biochem lecture 8 pt 2 Flashcards
what have we already done in step 1
we get fatty acids mobilized and transported, absorbed into muscle cell
what is step 2 in beta oxidation
activation of fatty acids, and transportation to mitochondria for degradation
what happens when fatty acids are absorbed into muscle cell
need to undergo an activation step in the cell
what happens once those fatty acids have been activated
need to be transported into mitochondrial matrix
what happens to individual fatty acids in step 2
transported into muscle cell and converted into a fatty acyl CoA
what is coenzyme A
important metabolic tag
what does being tagged w/ coenzyme A mean
compound is biochemically activated in some way; gonna go into a specific metabolic pathway
what is carnitine
molecule needed for the import of fatty acyl CoAs into mitochondria
what do we need to do to fatty acyl CoA
convert fatty acyl CoA –> fatty acyl carnitine
why do we need to go through this interconversion from fatty acyl CoA to fatty acyl carnitine
because there is a specific transporter that will recognize fatty acyl carnitine and bring it into mitochondrial matrix
what happens once fatty acyl carnitines brought into mitochondrial matrix
they are interconverted back into fatty acyl CoAs, where they go thru beta-oxidation
what happens when fatty acyl CoAs are in mitochondria
go through beta oxidation pathway
what happens to carnitine released from this step
transported out of mitochondria, brings more fatty acids into mitochondria
what is the overall rxn in activation step
take fatty acid that’s been brought into cell, and produce fatty acyl CoA
describe thermodynamics of activation step
large negative delta G; exergonic
why is it exergonoic
cuz we couple it to hydrolysis of ATP
what enzyme for activation step
fatty-acyl CoA synthetase
what happens in activation step
fatty acid –> fatty acyl adenylate intermediate (by fatty-acyl coa synthetase)
what happens after fatty acyl adenylate intermediate
fatty acyl CoA adenylate –> fatty acyl CoA (by fatty-acyl coa synthetase)
basically what happens in activation step
fatty acid –> fatty acyl CoA adenylate –> fatty acyl CoA (from 2 rounds of fatty acyl CoA synthetase)
how do we form this thioester bond
pyrophosphate leaving group is released, and this generates formation of thioester bond in fatty acyl CoA
why exergonic
ATP hydrolyzed; intermediate has a phosphate group from ATP attached
where does generation of fatty acyl CoAs occur
in cytoplasm of muscle cell
what happens once we have fatty acyl CoAs
we have to get fatty acyl units to mitochondrial matrix
how do we get fatty acyl CoA to mitochondria
set of interconversion reactions where we swap coenzyme A for carnitine
what enzymes are involved
2 acetyl transferases: carnitine acetyl transferase I, carnitine acetyltransferase II
what is CAT 1
resides in outer membrane
what is CAT II
in inner mitochondrial membrane
what is Cat 2 important for
for when we convert fatty acyl carnitine back into fatty acyl coenzyme A
describe transportation step
formation of catty acyl carnitine from fatty acyl CoA. CAT I transfers fatty acyl carnitine to intermembrane space. CAT II is waiting for fatty acyl carnitine in mitochondrial matrix, and will do the second interconversion reaction
what is end product after step 2
we end up w/ a fatty acyl CoA which goes through beta oxidation pathway
how many stages in beta oxidation
3;
stage 1 of beta oxidation
B-oxidation of fatty acids
stage 2 of beta oxidation
acetyl CoA oxidized to Co2
what is stage 3 of b-oxidation
electrons transferred from NADH/FADH2 to ETC for electron synthesis
what do we do in beta oxidation
we are removing 2 Cs at a time off fatty acid, with each round
but in all situations what do we have culmination of
culmination of beta oxidation of fats
what happens if we have double bonds (one or more)
its about getting rid of those double bonds to generate a fully saturated fatty acid
what happens once we have saturated fatty acid
can be sent thru beta oxidation pathway
what’s the point of beta oxidation pathway
generates acetyl CoA units, which can be fed into TCA cycle
what do fats generate a lot of
generate a lot of reducing power (NADH, FADH) in TCA cycle
where does that reducing power go
fed into ETC, important for ox phos
what are the 4 scenarios of beta oxidation
even & saturated, even & monounsaturated, even & polyunsaturated, odd
what’s the simplest case
even & saturated
what 4 steps
oxidation, hydration, oxidation, thiolysis
where is 1st step
fatty acyl CoA (starting point), we are in mitochondrial matrix
describe 1st step
fatty acyl CoA oxidized to trans delta 2 enoyl CoA
what kinda rxn is 1st step
oxidation rxn
what else is produced in 1st oxidation
FADH2
why is trans delta 2 enoyl CoA important
because in other pathways, it all boils down to getting to this intermediate
2nd step
trans delta 2 enoyl CoA –> 3-hydroxyacyl CoA intermediate
what kinda rxn in step 2
hydration step; input of water
step 3
second oxidation step, results in another reducing power molecule created
describe step 3
3-hydroxyacyl CoA –> 3-ketoacyl CoA intermediate
what else is produced in step 3
reduction of NAD+ to NADH, simultaneous oxidataoin
step 4
2 products: acyl CoA and acetyl CoA; we keep converting acyl CoA to acetyl CoA until we’re done
what extra enzyme in even monounsaturated enzyme
enoyl-CoA isomerase
how much ATP per double bond does enoyl CoA isomerase use
2 ATP
what enzymes does even polyunsaturated fatty acids use
enoyl CoA isomerase AND 2,4-dienoyl CoA reductase
how much ATP per double bond in 2,4-dienoyl CoA reductase
3 ATP
B-oxidation in odd fatty acids
keep doing beta oxidation until you reach 3Cs
what happens to those remaining 3 Cs
succinyl CoA
where does succinyl CoA go
into TCA
describe b-oxidation for odd stuff
propionyl CoA –> methylmalonyl CoA –> methylmalonyl CoA –> succinyl CoA
what 3 enzymes
propionyl CoA carboxylase, methylmalonyl CoA epimerase, methylmalonyl CoA mutase
what undergoes lipgenesis
excess dietary glycerol and fatty acids undergo lipogenesis to make triglycerides
why is glucose easily converted to fat
acetyl CoA is intermediate in glucose metabolism and starting molecule for fatty acid synthesis
what does release of insulin favor
lipogenesis to form triglycerides
what else are fats derived from besides excess dietary lipids
glucose
liypolysis
breakdown of stored fat
what is lipolysis reverse of
reverse of lipogenesis
what is necessary for complete oxidation of fat (thru TCA cycle)
oxaloacetete
what would happen to acetyl CoA without oxaloacetate
ketogenesis; acetyl CoA converted into ketones
when does ketogenesis occur
long term starvation conditions; decline in oxaloacetate levels
where does ketogenesis happen
in liver
ketone bodies
utilized as a way to generate fatty acids (fatty acid –> beta oxidation –> ATP)
what else can ketone bodies be converted into
acetyl CoA
what happens w/ ketone bodies in long term starvation conditions
ketone bodies –> acetyl CoA –> into TCA cycle to keep it going
what do we see in intermediate to longer term starvation conditions
ketogenesis
what’s the main idea w ketone bodies
ketone bodies generated from ketogenesis in liver are used to make acetyl CoA –> goes into TCA cycle, generates reducing power to make ATP in starvation conditions
basically what is ketogenesis
kind of diverting certain carbon skeletons that can be utilized in longer term starvation conditions
what are anabolic and catabolic pathways of lipids reciprocally regulated by
insulin and glucagon
when is oxidation of fats unecessary
when diet provides carbohydrate fuel
what 2 enzymes for coordinated regulation
acetyl-CoA carboxylase (ACC), carnitine acyl transferase I (CAT I)
what is ACC
first enzyme in fatty acid synthesis pathway
what does ACC do
takes acetyl CoA, feeds it to biosynthesis pathway for fatty acids
what is CAT I important for
uptake/transport of fatty acids in mitochondrial matrix where b-oxidation occurs
what does insulin promote
uptake, synthesis, storage of triglycerides
what does glucagon promote
degradation/breakdown of triglycerides
when is insulin released
high blood glucose conditions
when is glucagon released
low blood glucose conditions
what kinase mediates these effects
PKA
what does glucagon do
stimulates PKA
what does insulin
activates PP1
what is first intermediate of fatty acid biosynthesis
malonyl CoA
what does ACC do
acetyl CoA –> malonyl CoA
what is used in synthesis of fatty acid from here
malonyl CoA
what happens in low blood glucose conditoins
glucagon –> activates PKA –> phosphorylates & inhibits ACC
what does low blood glucose do to ACC
inhibits ACC
what does inhibiting ACC do
lowers malonyl CoA (first intermediate in the pathway)
what does malonyl CoA do (besides being intermediate in fatty acid synthesis)
allosteric regulator of CAT I
what does high malonyl CoA levels mean
inhibit CAT I
what happens if we inhibit CAT I
we inhibit the conversion of fatty acyl CoA to fatty acyl Carnitine, and uptake of fatty acyl units into mitochondria
basically what does inhibition of CAT I do
prevents beta oxidation (not enough fatty acyl groups feeding into b-oxidation pathway)
so describe effects of low blood glucose
glucagon –> inhibits ACC –> inhibits first step of biosynthesis pathway (malonyl CoA) –> increases CAT I activity –> favors uptake and oxidation of fatty acids
why does blood glucose condition favor uptake and oxidation of fatty acids
low blood glucose means E levels are low, and we need to use fats as an E source (since glycogen stores depleted we can’t use that as E source)
describe low blood glucose/glucagon pathway
Low blood glucose conditions → glucagon → PKA → phosphorylates and inhibits ACC → lower levels of malonyl CoA (allosteric regulator of CAT I) → higher levels of CAT I, together w/ presence of fatty acyl coAs → conversion into fatty acyl carnitines → import into mitochondrial matrix → fatty acids undergo oxidation (E source)
describe high blood glucose conditions
insulin –> stimulates PP1 –> stimulates ACC (dephosphorylates it)
what does dephosphorylating ACC do
favors its activation
what does activating ACC do
increases malonyl CoA
what does increasing malonyl CoA do
inhibits CAT I
what does inhibiting CAT I do
inhibits beta oxidation
describe high blood glucose / insulin pathway
high blood glucose conditions → insulin → PP1 → dephosphorylates and activates ACC → higher levels of malonyl CoA (allosteric regulator of CAT I) → inhibits CAT I, inhibits beta oxidation
basically what does glucagon/low blood glucose do
inhibits ACC; favors beta oxidation vs. fatty acid synthesis; keeps malonyl CoA levels low
basically what does insulin/high blood glucose do
favors fatty acid synthesis by stimulating PP1, activating ACC, higher levels of malonyl CoA, inhibits CAT I and thus beta oxidation
what does a high carb meal do
stimulates insulin release
what happens in high carb meal
PP1 dephosphorylates and activates ACC, ACC increases malonyl CoA, inhibiting CAT I
what happens when blood glucose drops between meals
glucagon activates PKA, phosphorylates & inhibits ACC, lowers malonyl CoA, increases CAT I, stimulates FA oxidation
