Micronutrients 2: Water-soluble And Fat (lipid)-soluble Vitamins Flashcards
What did Lucy Will’s discover?
“Will’s factor” to treat macrocytic anaemia in pregnant women
What is Will’s factor?
A nutritional factor in yeast that both prevents and cures macrocytic anaemia
What is macrocytic anaemia? (Large cell anaemia)
Megalobastic anaemia;
Cells cannot produce DNA quickly enough to divide at the correct time
Cells therefore grow too large before division
One cause is a lack of the B group vitamin folate required for DNA synthesis
What are folic acids and its derivatives (b9) known as?
Folates
What do coenzymes derived from folic acid participate in the generation and utilisation of?
Single carbon functional groups (methyl- CH3, methylene- CH2, formyl HCO)
What are folates essential for?
Cell growth and tissue development and must come from exogenous sources since mammals can not synthesis these derivatives de novo (so accessed from veges etc)
What are the three major structural components of folic acid?
- A bicyclic, heterocyclic pteridine ring
- P-amino benzoic acid (PABA)
- Glutamic acid (folic acid is a monoglutamic acid)
What is pteridine ring found in?
A large class of biological pigments- particularly butterfly wings
How many successive reductions converts folic acid to tetrahydrofolate?
2
What happens to folic acid once inside a cell?
It’s converted to active forms by two successive reductions (of the pyrazine part of the pteridine ring)
What are both reactions in the conversion of folic acid to tetrahydrofolate catalysed by?
The NADPH-specific enzyme dihydrofolate reductase
What’s the electron donor/reducing agent in the conversion of folic acid to tetrahydrofolate?
NADPH
What yields a poly-y-glutamate tail in the tetrahydrofolate?
The addition of additional glutamic acid residues in liver cells
What are the derivatives of folate/tetrahydrofolate?
Bacteria and higher plants
What do folate/tetrahydrofolate exist as in bacteria and higher plants?
Polyglutamate (more than one tail)
Where does the conversion of folate into a monoglutamate form (from polyglutamate) occur?
In the intestine where it’s absorbed by active transports
What happens to folate in the intestinal cells?
There’s a conversion into an active form
How many reductase occur in the conversion of folate in intestinal cells?
Two- by dihydrofolate reductase (DHFR)
How much tetrahydrofolate is stored in the liver?
1/2
What happens to tetrahydrofolate in the liver?
There’s the addition of glutamate residues
What does the addition of glutamate residues to tetrahydrofolate do?
- Helps retain tetrahydrofolate inside cells as a poor substrate for anion transporter
- Helps the tetrahydrofolate bind more tightly to enzymes
What is the role of tetrahydrofolate of single carbon units?
To be in the N5 and N10 positions in the THF
What is the carbon unit transfer involved in the synthesis of? (In tetrahydrofolate)
Amino acids
Purines
Deoxythmidine monophosphate
What are the building blocks for DNA/RNA (ie precursors)?
Purines
Deoxythymidine monophosphate
What are folic acid and it’s many derivatives referred to as?
Folates
What do co-enzymes derived from folic acid participate in?
The generation and utilisation of single carbon functional groups; methyl (CH3), methylene (CH2) and formyl (HCO)
What are folates essential for?
Cell growth and tissue development
Where must folates come from?
Exogenous sources since mammals cannot synthesise these derivatives de novo
What is a target of a number of useful anti cancer, antibacterial and antiparasitic drugs
Dihydrofolate reductase (DHFR)
What is antimetabolite?
A synthetic compound, usually structurally related to the metabolite, that interferes with the metabolic to which it is related
What is the anti cancer target to inhibit human dihydrofolate reductase?
Aminopterin and methotrexate
What drug targets antibacterial; inhibits bacterial DHFR?
Trimethoprim
What drug is antiparasitic and inhibits protozoa DHFR?
Prymethamine
What did the concept of antimetabolites as drugs arise from?
The early work on folate metabolism
What changes P-aminobenzoic acid to folic acid in micro organisms?
Dihydropteroate synthetase
What converts folic acid to tetrahydrofolic acid in humans and microorganisms?
Dihydrofolate reductase
What is said to have a protective effect against the development of neural tube defects (NTDs)?
Folate
What is believed to cause NTDs?
Combination of genetic disposition and environmental influences
What results in NTDs?
Failure of closure of neural tube- two main forms depend on whether the cranial or caudal end of the neural tube is involved
What is the most important cranial defect?
Anencephaly
What is anencephaly?
When the cerebral cortex fails to develop, accounts to 1/3 of cases of NTDs, is invariably lethal with death either before or shortly after birth
What is the principal caudal defect?
Spina bifida
What is Spina bifida?
When the spinal cord develops abnormally, accounts for two thirds of NTDs and causes paralysis of the lower extremities and impaired bladder and bowel function, but its not usually fatal unless accompanied by other conditions
What is the methylation hypothesis?
A proposal that folate prevents NTDs by increasing methylation of various molecules that are essential to cellular processes
What is folic acid often included in?
Bread
What are water soluble vitamins?
B
C
What are fat soluble vitamins?
A
E
D
K
