Regulation of Enzyme Activity Flashcards

1
Q

What is the function of a coenzyme?

What type of molecule typically acts as a coenzyme?

A

They function as carriers of reaction components

e.g. electrons or acyl units

Many water-soluble vitamins are essential coenzymes

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2
Q

Which coenzymes act as carriers of acyl units or carbon dioxide units?

A

Coenzyme A carries acyl units

Biotin and thiamine pyrophosphate carry CO2 units

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3
Q

What is the coenzyme function of riboflavin (B2)?

What does a deficiency result in?

A

FAD, FMN

It results in normochromic-normocytic anaemia

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4
Q

What is the coenzyme function of niacin?

What does a deficiency result in?

A

NAD+, NADP+

Deficiency results in pellagra

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5
Q

What is the coenzyme function of thiamine (B1)?

What does a deficiency result in?

A

Thiamine pyrophosphate

Deficiency results in beriberi

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6
Q

What is the coenzyme function of Vitamin C?

What does a deficiency result in?

A

Prolyl and lysly hydroxylase

Deficiency results in scurvy

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7
Q

What is the coenzyme function of biotin?

What does a deficiency result in?

A

Biotinylated carboxylases

Deficiency results in alopecia, ataxia and seizures

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8
Q

What is the coenzyme function of cobalamin (B12)?

What does a deficiency result in?

A

Cobamide coenzymes

Deficiency results in pernicious anaemia

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9
Q

What is the coenzyme function of folic acid?

What does a deficiency result in?

A

Tetrahydrofolate

Deficiency results in megaloblastic anaemia

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10
Q

What is the coenzyme function of pyridoxal (B6)?

What does a deficiency result in?

A

Pyridoxal phosphate

Deficiency results in peripheral neuropathy, depression, seizures and glossitis

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11
Q

What is the coenzyme function of pantothenic acid?

What does a deficiency result in?

A

coenzyme A

Deficiency results in hypoglycaemia

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12
Q

What is the difference in the pathways that NADH and NADPH are involved in?

A

They are both carriers of reducing power

NADH is involved in energy metabolism

NADPH is involved in biosynthetic reactions

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13
Q

What type of reactions is NADH involved in?

A

Redox reactions

It carries electrons from one species to another

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14
Q

How does the molecular structure of NADPH differ to NADH?

A

NADPH has an additional phosphate group on the ribose sugar of the adenosine nucleoside component

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15
Q

Why will no enzyme work on both NAD and NADP?

A

The presence of the phosphate group on NADP ensures specificity

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16
Q

In which reaction does NAD+ act as a cofactor?

A

The conversion of ethanol to acetaldehyde

This is catalysed by alcohol dehydrogenase

NAD+ is converted to NADH

17
Q

What happens to acetaldehyde after it has been formed from ethanol?

What cofactor is required?

A

It is metabolised to pyruvate by pyruvate decarboxylase

Pyruvate decarboxylate uses biotin as a cofactor

18
Q

What 2 molecules are essential for the metabolism of alcohol to pyruvate?

A

An input of NAD+ and a biotin cofactor

19
Q

What is the most common mutation leading to enzyme defect in humans?

A

Mutations leading to defects in the G6PDH enzyme

This is the glucose-6-phosphate dehydrogenase enzyme

20
Q

What is the role of the G6PDH enzyme?

A

it is part of the first step in the Pentose Phosphate Pathway

This pathway involves making a large amount of the body’s NADPH and ribose-5-phosphate

21
Q

Why must the Pentose Phosphate Pathway be fully active during growth?

A

Active growth requires:

  1. more nucleic acids - this requires ribose-5-phosphate
  2. active biosynthetic pathways - this requires NADPH
22
Q

What does a mutation in G6PDH lead to?

A

The activity of G6PDH is limited, leading to a restricted ability to make NADPH

23
Q

When do people with mutations in G6PDH detect symptoms?

What can this lead to?

A

Carriers do not detect symptoms until there is an increased demand for NADPH

This can trigger a haemolytic crisis and anaemia as red blood cells have a dependence on G6PDH for their NADPH

24
Q

What is the reaction that G6PDH is involved in?

How can this reaction be increased?

A

It converts NADP+ to NADPH

Activity of G6PDH is increased by high levels of NADP+

This increases production of NADPH

25
Q

What are red blood cells reliant on to generate NADPH?

A

They lack mitochondria so are entirely reliant on the PPP to generate NADPH

26
Q

Which drug should be avoided in patients with G6PDH deficiency?

Why?

A

Primaquine - an antimalarial drug

It causes increased generation of peroxides

This damages the RBC membrane and leads to haemolytic crisis

27
Q

In which 3 ways can a G6PDH mutation affect the enzyme?

A
  1. mutations affecting the active site disrupt activity
  2. mutations affecting the regulative site disrupt NADP+ binding
  3. mutations may destabilise the dimer
28
Q

Why can treatment with primaquine induce a haemolytic crisis in some people?

A

It arises as NADPH has an important role in maintaining the levels of reduced glutathione in cells

29
Q

What is the structure of glutathione?

A

It is a tripeptide of glycine, cysteine and glutamic acid

30
Q

What is the role of glutathione in its reduced form?

A

It acts as a sulfhydryl buffer

It keeps the cysteine residues of haemoglobin and other proteins in the reduced state

31
Q

How does glutathione act to stabilise cell membranes?

A

It reduces lipid hydroperoxides

These are produced by the reaction of unsaturated bonds in lipids with hydrogen peroxide

32
Q

What happens to cell membranes if lipid hydroperoxides are not reduced?

A

The hydroperoxides react and cause cleavage of acyl chains

This leads to lysis of red blood cells

33
Q

What is the reaction performed by glutathione to reduce hydroperoxides?

What enzyme is involved?

A

Glutathione reduces the hydroperoxides to alcohols

This is catalysed by glutathione peroxidase

It also produces oxidised glutathione

34
Q

How can oxidised glutathione be converted back to reduced glutathione?

A

By NADPH

This is catalysed by glutathione reductase

35
Q

How can the cell membranes become damaged when there is no NADPH present?

A

Reduced glutathione mops up damaging molecules such as free radicals

Without NADPH, there is no reduced glutathione

The membrane becomes damaged as the molecules are not removed

36
Q

Why does primaquine cause RBC lysis in patients with G6PDH mutations?

A

Primaquine stimulates peroxide formation

This increases the demand for NADPH to a level that the mutant enzyme cannot provide

37
Q

When are thiopurine drugs used?

A

They are used as anti-cancer agents