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