metabolism – questions and answers phase 2 mbchb gastroenterology system block gerhard h. w. may
TRANSCRIPT
Metabolism – questions and answers
Phase 2 MBChBGastroenterology system block
Gerhard H. W. May
Which one is FALSE about lipids?
Triglyc
erides a
re th
e mai...
Some lip
ids conta
in ph...
Fatty acid
s can be use
d f..
Lipids a
re m
ostly hyd
ro...
Lipid abso
rption is
requi...
22%
34%
8%
14%
23%
1. Triglycerides are the main storage form of lipids in the human body
2. Some lipids contain phosphate groups, carbohydrates, or proteins
3. Fatty acids can be used for gluconeogenesis
4. Lipids are mostly hydrocarbon and water-insoluble
5. Lipid absorption is required for the absorption of some vitamins
Which one is FALSE about fat catabolism?
The first st
ep of fat c
atab...
Fatty acid
s first
have to
..
Activa
tion occurs
in the...
The pathway fo
r bre
ak...
Beta oxidation occurs
in...
25%23%
25%
15%13%
1. The first step of fat catabolism is lipolysis
2. Fatty acids first have to be activated to acetyl-CoA
3. Activation occurs in the cytoplasm
4. The pathway for breakdown of fatty acids is termed beta oxidation
5. Beta oxidation occurs in the mitochondrial matrix
Lipid metabolism - overview
CytoplasmMitochondrionMembrane
triglyceride
fatty acids glycerol
fatty acyl-CoA
fatty acyl-carnitinefatty acyl-carnitine
fatty acyl-CoA
acetyl-CoA
citrate cycle
citrate
acetyl-CoA
malonyl-CoA
citrate
b oxidation
lipolysis
activation
fatty acid synthesis
glycolysis dietary carbohydrates
dietary fat stored fat
glycolysis
Which one is FALSE about ketone bodies?
They are fo
rmed in
the l..
.
They diffuse
into
the blo..
They are to
xic to
peripher..
They accumulate as a
by...
They can le
ad to keto
ac...
33%
12%
3%
17%
35%1. They are formed in the liver from acetyl-CoA
2. They diffuse into the blood stream
3. They are toxic to peripheral tissues which prefer glucose
4. They accumulate as a by-product of beta oxidation under conditions of extreme starvation
5. They can lead to ketoacidosis
Ketone bodies
• Formed in liver mitochondria– from acetyl-CoA from b oxidation
• Diffuse into the blood stream and to peripheral tissues• Important molecules of energy metabolism for heart muscle
and renal cortex– converted back to acetyl-CoA, which enters TCA cycle
How often does beta oxidation happen for the breakdown of a C14 fatty acid?
Four ti
mes
Five
times
Six times
Seven ti
mes
Eight ti
mes
10% 9% 10%
41%
31%
1. Four times2. Five times3. Six times4. Seven times5. Eight times
What are the products of the breakdown of a C14 fatty acid?
8 acetyl
-CoA, ...
7 acetyl
-CoA, ...
7 acetyl
-CoA, ...
7 acetyl
-CoA, ...
4%
37%
27%31%
1. 8 acetyl-CoA, 7 NADH + H+, 7 FADH2
2. 7 acetyl-CoA, 6 NADH + H+, 6 FADH2
3. 7 acetyl-CoA, 6 NADPH + H+, 6 FADH2
4. 7 acetyl-CoA, 6 NADH + H+, 6 FADH2, 6 GTP
b oxidation
• Cycle of reactions– in mitochondrial matrix
• Four steps in each cycle
• Products of each cycle:– 1 acetyl-CoA– 1 FADH2
– 1 NADH + H+
– 1 fatty acyl-CoA, shortened by 2 carbon atoms
Acyl-carnitine
TCA cycle
Which one is FALSE about amino acid catabolism?
The amino group of a
mi..
Removal of t
he amino g...
Carbon sk
eletons o
f all .
..
Gluco
genic
amino acids c
..
Ketoge
nic amino acid
s c..
8%15%
11%12%
54%1. The amino group of amino
acids is removed to form urea
2. Removal of the amino group only occurs in liver cells
3. Carbon skeletons of all amino acids can enter the TCA cycle
4. Glucogenic amino acids can be used to form glucose
5. Ketogenic amino acids can be completely oxidised in the TCA cycle
Which one is FALSE about the removal of nitrogen?
Amino groups f
rom ami..
One nitr
ogen of ure
a is .
..
One nitr
ogen of ure
a is .
..
Free ammonium is
toxic
43%
11%18%
28%
1. Amino groups from amino acids are directly transferred to carbamoylphosphate
2. One nitrogen of urea is derived from aspartate
3. One nitrogen of urea is derived from free ammonium
4. Free ammonium is toxic
The urea cycle
• Urea is synthesised in a complex series of reactions– in the liver– urea/ornithine cycle– one nitrogen from free
ammonium, the other from aspartic acid
– carbon from CO2
Which one is FALSE about fatty acid synthesis?
It is
a reducti
ve pro
cess
It occu
rs in th
e cyto
plasm
Citrate
transp
orts ace
tyl...
It re
quires N
ADPH
Fatty acid
synth
ase co
nsis..
10% 8%
45%
17%20%
1. It is a reductive process2. It occurs in the
cytoplasm3. Citrate transports
acetyl groups from mitochondria to the cytoplasm
4. It requires NADPH5. Fatty acid synthase
consists of 7 distinct peptides
Fatty acid synthesis vs. degradationsynthesis degradation
location cytoplasm mitochondrial matrix
intermediates linked to ACP linked to CoA
enzymes single polypeptide separate
cofactors NADPH (reductant) NAD+, FAD (oxidants)
length constraints stops at C-16 no constraints
The donor molecule of carbon atoms to a growing fatty acid is...
Acetyl
-CoA
Malonyl-
CoA
Citrate
Acyl-C
oA
26%30%
10%
34%1. Acetyl-CoA2. Malonyl-CoA3. Citrate4. Acyl-CoA
Acetyl-CoA carboxylase - regulation• Insulin signals the fed state:
– stimulates storage of fuels and synthesis of proteins
• Glucagon signals starved state, epinephrine signals requirement for energy:– mobilise glycogen stores
• Citrate stimulates allosterically:– citrate levels are high when acetyl-
CoA and ATP are abundant• Antagonised by palmitoyl CoA:
– abundant when fatty acids are in excess
What is NOT the meaning of ‘citrate stimulates allosterically’?
Citrate
binds to a si
te se...
Citrate
helps insu
lin to
s...
When th
ere is
lots
of cit..
.
Binding of citr
ate to
acet..
.
Individual
acetyl-C
oA ca...
21%
27%23%
7%
22%
1. Citrate binds to a site separate from the catalytic cleft of acetyl-CoA carboxylase
2. Citrate helps insulin to stimulate the catalytic activity of acetyl-CoA carboxylase
3. When there is lots of citrate it activates acetyl-CoA carboxylase
4. Binding of citrate to acetyl-CoA carboxylase activates the catalytic activity of the enzyme
5. Individual acetyl-CoA carboxylase enzyme molecules can be affected by a number of small molecule effectors, citrate is one of them
Which one is FALSE about glycogen and its synthesis?
Liver g
lycoge
n can se
rve ..
Muscl
e glyco
gen can onl...
Gluco
se has t
o be bound...
Glyc
ogen sy
nthase
can n..
Glyc
ogen sy
nthase
start.
..
0% 0% 0%0%0%
1. Liver glycogen can serve as a source for blood glucose
2. Muscle glycogen can only be used for energy generation in the muscle cell
3. Glucose has to be bound to UDP before it can be transferred onto glycogen
4. Glycogen synthase can not introduce branches
5. Glycogen synthase starts new glycogen molecules by binding one glucose molecule to a glycogenin protein
Countdown
10
What is glycogenin?
• Glycogenin is a protein and sits at the centre of a glycogen polymer• It has catalytic activity and can covalently bind up to four glucose molecules to
itself, essentially forming the starting point of the glycogen polymer• This is important because glycogen synthase can only add glucose residues to an
existing glycogen chain
Glycogen
Glycogeninprotein
Which one is FALSE about glycogen breakdown?
Gluco
se is
rem...
Liver c
ells ca
...
Gluca
gon in
hib...
Insu
lin in
hibi...
0% 0%0%0%
1. Glucose is removed from glycogen as glucose-6-P
2. Liver cells can create free glucose from glycogen
3. Glucagon inhibits glycogen synthesis and stimulates glycogen breakdown
4. Insulin inhibits glycogen breakdown and stimulates glycogen synthesis
Countdown
10
glucose-6-phosphatase
In l
iver
onl
y
glucose-6-phosphatase
glycogen
Glycogen breakdown summary
glucose-1-phosphateRate limiting step
glucose-6-phosphate
glycolysis
Blood via GLUT2transporter
glucose
glycogen phosphorylase
phosphoglucomutase
Which one is FALSE about gluconeogenesis?
It is
a pathwa...
Lacta
te, g
lyce...
It is
glycolys..
.
It occu
rs main...
It is
a very
e...
Gluca
gon sti
mu...
0% 0% 0%0%0%0%
1. It is a pathway for the synthesis of new glucose from non-carbohydrate precursors
2. Lactate, glycerol, and glucogenic amino acids are precursors for gluconeogenesis
3. It is glycolysis run in reverse4. It occurs mainly in the liver5. It is a very energy-consuming
process6. Glucagon stimulates it, insulin
inhibits itCountdown
10
Gluconeogenesis• Requires four unique liver
enzymes
• Proceeds via the synthesis of oxaloacetate in mitochondria– the TCA cycle intermediate
which accepts acetyl groups– important for accepting
acetyl groups from fat breakdown
• Energy consuming
Amino acids are oxidised in the TCA cycle
Amino acids as precursors for gluconeogenesis
Which one is FALSE about metabolism?
Catabolic
path...
Anabolic path
w...
Anabolic path
w...
Anabolic path
w...
Catabolic
path...
0% 0% 0%0%0%
1. Catabolic pathways break down reduced substrates for energy generation
2. Anabolic pathways synthesise oxidised products from small, reduced precursors
3. Anabolic pathways require the input of energy in the form of ATP
4. Anabolic pathways require the input of reducing force in the form of NADPH
5. Catabolic pathways generate reduced cofactors which can drive oxidative phosphorylation 10
ATP as energy currency
Metabolism - redox reactionsADP + Pi ATP
ADP + PiATP
OXIDATIVEPHOSPHORYLATION
H2O O2
NAD+
(FAD)NADH + H+
(FADH2)
NADP+ NADPH + H+
CATABOLISM Oxidised productsReduced fuel
ANABOLISM Oxidised precursorsReduced biosyntheticproducts
Which one is FALSE about glycolysis?
It genera
tes 2
...
It fo
rms t
he f...
It occu
rs in t..
.
It genera
tes t
...
0% 0%0%0%
1. It generates 2 ATP molecules per glucose molecule broken down
2. It forms the first stage of carbohydrate catabolism
3. It occurs in the mitochondrial matrix
4. It generates two NADH + H+ per glucose molecule broken down
10
Glycolysis
• Stage 1: glucose is trapped and destabilised
• Stage 2: two interconvertible three-carbon molecules are formed
• Stage 3: generation of ATP
Pyruvate...
Dire
ctly e
nter..
.
Is co
nverte
d t...
Is co
nverte
d t...
0% 0%0%
1. Directly enters oxidative phosphorylation
2. Is converted to oxaloacetate and is used for fatty acid degradation
3. Is converted to acetyl-CoA and then enters the TCA cycle
10
Which one is FALSE about the TCA cycle?
It pro
vides precu
rsors
for..
.
Breakdown products
fr..
It co
nsumes N
ADH and ...
Carbon sk
eletons o
f ami..
It occu
rs in th
e mito
cho...
0% 0% 0%0%0%
1. It provides precursors for gluconeogenesis
2. Breakdown products from carbohydrate, fat and protein metabolism feed into it
3. It consumes NADH and FADH2
4. Carbon skeletons of amino acids enter it at different points
5. It occurs in the mitochondrial matrix
10
The TCA cycle - overview• Eight reactions in total• A two-carbon unit (from acetyl-
CoA) condenses with a four-carbon unit
• The resulting six-carbon unit is decarboxylated twice– yields CO2
• Four oxidation reactions– yield NADH + H+ and FADH2
• One GTP is formed– energy
• The four-carbon unit is recreated
Which one is FALSE about oxidative phosphorylation?
Electr
ons fro
m...
The electron t..
.
Proto
ns are
pu...
Proto
ns flow b...
Proto
n flow is...
Oxidative
phos...
0% 0% 0%0%0%0%
1. Electrons from NADH and FADH2 are transferred onto O2
2. The electron transport chain is located in the inner mitochondrial membrane
3. Protons are pumped from the intermembrane space to the mitochondrial matrix
4. Protons flow back across the membrane, following their concentration gradient
5. Proton flow is coupled to ATP synthesis
6. Oxidative phosphorylation consists of two separate proton pump systems
Countdown
10
Essence of oxidative phosphorylation
• Electrons from NADH and FADH2 are used to reduce O2 to H2O• Their energy is used to pump protons (H+) from the mitochondrial matrix
to the intermembrane space– pH decreases in intermembrane space, increases in the matrix
• Protons flow back across the membrane, following their concentration gradient
• Energy of proton flow is used to phosphorylate ADP to ATP
Electron transport and H+ pump
• NADH donates electrons to complex I• FADH2 donates electrons to complex II• Complexes I, III and IV pump H+ out while transporting electrons• Electrons are finally transferred onto O2
The P/O ratio...
Is a m
easure
o...
For N
ADPH is 2...
Measu
res the r.
..
0% 0%0%
1. Is a measure of the number of ATP molecules formed per oxygen atom reduced
2. For NADPH is 2.53. Measures the ratio
between NADPH and NADH in the cell
Countdown
10
Which of the following is FALSE about redox potentials?
The redox p
ote...
The more
negat...
Electr
ons can ...
The difference
...
NADH has a
mor..
.
0% 0% 0%0%0%
1. The redox potential of a molecule is a measure of its likelihood to loose an electron
2. The more negative a molecule’s redox potential, the more likely it is to donate an electron
3. Electrons can be transferred from molecules with negative redox potentials to those with more positive redox potentials
4. The difference in redox potentials between substrate and product of a redox reaction relates to the free energy change of the reaction
5. NADH has a more negative redox potential than FADH2, therefore transfer of its electrons to oxygen releases less energy
Countdown
10
Redox potentials
• The standard redox potential E’o of a (reduced) substance X is a measure for how readily X donates an electron (in comparison with H2)
X- X + e-
• A negative E’o means that the reduced form of X has a lower affinity for electrons than H2, a positive E’o means the opposite
Some standard redox potentials
NADH + H+ ‘likes’ to donate electrons more than those molecules below it
Some standard redox potentials
FADH2 has a lower redox potential
Some standard redox potentials
Molecules of the electron transport chain have even lower redox potentials
Some standard redox potentials
Molecular oxygen has the lowest redox potential in this table and is most likely to accept electrons
How are redox potentials related to ATP?
• Electrons are handed from NADH (or FADH2) to molecules of lower redox potential, like a relay baton
• Redox potentials:NAD+/NADH - 0.32 V½ O2/H2O + 0.82 V
• Transferring electrons from a negative to a positive redox potential releases energy
½ O2 + NADH + H+ H2O + NAD+
Go’ = - 220.1 kJ/mol• Oxidative phosphorylation converts the energy inherent in
these electrons into chemical energy in the form of ATP
Difference: 1.14 V
For FADH2: 1.04 V