lipid metabolism Flashcards
structure of lipids (triacylglycerols)
glycerol
3 fatty acids
linked by ester bonds
how is energy obtained from lipids?
lipids broken down into glycerol and fatty acids
- in cytoplasm
fatty acids activated into fatty acetyl CoAs
- transported into mitochondria
beta oxidation produces acetyl CoA, FADH2 and NADH
- in the mitochondria
describe lipolysis
breakdown of triacylglycerol into glycerol and 3 fatty acids
series of 3 hydrolysis reactions
one fatty acid released by each
uses water
enzymes used in lipolysis
triacylglycerol lipase
diacylglycerol lipase
monoaceylglycerol lipase
tri - di - mono - glycerol and fatty acids
products of lipolysis
forms glycerol and 3 fatty acids
glycerol can be used to generate energy
converted to dihydroxyacetone phosphate
- substrate for gluconeogenesis
- energy through glycolysis, link and TCA
activation of fatty acids
fatty acids converted to fatty-acyl CoA
(substrate for beta oxidation)
catalysed by fatty acyl CoA synthesise
occurs in cytoplasm
- but need to be moved to mitochondria
activation of one requires 2 ATP
2 phosphates released and AMP produced from ATP synthesis
why do fatty acyl CoAs need a transport system? (beta oxidation)
transported from cytoplasm to mitochondria
cannot move directly as inner membrane has limited permeability
polar molecule
use transport system involving carnitine as the carrier
3 proteins needed:
- carnitine-acyltransferase 1 (CAT 1)
- carnitine-acyltransferase 2 (CAT 2)
- transfer protein
transport of fatty acyl CoAs
CAT 1 removes CoA from fatty acyl CoA
replaced with carnitine
forms fatty acyl-carnitine
transfer proteins moves fatty acyl-carnitine into matrix
CAT 2 removes carnitine
replaced with new CoA from matrix
remakes natty acyl CoA
carnitine moved from matrix to inter membrane space through transfer proteins
used again
beta oxidation of fatty acids
beta carbon is oxidised (3)
each cycle shortens fatty acyl CoA chain by 2 carbons
repeated cycle of 4 reactions:
oxidation
hydration
oxidation
cleavage
takes place until fatty acyl CoA fully oxidised
each 4 produces
acetyl CoA
FADH, NADH
beta oxidation - oxidation 1
fatty acyl CoA converted to trans-Enoyl CoA
catalysed by fatty acyl CoA dehydrogenase
two hydrogen atoms removed
- one from alpha (2) and 1 from beta (3) in hydrocarbon chain
FAD reduced and acts as hydrogen carrier
1 molecule of FADH per 1 FA CoA
FADH oxidised via ETC to produce 2 ATP in oxidative phosphorylation
beta oxidation - hydration
trans-Enoyl CoA hydrated to L-3-hydroxyl acyl CoA
catalysed by enoyl CoA hydrase
hydrogen added to alpha
hydroxyl (OH) added to beta from water
beta oxidation - oxidation 2
L-3-hydroxyl acyl CoA dehydrogenated to 3-keto acyl CoA
catalysed by 3-hydroxyl acyl-CoA dehydrogenase
two hydrogen removed from beta
1 NAD reduced per molecule
- goes through ETC = 3 ATP per NADH in oxidative phosphorylation
keto group introduced to beta carbon
beta oxidation - cleavage
3-keto acyl CoA converted to fatty acyl CoA and acetyl CoA
catalysed by 3-keto acyl CoA thiolase
removes 2 carbon unit from keto molecule in form of acetyl CoA (2C removed)
replaced with new CoA
means chain shortened by 2 carbons
re-enter in new cycle
produces 1 acetyl CoA molecule - enters TCA cycle = 12 ATP per molecule
new fatty acyl CoA - 2C shorter
what is the malonyl pathway?
how fatty acids are synthesised
acetyl CoA (2C) converted to malonyl CoA (3C)
occurs in cytoplasm
requires
- CO2
- co-factors (biotin)
- reducing power (NADPH)
repeated cycle of 4 reactions
extends chain by 2 carbons each time
why is a transport system needed for acetyl CoA? (malonyl)
transported from matrix to cytoplasm
carotene better for transporting longer chain fatty acetyl CoAs
but only a 2 carbon molecule
transport of acetyl CoA (tricarboxylate transport system)
inside mitochondria:
acetyl CoA condenses with oxaloacetate = citrate
catalysed by citrate synthase
citrate transported into cytoplasm by citrate carrier protein
in cytoplasm:
citrate cleaved to oxaloacetate and acetyl CoA
catalysed by ATP-citrate lyase
acetyl CoA now used for fatty acid synthesis
carboxylation of acetyl CoA to malonyl CoA
catalysed by acetyl CoA carboxylase
irreversible
requires carbon from CO2, biotin and 1 ATP
biotin covalently attached to ACC
carboxyl group transferred to biotin
= ACC-biotin-COO- + ADP + Pi
carboxyl group transferred from biotin to acetyl CoA
acetyl CoA + carboxyl = malonyl CoA
activation of fatty acids in malonyl
1 acetyl and 1 malonyl activated
bind to an acyl carrier protein (ACP)
2 binding sites:
malonyl to site 1
acetyl to site 2
activation of acetyl CoA (malonyl)
converted to acetyl-ACP
binds to site 2
facilitated by acetyl transferase
CoA removed
acetyl attached to ACP
activation of malonyl CoA (malonyl)
converted to malonyl-ACP
binds to site 1
facilitated by malonyl transferase
CoA removed
acetyl attached to ACP
outline of malonyl pathway
repeated cycle of 4 reactions
condensation
reduction
dehydration
reduction
cofactors used as reductant during reduction reactions
NADPH becomes oxidised as substrates reduced
fatty acid chain extended by 2 carbons in each cycle
how is fatty acid synthesis (malonyl) catalysed?
fatty acid synthase
prokaryotes
FAS = protein complex of distinct enzymes
contains all enzymes required
eukaryotes
FAS is a single protein
multiple active sites
each catalyses a different reaction
malonyl pathway - condensation
acetyl CoA nad malonyl CoA form 3 ketoacyl ACP
catalysed by condensing enzyme
malonyl looses the carbon from CO2
carbon replaced by acetyl group of acetyl ACP
all carbon atoms originate from acetyl ACP
CO2 and ACP released
malonyl pathway - reduction 1
3 ketoacyl ACP reduced to 3 hydroxyl ACP
catalysed by 3 ketoacyl ACP reductase
3 ketoacyl molecules recued
uses NADPH as H donor - oxidised to NADP
beta carbon accepts both H atoms
malonyl pathway - dehydration
3 hydroxyl dehydrated to trans enoyl ACP
catalysed by 3-hydroxyacyl ACP dehydratase
water removed
hydroxyl (OH) removed from beta carbon
H removed from alpha carbon
malonyl pathway - reduction 2
trans enoyl reduced to fatty acyl ACP
catalysed by enoyl ACP reductase
used 1 NADPH as H donor - becomes oxidised to NADP
hydrogen atoms added to beta and alpha carbons
forms fatty acyl ACP 2 carbon longer
products of 1 round of malonyl pathway
uses 1 malonyl ACP
1 acetyl ACP
2 NADPH (NADP produced)
produces fatty acyl ACP 2 carbons longer
on site 1 of ACP
what must happen before a second cycle of the malonyl pathway can begin?
fatty acyl transferred from site 1 to site 2 of ACP
catalysed by acetyl transferase
new malonyl group attached to site 1
catalysed by malonyl transferase
what happens when a 16 carbon fatty acyl ACP is produced?
after 7 rounds
thioesterase removes and releases a 16 carbon fatty acid from site 1 of ACP
both site 1 and 2 now free so new malonyl and acetyl can be activated
