Week 4

Question 1

What is the pentose phosphate pathway?

Answer 1

A metabolic pathway parallel to glycolysis. It generates NADPH and pentoses as well as ribose 5-phosphate, a precursor for the synthesis of nucleotides

Question 2

How is pyruvate formed under anaerobic conditions reduced to lactate?

Answer 2

With electrons from NADH, recycling NADH to NAD+ and allowing continued glycolysis in the process of lactate or alcohol fermentation

Question 3

What is the major catabolic fate of glucose-6-phosphate?

Answer 3

Glycolytic breakdown to pyruvate

Question 4

What makes the pentose phosphate pathway different?

Answer 4

• There is glucose oxidation without ATP production

- oxidation is achieved by dehydrogenation using NADP+, not NAD+

Question 5

Is the primary role of the pentose phosphate pathway catabolic or anabolic?

Answer 5

Anabolic

Question 6

Where does the pentose phosphate pathway operate?

Answer 6

Like glycolysis, it occurs in cell cytosol.

• in rapidly dividing cells (bone marrow, skin, tumour cells) it uses the pentose ribose-5-phosphate to make RNA, DNA, ATP, NADH, FADH2, coenzyme A
• in tissues involved in cholesterol and fatty acid synthesis (liver, adipose tissue, adrenal gland)

Question 7

What are the two steps of pentose-phosphate pathway?

Answer 7

• Oxidative (irreversible)- oxidation of glucose: 3 molecules of glucose-6 phosphate give rise to 3 molecules of CO2 and 3 molecules of 5-carbon sugars
• Non oxidative (reversible)- in tissues that require primary NADPH, the pentose-phosphate produced in oxidative phase are recycled glucose-6 phosphate. Regenerates 2 molecules of glucose-6 phosphate and 1 molecule of the glyceraldehyde 3-phosphate

Question 8

What is the first reaction of pentose phosphate pathway

Answer 8

Oxidation of glucose 6-phosphate generating first molecule of NADPH

Question 9

What does the non-oxidative phase recycle?

Answer 9

Pentose phosphates to glucose-6 phosphates

Question 10

What is transketolase?

Answer 10

A thiamin pyrophosphate (TTP) dependent enzyme. TTP is a cofactor also known as vitamin B1

Question 11

What does the ring of TTP stabilise?

Answer 11

The carbanoin in the dihydroxyethyl group carried by transketolase

Question 12

When is the pentose phosphate cycle complete?

Answer 12

When six pentose phosphates have been converted to five hexose phosphates

Question 13

Why is pentose phosphate pathway especially important in red blood cells? (erythrocytes)

Answer 13

• Mature erythrocytes do not divide, so there is no need for ribose-5-phosphate to be used for nucleic acid synthesis
• Erythrocytes do need a supply of NADPH in order to protect the cell membrane from oxidative damage
• Because the production of NADPH offers a protective mechanism for the reduction of glutathione
• Glutathione is a thiol compound which main function is to maintain a reducing environment in the cells by virtue of its -SH group

Question 14

What is ribose-5-phosphate?

Answer 14

A precursor for nucleotide and nucleic acid synthesis

Question 15

What is oxygen?

Answer 15

The element (O) exists in the air as a diatomic molecule O2, it is a toxic mutagenic gas

Question 16

What is hypoxia?

Answer 16

Changes in supply or demand of o2 can lead to insufficient blood perfusion (ischaemia) and insufficient cellular o2 (hypoxia)
-inadequate o2- insufficient ATP, cellular dysfunction or death

Question 17

What are reactive oxygen species?

Answer 17

Oxygen-containing molecules

Question 18

How are ROS formed?

Answer 18

By redox reactions, electronic excitation or enzymes

Question 19

What are the two species of ROS?

Answer 19

1. Free radical (at least one unpaired electron) - eg superoxide
2. Non-radical

Question 20

What is oxidative stress?

Answer 20

Overproduction of ROS within the cell

Question 21

How are ROS produced by enzymes?

Answer 21

ROS may be produced by several enzymes as the primary function eg NADPH oxidase or as a secondary byproduct eg mitochondrial ETC

Question 22

What is oxidative eustress?

Answer 22

• Eustress is a state of low-level H2O2 maintenance that is associated with physiological redox signalling
• Eustress leads to reversible oxidation of cysteine thiols
• This alters protein structure, activity, localisation
• Can occur through methionine oxidation

Question 23

What is oxidative distress?

Answer 23

• A state of supra-physiological concentration of H2O2 leading to unspecific oxidation of proteins
• This results in altered responses, reversible and irreversible damage to biomolecules causing growth arrest and cell death
• Causes damage to all classes of macromolecules, impairing their function
• products of this damage can cause issues

Question 24

What are disulfide bonds?

Answer 24

Covalent bonds between two sulfur atoms formed by the coupling of two thiol groups

Question 25

What are antioxidants?

Answer 25

• In order to get rid of highly toxic effects of ROS, the cell evolved a plethora of antioxidant mechanisms
• can be divided into enzymatic and non enzymatic

Question 26

How do thioredoxin and glutaredoxin work as antioxidants?

Answer 26

They both take part in disulfide exchange reactions to reduce protein thiols

• Trx reduces thiols through a disulfide exchange reaction
• Oxidised trx then reduced by thioredoxin reductase
• NADPH acts as the terminal electron donor