Regulation of Enzyme Activity Flashcards
What is the function of a coenzyme?
What type of molecule typically acts as a coenzyme?
They function as carriers of reaction components
e.g. electrons or acyl units
Many water-soluble vitamins are essential coenzymes
Which coenzymes act as carriers of acyl units or carbon dioxide units?
Coenzyme A carries acyl units
Biotin and thiamine pyrophosphate carry CO2 units
What is the coenzyme function of riboflavin (B2)?
What does a deficiency result in?
FAD, FMN
It results in normochromic-normocytic anaemia
What is the coenzyme function of niacin?
What does a deficiency result in?
NAD+, NADP+
Deficiency results in pellagra
What is the coenzyme function of thiamine (B1)?
What does a deficiency result in?
Thiamine pyrophosphate
Deficiency results in beriberi
What is the coenzyme function of Vitamin C?
What does a deficiency result in?
Prolyl and lysly hydroxylase
Deficiency results in scurvy
What is the coenzyme function of biotin?
What does a deficiency result in?
Biotinylated carboxylases
Deficiency results in alopecia, ataxia and seizures
What is the coenzyme function of cobalamin (B12)?
What does a deficiency result in?
Cobamide coenzymes
Deficiency results in pernicious anaemia
What is the coenzyme function of folic acid?
What does a deficiency result in?
Tetrahydrofolate
Deficiency results in megaloblastic anaemia
What is the coenzyme function of pyridoxal (B6)?
What does a deficiency result in?
Pyridoxal phosphate
Deficiency results in peripheral neuropathy, depression, seizures and glossitis
What is the coenzyme function of pantothenic acid?
What does a deficiency result in?
coenzyme A
Deficiency results in hypoglycaemia
What is the difference in the pathways that NADH and NADPH are involved in?
They are both carriers of reducing power
NADH is involved in energy metabolism
NADPH is involved in biosynthetic reactions
What type of reactions is NADH involved in?
Redox reactions
It carries electrons from one species to another
How does the molecular structure of NADPH differ to NADH?
NADPH has an additional phosphate group on the ribose sugar of the adenosine nucleoside component
Why will no enzyme work on both NAD and NADP?
The presence of the phosphate group on NADP ensures specificity
In which reaction does NAD+ act as a cofactor?
The conversion of ethanol to acetaldehyde
This is catalysed by alcohol dehydrogenase
NAD+ is converted to NADH
What happens to acetaldehyde after it has been formed from ethanol?
What cofactor is required?
It is metabolised to pyruvate by pyruvate decarboxylase
Pyruvate decarboxylate uses biotin as a cofactor
What 2 molecules are essential for the metabolism of alcohol to pyruvate?
An input of NAD+ and a biotin cofactor
What is the most common mutation leading to enzyme defect in humans?
Mutations leading to defects in the G6PDH enzyme
This is the glucose-6-phosphate dehydrogenase enzyme
What is the role of the G6PDH enzyme?
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
Why must the Pentose Phosphate Pathway be fully active during growth?
Active growth requires:
- more nucleic acids - this requires ribose-5-phosphate
- active biosynthetic pathways - this requires NADPH
What does a mutation in G6PDH lead to?
The activity of G6PDH is limited, leading to a restricted ability to make NADPH
When do people with mutations in G6PDH detect symptoms?
What can this lead to?
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
What is the reaction that G6PDH is involved in?
How can this reaction be increased?
It converts NADP+ to NADPH
Activity of G6PDH is increased by high levels of NADP+
This increases production of NADPH
What are red blood cells reliant on to generate NADPH?
They lack mitochondria so are entirely reliant on the PPP to generate NADPH
Which drug should be avoided in patients with G6PDH deficiency?
Why?
Primaquine - an antimalarial drug
It causes increased generation of peroxides
This damages the RBC membrane and leads to haemolytic crisis
In which 3 ways can a G6PDH mutation affect the enzyme?
- mutations affecting the active site disrupt activity
- mutations affecting the regulative site disrupt NADP+ binding
- mutations may destabilise the dimer
Why can treatment with primaquine induce a haemolytic crisis in some people?
It arises as NADPH has an important role in maintaining the levels of reduced glutathione in cells
What is the structure of glutathione?
It is a tripeptide of glycine, cysteine and glutamic acid
What is the role of glutathione in its reduced form?
It acts as a sulfhydryl buffer
It keeps the cysteine residues of haemoglobin and other proteins in the reduced state
How does glutathione act to stabilise cell membranes?
It reduces lipid hydroperoxides
These are produced by the reaction of unsaturated bonds in lipids with hydrogen peroxide
What happens to cell membranes if lipid hydroperoxides are not reduced?
The hydroperoxides react and cause cleavage of acyl chains
This leads to lysis of red blood cells
What is the reaction performed by glutathione to reduce hydroperoxides?
What enzyme is involved?
Glutathione reduces the hydroperoxides to alcohols
This is catalysed by glutathione peroxidase
It also produces oxidised glutathione
How can oxidised glutathione be converted back to reduced glutathione?
By NADPH
This is catalysed by glutathione reductase
How can the cell membranes become damaged when there is no NADPH present?
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
Why does primaquine cause RBC lysis in patients with G6PDH mutations?
Primaquine stimulates peroxide formation
This increases the demand for NADPH to a level that the mutant enzyme cannot provide
When are thiopurine drugs used?
They are used as anti-cancer agents
