lipid degradation: beta oxidation Flashcards
beta oxidation converts ____ into ____
palmitoyl-CoA into acetyl-CoA
what is the name of first step of beta oxidation
dehydrogenation
describe the first step of b-ox
acyl-CoA dehydrogenases catalyze the formation of a trans double bond between a and b carbons. FAD gets reduced to FADH2
which enzyme catalyzes the first step of b-ox
acyl-CoA dehydrogenase
what are the by-products of step 1 of b-ox
FADH2
name step 2 of b-ox
hydration
describe step 2 of b-ox
water is added to the trans double bond of the a and b carbons = a single bond and an OH on the b carbon
name step 3 of b-ox
dehydrogenation #2
describe step 3 of b-ox
another dehydrogenation occurs = a ketone on the b carbon. NAD+ is reduced to NADH
what is the by-product of step 3 of b-ox
NADH
name step 4 of b-ox
thiolysis
describe step 4 of b-ox
thiolysis of the two carboxy-terminal carbons via a free molecule of CoA (cleavage between carbons a-b)
what is the end result of the first 4 steps (1 round) of b-ox
14C-CoA, acetyl-CoA
how many rounds of b-ox are needed to complete the cleavage of palmitate/palmitoyl-CoA
7
how many acetyl-CoA molecules are we left with after 7 rounds of b-ox
8 acetyl CoA
after 7 rounds of b-ox, why are we left with 8 acetyl-CoA and not 7
each round produces 1 acetyl-CoA, but the last round will produce 2 (when the 4C molecule is cleaved)
after 7 rounds of b-ox, how many FADH2 do we have
7
after 7 rounds of b-ox, how many NADH do we have
7
after 7 rounds of b-ox, how many H+ do we have
7
after b-ox, where do FADH2 and NADH go
to the ETC to drop off electrons to O2
each FADH2 produces ___ molecules of ATP in the ETC
1.5
each NADH produces ___ molecules of ATP in the ETC
2.5
each pair of electrons donated to O2 in the ETC produce ___ H2O molecule(s)
1
how many ATP are produced during ONE round of b-ox. Explain (assuming NADH and FADH2 went to the ETC)
4 ATP: each round produces 1 FADH2 and 1 NADH. FADH2 produces 1.5 ATP in the ETC and NADH produces 2.5 ATP in the ETC. 1.5 + 2.5 = 4 ATP produced
how many H2O are produced during ONE round of b-ox. Explain (assuming NADH and FADH2 went to the ETC)
2 H2O: one electron pair = 1 water. Each round of b-ox produces 2 electron pairs
how many H2O were USED during one round of b-ox
1 H2O used per round
what is the net amount of water produced by all 7 rounds of b-ox? explain
7 H2O produced (net). 14 were produced via electrons being donated to O2, but 7 were used in the dehydration step
how much ATP was formed after all 7 steps of b-ox, ONLY FROM reduced electron carriers
1 round = 4 ATP (1.5 +2.5=4), but there were 7 rounds
4x7 = 28 ATP produced from b-ox
After b-ox, where do the 8 acetyl-CoA molecules go?
they go to the CAC
what is the result of the acetyl-CoA from b-ox going to the CAC
more ATP will be produced!
each turn of the CAC produces __ NADH
3
each turn of the CAC produces __ FADH2
1
each turn of the CAC produces __ CO2
2
each turn of the CAC produces __ ATP equivalent (GTP)
1
how many rounds of CAC (and subsequent ETC) need to occur
8 (because there are 8 acetyl-CoA’s)
after 8 rounds of the CAC (and subsequent ETC), how many ATP are produced? explain
80
- (3 NADH x 2.5)+ (1 FADH2 x 1.5) = 9 ATP
- 1 ATP equivalent produced in the CAC
- 9 + 1 = 10 ATP
- 8 rounds: 8 x 10 = 80 ATP total
combining the numbers from complete b-ox and CAC and ETC, how many ATP do we get
108 (28 + 80)
where does b-ox occur in the cell
mitochondria matrix
what was the cost of ATP to add CoA to the FA to activate it in preparation for entry to the mito matrix (carnitine shuttle, prior to b-ox)
2 ATP needed
when considering the cost of 2 ATP needed PRIOR to b-ox, what is the NET ATP number (b-ox, CAC, ETC)
106 ATP
what is the issue with trying to oxidize an unsaturated FA
the enzyme for step 1 can only act on trans double bonds at C2, and natural FA bonds are cis, so the enzyme may not work on an unsat FA
what two enzymes do we need to oxidize an unsat FA
isomerase and reductase
explain how we oxidize MUFAs (ie oleate)
first 3 rounds happen without issue, but at round 4 there will be a cis (we don’t want) at C3 (wrong spot). isomerase converts the natural cis bond to a trans at C2 which fixes the issue
explain how we oxidize PUFAs (ie linoleic acid)
the first 3 rounds happen without issue. At round 4, a cis double bond is at C3 and C6 (cis and in the wrong place). Isomerase converts C3 cis to trans at C2. Now it’s in the right spot, but the bond at C6 is in the way. Round 4 completes, round 5 step 1 occurs and a trans-C2 is produced as usual. Now the cis-C4 is in the way of step 2 occurring. Reductase eliminates the cis-C4 bond
in what organism are odd numbered FAs common in (2)
many plants, or produced by fermentation of carbs in the stomach chambers of ruminants
what commercial application do odd numbered FAs have
they’re used as mold inhibitors in bread
which round of oxidation is impacted by having an odd numbered FA
the last round
when oxidizing an odd numbered FA, what molecule do we have right before the last round occurs (instead of acetyl-CoA)
propionyl-CoA (3C)
starting from propionyl-CoA (3C), explain how we oxidize odd numbered FAs
propionyl-CoA is carboxylated = 4C methylmalonyl-CoA. This requires bicarbonate, ATP, and biotin attached to the propionyl-CoA carboxylase enzyme. Methylmalonyl-CoA is isomerized and then rearranged by a mutase = succinyl-CoA, which then enters the CAC
what is the end result/product of oxidation of odd numbered FAs
succinyl-CoA (4C) entering the CAC
in the oxidation of odd numbered FAs, what vitamin does the mutase require
B12 derivative
in the oxidation of odd numbered FAs, what does the mutase do?
it exchanges an alkyl group off one carbon with a hydrogen off another
where does oxidation of long chain FAs take place
the peroxisome
list 4 things that peroxisomes do
carry out oxidation reactions and produce H2O2, catalase converts H2O2 to water or uses it to oxidize something else, FA/uric acid/AA breakdown, some synthesis of cholesterol/bile salts
T or F: the sequence of b-ox reactions are the same in the mitochondria and peroxisomes
true
which step of b-ox in peroxisomes differs to b-ox in mitochondria
step 1
describe how step 1 of b-ox in peroxisomes is different to step 1 in mitochondria
mito: electrons given to FAD end up in the ETC to make ATP
peroxisome: electrons given to FAD pass directly to O2 to make H2O2, which is cleaved to H2O and O2 by catalase. No ATP is made and the energy is dissipated as heat
T or F: in step 1 of b-ox in peroxisomes, ATP is generated by FAD brining electrons to the ETC
false: the electrons given to FAD pass directly to O2 to make H2O2, which is cleaved into water and oxygen. No ATP is made
which long chain FA do we get from eating dairy and certain animal fats?
phytanic acid
microbes in ruminant guts produce phytanic acid derivatives as they digest ________
chlorophyll a
T or F: b-ox is used for branched FAs (phytanic acid)
false; it can’t be used because a methyl group blocks the b carbon
if we can use b-ox for branched FAs, what do we use?
a-oxidation
what is a-oxidation
an OH is placed on the a carbon instead of the b carbon
which carbon gets an OH in a-ox
the a carbon
where does branched FA oxidation take place in the cell
peroxisome
what molecule do we get at the end of a-ox
propionyl-CoA which is converted to succinyl-CoA (same as we saw with odd numbered FAs in b-ox)
FA oxidation is tightly regulated to only occur when the organism ____ ____
requires energy
T or F: FA oxidation occurs when there is lots of potential fuel around (ie glucose)
false; it only occurs when the organism requires energy. The process is tightly regulated
what is the commitment step for b-ox
carnitine shuttle bring fatty acyl-CoA into the mitochondria
which molecule inhibits acyltransferase I? why?
malonyl-CoA. It’s unique to FA synthesis, and we don’t want synthesis and oxidation happening at the same time
when will malonyl-CoA inhibit carnitine acyltransferase I?
when there is ample glucose
describe inhibition of FA oxidation when you ingest carbs
insulin dependent protein phosphatase dephosphorylates acetyl-CoA carboxylase to activate it. ACC then converts lots of acetyl-CoA to malonyl-CoA, and malonyl is then used to make FAs and prevent FA ox from happening
describe activation of FA oxidation when you don’t ingest carbs (3)
glucagon activates PKA which phosphorylates ACC to inactivate it. No malonyl-CoA is made = no inhibition of carnitine acyl-transferase I and this fatty-acyl groups into the mito for b-ox
as well, low ATP activates AMP kinase, which phosphorylates and inactivates ACC
glucagon also triggers free FA mobilization from adipocytes, accessing a huge pool of potential fuel for b-ox
what happens to FA ox regulation when there is low ATP during fasting
activates AMP kinase, which phosphorylates and inactivates ACC = increased ox
what does w-oxidation do
attacks the two carbons on the methyl end of the FA instead of the carboxyl end
where in the body + where in the cell does w-ox occur
ER of liver and kidney cells
when will w-oxidation occur
it substitutes for b-ox if that pathway is defective
are ketone bodies water soluble?
yes
are ketone bodies blood soluble?
yes
are all ketone bodies ketones?
no
where in the body are ketone bodies made
liver
what are ketones made from
acetyl-CoA
when will ketone bodies be made from acetyl-CoA
when there’s no incoming glucose
which 3 ketone bodies can be made from acetyl-CoA
acetone, acetoacetate, D-B-hydroxybutyrate
what happens to the ketone body “acetone” when its in the body
it’s exhaled (sweet fruity breath)
what happens to the ketone bodies “acetoacetate and D-B-hydroxybutyrate” when they’re in the body
they’ll be transported in the blood from the liver to other tissues where they’re reconverted to acetyl-CoA and enter the CAC
which does the brain prefer as fuel: glucose or ketone bodies
glucose
when will the brain use ketone bodies as fuel
under starvation conditions when there’s no glucose
T or F: fatty acids can be used by the brain for fuel
FALSE! only ketone bodies can, which come from fat. FAs themselves cannot be used as fuel because they cannot cross the blood brain barrier
why can ketone bodies (fat derivatives) be used for fuel by the brain but FAs can’t be?
FAs cannot cross the blood brain barrier. Ketone bodies are water and blood soluble, so they can
what is the first step of ketone body synthesis
2 acetyl-CoA –> acetoacetyl-CoA by thiolase
which enzyme converts 2 acetyl-CoA into acetoacetyl-CoA to make ketone bodies?
thiolase
ketone body synthesis: what happens once we have 4C acetoacetyl-CoA
condensation with another acetyl-CoA occurs = HMG-CoA
where does HMG-CoA production occur in FA synthesis? Ketone synthesis?
cholesterol synthesis = cytosol
ketone synthesis = mitochondria
ketone body synthesis: once HMG-CoA is made, what happens
it’s cleaved into acetoacetate by HMG-CoA lyase
ketone body synthesis: which enzyme cleaves HMG-CoA into acetoacetate
HMG-CoA lyase
ketone body synthesis: once we have acetoacetate, how do we get the other two ketone bodies?
via enzymatic modification
is the formation of acetone from acetoacetate reversible or irreversible
irreversible
is the formation of D-B-hydroxybutyrate from acetoacetate reversible or irreversible
reversible
once ketone bodies have been made in the liver, where do they go
they’re shipped off to other tissues
once acetoacetate and D-B-hydroxybutyrate are in the mitochondria of extrahepatic tissues, what can happen?
they can each be reconverted to 2 acetyl-CoA molecules which can then enter the CAC and ETC and make ATP
ketosis: without glucose, what happens to CAC intermediates?
they’re diverted to use for GNG. This slows the CAC and acetyl-CoA stops being oxidized
ketosis: what happens to the build-up of acetyl-CoA when the CAC is slowed down?
acetyl-CoA is shifted to make ketone bodies
ketosis: what happens to excess ketones in the body
released into blood/urine
list 3 ways on how to enter ketosis
- fast / intermittent fast
- very low carb diet
- untreated diabetes
how do you get ketoacidosis
excess ketones in the body (2 out of the 3 are acidic and will lower the blood pH)
extreme ketoacidosis can lead to __ or __
coma or death
T or F: diabetic people have a higher risk for ketoacidosis
true; they already have too many ketone bodies
what does MCAD stand for
medium-chain acyl-CoA dehydrogenase
what is MCAD responsible for
FA oxidation of C6-C12 chains
list 5 things that happen when you have MCAD deficiency
- fat accumulation in liver
- high levels of FAs in blood
- low blood glucose
- lethargy, seizures, brain damage, coma
- 25%-60% mortality in early childhood
how much FA oxidation is able to occur when you have MCAD deficiency (ie how short can you get the FAs)
medium chain
can you produce ketones with MCAD deficiency?
no!
with MCAD deficiency, can you do GNG when glucose is low?
no!
T or F: with MCAD deficiency, you cannot produce ketones or glucose (from GNG)
true! which sucks so bad because you can’t get fuel to your brain
how might you treat MCAD deficiency
make sure that blood glucose levels never drop, because then you’ll never have to oxidize fats to get your fuel
how does one get Zellweger syndrome
arises from an inability to make peroxisomes and thus oxidize very long chain FAs (so they have nowhere to go)
list some symptoms of zellweger syndrome
enlarged liver, hypomyelination of neurons, vision/hearing loss, carniofacial abnormalities, skeletal abnormalities
T or F: humans can excrete ethanol directly
false; they must metabolite it in two step process
where in the body is ethanol metabolized
liver
list the products/reactants of ethanol metabolism
ethanol –> acetaldehyde –> acetate
does ethanol consumption increase or decrease NADH stores
increase
how does ethanol consumption influence PKA activity
reduces it
ethanol intake: how might increased NADH affect b-ox
down regulates b-ox, which needs NAD+
ethanol intake: how might increased NADH affect FA synthesis
converted to NADPH, which then promotes FA synthesis
ethanol intake: how might increased acetate affect FA synthesis
converted to acetyl-CoA, which then promotes FA synthesis
ethanol intake: how might downregulated PKA activity affect b-ox
TAGs in adipocytes no longer properly metabolized upon hormone signals
T or F: overall, increased ethanol intake increases FA synthesis, and in turn increased risk of type II diabetes
true
high fat diet: how would a lack of carbs affect the processing of fats by b-ox?
you’d make lots of acetyl-CoA, which needs to enter the CAC. To enter, it joins with OAA to make citrate. Most OAA is formed by carboxylation of pyruvate, but most pyruvate comes from glycolysis, but you can’t do CAC because of the lack of carbs. Therefore, the acetyl-CoA will be converted to ketone bodies!
high fat diet: how do you combat the formation of excess ketone bodies/ketosis?
incorporate a supplement of a long chain/odd numbered FA. the final carbons cleaved from b-ox will provide proprionyl-CoA, which is converted to succinyl-CoA, which then enters the CAC = lifts the CAC jam and acetyl-CoA won’t need to make ketones anymore
