8. fatty acid metabolism and ketone bodies Flashcards
Lipids:% in body weight
storage and structural
19%
storage: triacylglycerols in adipose
structural: phospholipids
structure of fatty acids
- Hydrophobic hydrocarbon chain and hydrophilic carboxyl group
- Saturated: no double bonds in the alkyl chain
Unsaturated: one or more double bonds
•Cis and trans configuration around double bonds
trans fatty acids
- Formed by hydrogenation of vegetable oils to form margarines
- Widely used in snacks, biscuits
- Associated with greater risk of coronary heart disease
properties of fatty acids
•Hydrophobic tail and hydrophilic head
–amphipathic, act like detergents
•Lipids containing saturated fatty acids often solids at room temperature
–eg. animal fats (butter, lard etc)
•Lipids containing unsaturated fatty acids tend to be liquid at room temperature
–eg. vegetable oils, olive oil
•Animal fat 40-60% saturated, little PUFA, plant oils 80-90% unsaturated
triacylglycerol
•Fatty acids stored in adipose tissue esterified to glycerol
–Ester linkage between fatty acid carboxyl and glycerol hydroxyl group
•3 fatty acids esterified forms triacylglycerol
–is highly reduced, high calorific value
–is virtually anhydrous, (vs glycogen) and pack closely together without much water
which tissues can undergo fatty acid oxidation
liver and muscle, not brain and RBC
mobilisation of fatty acids:
what do hormones activate?
how are FFA released to plasma
- Glucagon (starvation) or adrenaline (stress), corticol activate a hormone-sensitive lipase which hydrolyses triacyglycerol in adipose tissue to free fatty acids and glycerol
- Free fatty acids are released to the circulation bound to plasma albumin
- Fatty acids released to target tissues, cross into cytosol of cell to liver/ muscles
transport of FFA from adipose to be oxidised in skm
Fate of glycerol and fatty acids
•Glycerol:
–Transported to liver, phosphorylated to glycerol 3-phosphate and converted to dihydroxyacetone phosphate (DHAP)
–DHAP used in glycolysis or gluconeogenesis
•Fatty acids:
–Taken up by tissues – freely cross membrane
–Converted to acetate units by b-oxidation
b-Oxidation of fatty acids
•Long chain fatty acids are first activated in the cytosol to form thiol esters with coenzyme A (CoA)
–Consumes ATP
- LCFAs then imported into mitochondria for b-oxidation
- b-oxidation generates NADH, FADH2 and acetylCoA
Import of LCFAs into mitochondria
- CoA esters cannot cross mitochondrial inner membrane
- Long chain fatty acyl group transferred to carnitine
- LC Fatty acyl carnitine transported into mitochondrial matrix – carnitine exported (shuttle)
- LC fatty acyl group transferred to CoA
- Short and medium chain fatty acids pass directly into mitochondria where they are activated to fatty acylCoAs
carnitine
where is it obtained
where is it synthesised
what can deficiency lead to
- Obtained from meat in diet
- Synthesised in liver and kidney, supplied to muscles by kidney via blood
- Carnitine deficiency (liver disease, malnutrition, trauma, pregnancy or congenital deficiency) can lead to build up of toxic LCFAs – neurological damage, cannot metabolise FFA, not enough ATP compromises pathways
b-Oxidation of fatty acids
mechanism
•Fatty acyl groups subjected to repeated rounds of:
–Oxidation – generates double bond on C2 (trans) and FADH2
–Hydration – generates OH on C3 (b carbon)
–Oxidation – generates carbonyl on C3 and NADH
–Thiolytic cleavage – generates acetylCoA and shortened fatty (- 2C) acylCoA
Energy yield starting with C16 saturated fatty acid (palmitate) from b-oxidation
7 FADH2 = 14 ATP
7 NADH = 21 ATP
8 acetylCoA = 96 ATP (via TCA cycle)
Formation of LC fatty acylCoA = equivalent of 2 ATP
Net yield = 131-2 = 129 ATP
Compare to glucose (2 ATP via anaerobic glycolysis, 36 ATP via ETC)
Regulation of b-oxidation
- supply of substrate so depends on rate of lipolysis in adipocytes, - regulated by hormones
- Malonyl CoA inhibits CPTI (uptake of LCFA into mitochondria). fatty acid synthesis and b-oxidation are reciprocally regulated.
- Note: fatty acids cannot be converted to glucose (the glycerol from triacylglycerol can, minor contribution to gluconeogenesis)
what does this show us
that Fatty acid oxidation & fatty acid synthesis are linked reciprocally
where does ketone body synth occur?
what are the ketone bodies formed?
what are the fates of these bodies?
- In mitochondria of liver
- Two ketone bodies formed - acetoacetate and b-hydroxybutyrate
–Acetone is also formed but cannot be utilised, excreted on breath producing typical smell on the breath of a ketotic individual
•Acetoacetate reduced to b-hydroxybutyrate when NADH high
–High NADH in liver when b-oxidation active (starvation)
