FOLATE AND VITAMIN B12
Learning objectives:
1. Know basic structure of tetrahydrofolate
2. Know the composition and basic features of the C1 unit pool
3. Understand the active methyl cycle and its relationship to methionine catabolism
4. The utilisation of vitamin B12 in relation to this process
Background information
Enzymes are proteins that speed up the reaction by lowering the activation energy
The enzyme does not change but the coenzymes and cofactors do change as a result constant need to be replenished.
Cofactors (stabilise and assist with catalysis)
- mainly metal ions
- coenzymes (non-protein part of the enzyme and involved in transferring).
Coenzymes are non-protein, organic molecules and derivatives of vitamins.
Coenzymes are the organic molecule of cofactors, such as vitamins
Coenzymes and cofactors are additions in protein function especially in electrophilic catalysis
Electrophilic=substrate is an electrophile; catalysis=the speed of a chemical reaction by a catalyse
Examples of coenzymes
Biotin
- vital as it carries 1 carbon unit (carbon dioxide)
- involved in carboxylation (addition of a carboxylic acid group)
Flavin coenzymes
- membrane protein
- involved in oxidation and reduction reactions
nicotinamide coenzyme
- soluble protein
- involved in oxidation and reduction reactions
Pyridoxal phosphate
- amino group transfer cofactor
Cobalamin (VitaminB12)
- involved in alkylation
Tetrahydrofolate (THF)
- is a 1 carbon unit transfer coenzyme but carries it in a different way from biotin
- comes from folic acid
Folic acid- vitamin B9
- Is a coenzyme
- A vitamin of the B complex
- Abundant in green vegetables
- Synthesised by bacteria
- Humans don’t make folic acid and obtain from diet
, - Active form of folic acid is THF
LO1. KNOW BASIC STRUCTURE OF THF
Tetrahydrofolate (THF)
- Structure of THF:
2-amino-4-oxo-6-methylpterin + p-aminobenzoic acid (p-ABA) + Glutamate
THF carries C1 units on N5 or N10 or both
- A critical feature difference between biotin & THF is
Biotin carries 1 C unit (carbon dioxide)
THF can transfer 1 C unit in 3 different oxidation states, which allows C to be transferred in different ways in
different processes at different oxidation levels.
- THF transfers C1 units in 3 different oxidation states
- 3 oxidation states:
1. Methanol
2. Formaldehyde
3. Formate
- Increasing states of oxidation:
Methyl- most reduced
Methylene – intermediate
Formyl, formimino, methenyl – most oxidised
The different THF derivatives:
- N5-Methyl-THF
- N5,N10-Methylene-THF
- N5- Formyl-THF
- N10-Formyl-THF
- N5-formimino-THF
- N5,N10- methenyl-THF
Interchange
In equilibrium with each other
Learning objectives:
1. Know basic structure of tetrahydrofolate
2. Know the composition and basic features of the C1 unit pool
3. Understand the active methyl cycle and its relationship to methionine catabolism
4. The utilisation of vitamin B12 in relation to this process
Background information
Enzymes are proteins that speed up the reaction by lowering the activation energy
The enzyme does not change but the coenzymes and cofactors do change as a result constant need to be replenished.
Cofactors (stabilise and assist with catalysis)
- mainly metal ions
- coenzymes (non-protein part of the enzyme and involved in transferring).
Coenzymes are non-protein, organic molecules and derivatives of vitamins.
Coenzymes are the organic molecule of cofactors, such as vitamins
Coenzymes and cofactors are additions in protein function especially in electrophilic catalysis
Electrophilic=substrate is an electrophile; catalysis=the speed of a chemical reaction by a catalyse
Examples of coenzymes
Biotin
- vital as it carries 1 carbon unit (carbon dioxide)
- involved in carboxylation (addition of a carboxylic acid group)
Flavin coenzymes
- membrane protein
- involved in oxidation and reduction reactions
nicotinamide coenzyme
- soluble protein
- involved in oxidation and reduction reactions
Pyridoxal phosphate
- amino group transfer cofactor
Cobalamin (VitaminB12)
- involved in alkylation
Tetrahydrofolate (THF)
- is a 1 carbon unit transfer coenzyme but carries it in a different way from biotin
- comes from folic acid
Folic acid- vitamin B9
- Is a coenzyme
- A vitamin of the B complex
- Abundant in green vegetables
- Synthesised by bacteria
- Humans don’t make folic acid and obtain from diet
, - Active form of folic acid is THF
LO1. KNOW BASIC STRUCTURE OF THF
Tetrahydrofolate (THF)
- Structure of THF:
2-amino-4-oxo-6-methylpterin + p-aminobenzoic acid (p-ABA) + Glutamate
THF carries C1 units on N5 or N10 or both
- A critical feature difference between biotin & THF is
Biotin carries 1 C unit (carbon dioxide)
THF can transfer 1 C unit in 3 different oxidation states, which allows C to be transferred in different ways in
different processes at different oxidation levels.
- THF transfers C1 units in 3 different oxidation states
- 3 oxidation states:
1. Methanol
2. Formaldehyde
3. Formate
- Increasing states of oxidation:
Methyl- most reduced
Methylene – intermediate
Formyl, formimino, methenyl – most oxidised
The different THF derivatives:
- N5-Methyl-THF
- N5,N10-Methylene-THF
- N5- Formyl-THF
- N10-Formyl-THF
- N5-formimino-THF
- N5,N10- methenyl-THF
Interchange
In equilibrium with each other
