lipid degradation: beta oxidation Flashcards
1
Q
beta oxidation converts ____ into ____
A
palmitoyl-CoA into acetyl-CoA
2
Q
what is the name of first step of beta oxidation
A
dehydrogenation
3
Q
describe the first step of b-ox
A
acyl-CoA dehydrogenases catalyze the formation of a trans double bond between a and b carbons. FAD gets reduced to FADH2
4
Q
which enzyme catalyzes the first step of b-ox
A
acyl-CoA dehydrogenase
5
Q
what are the by-products of step 1 of b-ox
A
FADH2
6
Q
name step 2 of b-ox
A
hydration
7
Q
describe step 2 of b-ox
A
water is added to the trans double bond of the a and b carbons = a single bond and an OH on the b carbon
8
Q
name step 3 of b-ox
A
dehydrogenation #2
9
Q
describe step 3 of b-ox
A
another dehydrogenation occurs = a ketone on the b carbon. NAD+ is reduced to NADH
10
Q
what is the by-product of step 3 of b-ox
A
NADH
11
Q
name step 4 of b-ox
A
thiolysis
12
Q
describe step 4 of b-ox
A
thiolysis of the two carboxy-terminal carbons via a free molecule of CoA (cleavage between carbons a-b)
13
Q
what is the end result of the first 4 steps (1 round) of b-ox
A
14C-CoA, acetyl-CoA
14
Q
how many rounds of b-ox are needed to complete the cleavage of palmitate/palmitoyl-CoA
A
7
15
Q
how many acetyl-CoA molecules are we left with after 7 rounds of b-ox
A
8 acetyl CoA
16
Q
after 7 rounds of b-ox, why are we left with 8 acetyl-CoA and not 7
A
each round produces 1 acetyl-CoA, but the last round will produce 2 (when the 4C molecule is cleaved)
17
Q
after 7 rounds of b-ox, how many FADH2 do we have
A
7
18
Q
after 7 rounds of b-ox, how many NADH do we have
A
7
19
Q
after 7 rounds of b-ox, how many H+ do we have
A
7
20
Q
after b-ox, where do FADH2 and NADH go
A
to the ETC to drop off electrons to O2
21
Q
each FADH2 produces ___ molecules of ATP in the ETC
A
1.5
22
Q
each NADH produces ___ molecules of ATP in the ETC
A
2.5
23
Q
each pair of electrons donated to O2 in the ETC produce ___ H2O molecule(s)
A
1
24
Q
how many ATP are produced during ONE round of b-ox. Explain (assuming NADH and FADH2 went to the ETC)
A
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
25
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
26
how many H2O were USED during one round of b-ox
1 H2O used per round
27
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
28
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
29
After b-ox, where do the 8 acetyl-CoA molecules go?
they go to the CAC
30
what is the result of the acetyl-CoA from b-ox going to the CAC
more ATP will be produced!
31
each turn of the CAC produces __ NADH
3
32
each turn of the CAC produces __ FADH2
1
33
each turn of the CAC produces __ CO2
2
34
each turn of the CAC produces __ ATP equivalent (GTP)
1
35
how many rounds of CAC (and subsequent ETC) need to occur
8 (because there are 8 acetyl-CoA's)
36
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
37
combining the numbers from complete b-ox and CAC and ETC, how many ATP do we get
108 (28 + 80)
38
where does b-ox occur in the cell
mitochondria matrix
39
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
40
when considering the cost of 2 ATP needed PRIOR to b-ox, what is the NET ATP number (b-ox, CAC, ETC)
106 ATP
41
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
42
what two enzymes do we need to oxidize an unsat FA
isomerase and reductase
43
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
44
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
45
in what organism are odd numbered FAs common in (2)
many plants, or produced by fermentation of carbs in the stomach chambers of ruminants
46
what commercial application do odd numbered FAs have
they're used as mold inhibitors in bread
47
which round of oxidation is impacted by having an odd numbered FA
the last round
48
when oxidizing an odd numbered FA, what molecule do we have right before the last round occurs (instead of acetyl-CoA)
propionyl-CoA (3C)
49
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
50
what is the end result/product of oxidation of odd numbered FAs
succinyl-CoA (4C) entering the CAC
51
in the oxidation of odd numbered FAs, what vitamin does the mutase require
B12 derivative
52
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
53
where does oxidation of long chain FAs take place
the peroxisome
54
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
55
T or F: the sequence of b-ox reactions are the same in the mitochondria and peroxisomes
true
56
which step of b-ox in peroxisomes differs to b-ox in mitochondria
step 1
57
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
58
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
59
which long chain FA do we get from eating dairy and certain animal fats?
phytanic acid
60
microbes in ruminant guts produce phytanic acid derivatives as they digest ________
chlorophyll a
61
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
62
if we can use b-ox for branched FAs, what do we use?
a-oxidation
63
what is a-oxidation
an OH is placed on the a carbon instead of the b carbon
64
which carbon gets an OH in a-ox
the a carbon
65
where does branched FA oxidation take place in the cell
peroxisome
66
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)
67
FA oxidation is tightly regulated to only occur when the organism ____ ____
requires energy
68
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
69
what is the commitment step for b-ox
carnitine shuttle bring fatty acyl-CoA into the mitochondria
70
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
71
when will malonyl-CoA inhibit carnitine acyltransferase I?
when there is ample glucose
72
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
73
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
74
what happens to FA ox regulation when there is low ATP during fasting
activates AMP kinase, which phosphorylates and inactivates ACC = increased ox
75
what does w-oxidation do
attacks the two carbons on the methyl end of the FA instead of the carboxyl end
76
where in the body + where in the cell does w-ox occur
ER of liver and kidney cells
77
when will w-oxidation occur
it substitutes for b-ox if that pathway is defective
78
are ketone bodies water soluble?
yes
79
are ketone bodies blood soluble?
yes
80
are all ketone bodies ketones?
no
81
where in the body are ketone bodies made
liver
82
what are ketones made from
acetyl-CoA
83
when will ketone bodies be made from acetyl-CoA
when there's no incoming glucose
84
which 3 ketone bodies can be made from acetyl-CoA
acetone, acetoacetate, D-B-hydroxybutyrate
85
what happens to the ketone body "acetone" when its in the body
it's exhaled (sweet fruity breath)
86
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
87
which does the brain prefer as fuel: glucose or ketone bodies
glucose
88
when will the brain use ketone bodies as fuel
under starvation conditions when there's no glucose
89
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
90
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
91
what is the first step of ketone body synthesis
2 acetyl-CoA --> acetoacetyl-CoA by thiolase
92
which enzyme converts 2 acetyl-CoA into acetoacetyl-CoA to make ketone bodies?
thiolase
93
ketone body synthesis: what happens once we have 4C acetoacetyl-CoA
condensation with another acetyl-CoA occurs = HMG-CoA
94
where does HMG-CoA production occur in FA synthesis? Ketone synthesis?
cholesterol synthesis = cytosol
ketone synthesis = mitochondria
95
ketone body synthesis: once HMG-CoA is made, what happens
it's cleaved into acetoacetate by HMG-CoA lyase
96
ketone body synthesis: which enzyme cleaves HMG-CoA into acetoacetate
HMG-CoA lyase
97
ketone body synthesis: once we have acetoacetate, how do we get the other two ketone bodies?
via enzymatic modification
98
is the formation of acetone from acetoacetate reversible or irreversible
irreversible
99
is the formation of D-B-hydroxybutyrate from acetoacetate reversible or irreversible
reversible
100
once ketone bodies have been made in the liver, where do they go
they're shipped off to other tissues
101
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
102
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
103
ketosis: what happens to the build-up of acetyl-CoA when the CAC is slowed down?
acetyl-CoA is shifted to make ketone bodies
104
ketosis: what happens to excess ketones in the body
released into blood/urine
105
list 3 ways on how to enter ketosis
- fast / intermittent fast
- very low carb diet
- untreated diabetes
106
how do you get ketoacidosis
excess ketones in the body (2 out of the 3 are acidic and will lower the blood pH)
107
extreme ketoacidosis can lead to __ or __
coma or death
108
T or F: diabetic people have a higher risk for ketoacidosis
true; they already have too many ketone bodies
109
what does MCAD stand for
medium-chain acyl-CoA dehydrogenase
110
what is MCAD responsible for
FA oxidation of C6-C12 chains
111
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
112
how much FA oxidation is able to occur when you have MCAD deficiency (ie how short can you get the FAs)
medium chain
113
can you produce ketones with MCAD deficiency?
no!
114
with MCAD deficiency, can you do GNG when glucose is low?
no!
115
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
116
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
117
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)
118
list some symptoms of zellweger syndrome
enlarged liver, hypomyelination of neurons, vision/hearing loss, carniofacial abnormalities, skeletal abnormalities
119
T or F: humans can excrete ethanol directly
false; they must metabolite it in two step process
120
where in the body is ethanol metabolized
liver
121
list the products/reactants of ethanol metabolism
ethanol --> acetaldehyde --> acetate
122
does ethanol consumption increase or decrease NADH stores
increase
123
how does ethanol consumption influence PKA activity
reduces it
124
ethanol intake: how might increased NADH affect b-ox
down regulates b-ox, which needs NAD+
125
ethanol intake: how might increased NADH affect FA synthesis
converted to NADPH, which then promotes FA synthesis
126
ethanol intake: how might increased acetate affect FA synthesis
converted to acetyl-CoA, which then promotes FA synthesis
127
ethanol intake: how might downregulated PKA activity affect b-ox
TAGs in adipocytes no longer properly metabolized upon hormone signals
128
T or F: overall, increased ethanol intake increases FA synthesis, and in turn increased risk of type II diabetes
true
129
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!
130
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
