors so cholesterol can’t be formed from acetyl Co-A
ketone body synthesis when insulin/glucagon ratio is high (fed)
- lyase inhibited
- reductase activated
- cholesterol synthesis occurs
ketone body synthesis when insulin/glucagon ratio is low (starvation)
- lyase activated
- reductase inhibited
- ketone body synthesis occurs (ketogenesis)
2 things the synthesis of ketone bodies requires
- availability of fatty acids from excess lipolysis in adipose tissue to provide substrate by oxidation in the liver (excess acetyl Co-A)
- low plasma insulin/glucagon ratio to activate lyase and inhibit reductase
control of ketone body production in liver
- high levels of triacylglycerols so conversion to acetyl Co-A uses up NAD+
- low NAD+ inhibits TCA cycle (isocitrate dehydrogenase and α-ketoglutarate dehydrogenase)
- acetyl Co-A diverted from TCA cycle to ketogenesis
why are ketone bodies produced
- important fuel molecules that can be used by all tissues containing mitochondria including the CNS
- alternative fuel to glucose so way of conserving glucose in starvation/diabetes
metabolism of ketone bodies
- synthesised in the liver
- transported in blood
- acetone excreted through lungs
- acetoacetate and β-hydroxybutyrate converted back to acetyl Co-A in muscle
- acetyl Co-A enters TCA cycle
amphipathic fatty acids
contain hydrophobic and hydrophilic groups
