lipid metabolism Flashcards

1
Q

structure of lipids (triacylglycerols)

A

glycerol
3 fatty acids
linked by ester bonds

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2
Q

how is energy obtained from lipids?

A

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

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3
Q

describe lipolysis

A

breakdown of triacylglycerol into glycerol and 3 fatty acids

series of 3 hydrolysis reactions
one fatty acid released by each
uses water

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4
Q

enzymes used in lipolysis

A

triacylglycerol lipase
diacylglycerol lipase
monoaceylglycerol lipase

tri - di - mono - glycerol and fatty acids

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5
Q

products of lipolysis

A

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

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6
Q

activation of fatty acids

A

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

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7
Q

why do fatty acyl CoAs need a transport system? (beta oxidation)

A

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

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8
Q

transport of fatty acyl CoAs

A

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

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9
Q

beta oxidation of fatty acids

A

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

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10
Q

beta oxidation - oxidation 1

A

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

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11
Q

beta oxidation - hydration

A

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

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12
Q

beta oxidation - oxidation 2

A

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

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13
Q

beta oxidation - cleavage

A

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

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14
Q

what is the malonyl pathway?

A

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

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15
Q

why is a transport system needed for acetyl CoA? (malonyl)

A

transported from matrix to cytoplasm
carotene better for transporting longer chain fatty acetyl CoAs
but only a 2 carbon molecule

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16
Q

transport of acetyl CoA (tricarboxylate transport system)

A

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

17
Q

carboxylation of acetyl CoA to malonyl CoA

A

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

18
Q

activation of fatty acids in malonyl

A

1 acetyl and 1 malonyl activated

bind to an acyl carrier protein (ACP)
2 binding sites:
malonyl to site 1
acetyl to site 2

19
Q

activation of acetyl CoA (malonyl)

A

converted to acetyl-ACP
binds to site 2

facilitated by acetyl transferase
CoA removed
acetyl attached to ACP

20
Q

activation of malonyl CoA (malonyl)

A

converted to malonyl-ACP
binds to site 1

facilitated by malonyl transferase
CoA removed
acetyl attached to ACP

21
Q

outline of malonyl pathway

A

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

22
Q

how is fatty acid synthesis (malonyl) catalysed?

A

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

23
Q

malonyl pathway - condensation

A

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

24
Q

malonyl pathway - reduction 1

A

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

25
Q

malonyl pathway - dehydration

A

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

26
Q

malonyl pathway - reduction 2

A

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

27
Q

products of 1 round of malonyl pathway

A

uses 1 malonyl ACP
1 acetyl ACP
2 NADPH (NADP produced)

produces fatty acyl ACP 2 carbons longer
on site 1 of ACP

28
Q

what must happen before a second cycle of the malonyl pathway can begin?

A

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

29
Q

what happens when a 16 carbon fatty acyl ACP is produced?

A

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