Lecture 6 - Vitamins Flashcards
Vitamin B12
A vitamin which is normally involved in the metabolism of almost all cells of the body
- Maintains normal function of brain and nervous system
- Formation of blood cells
- DNA synthesis and regulation
How is B12 absorbed?
Intrinsic factor (IF):
- Produced by gastric parietal cells
- B12/IF complex moves to ileum
- Binds to a receptor (transcobalamin) on enterocyte, then absorbed
- B12 released into circulation after lysosomal degradation of transcobalamin
IF not recycled
Vitamin B6: what is it also known as, what does it do, where can it be consumed, where it is absorbed, and how much is required daily?
Also known as pyridoxine
Essential co-factor: conversion of succinyl CoA and glycine into ALA (Aminolevulinic acid) by ALA synthase
Common in fruit, vegetables, cereals and meat
Passive absorption in the jejunum and ileum
Recommended daily requirement: 1.5-2.0mg
The use of vitamin B12 and B6 in mitochondria metabolic pathways?
methylmalonyl-CoA + B12 -> Succinyl-CoA
Succinyl-CoA + B6 -> ALA
ALA -> Haem
The metabolic use of vitamin B12
Vitamin B12 co-factor for two biochemical reactions in the body:
- Assists in the conversion of L-methylmalonyl coenzyme A to succinyl coenzyme A
(vital in Haem synthesis) - Assists in the conversion of homocysteine to methionine
How much vitamin B12 is needed daily?
To maintain body stores: ~1-3µg
Only 1000-3000 units of IF needed
(average basal IF secretion is 3000 units per hour, daily ~ 50,000 units)
Minimum to maintain health (not body stores) ~0.5µg
How is vitamin B12 stored and lost
Storage: Liver - Healthy adult - total body content 3-5mg
Loss: urine and faeces - desquamation of epithelial and excretion in bile, rate of loss - 0.05-0.1% of body content each day
Folates: what are they also known as, how are they obtained, and where can they be obtained?
large numbers of compounds: one being folic acid - Vitamin B9
Humans cannot synthesise folate, so all folate intake comes from the dietary intake.
Folates are found in both animals and plants
Folic acid: how is it utilised, where does absorption occur, how is it converted for metabolic use, and
Folic acid (folate) not the active form must be reduced to tetrahydrofolate (THF)
Absorption takes place in the duodenum and jejunum
Absorbed folates are converted into 5-methyltetrahydrofolate monoglutamate before entering the portal blood system.
Plasma folate circulates bound or unbound to plasma proteins.
What are the metabolic uses of Folic acid?
- Synthesis of purine/pyrimidine precursors of DNA
- Important during periods of rapid cell division and growth –infancy/pregnancy
- Production of healthy red blood cells
Vitamin B12 deficiency: what are the two main causes of deficiency?
Pernicious anaemia - impairs absorption of vitamin B12 as a consequence of a reduction in intrinsic factor
Vegans - no B12 in plants
What other causes are there for folate deficiency, how does folate intake relate to pregnancy, and what drugs aid folate absorption?
- Inadequate presence of folate in food
- Poor dietary habits e.g. chronic alcoholics
- Impaired absorption or metabolism or an increased demand for the vitamin
A predominant condition requiring an increase in the daily intake of folate is pregnancy due to an increased number of rapidly proliferating cells present in the blood - need for folate will nearly double by the third trimester of pregnancy
Certain drugs such as anticonvulsants and oral contraceptives can impair the absorption of folate.
What are the treatments for folate and B12 deficiency?
Closure of the neural tube occurs around the 28th day of pregnancy - incidence of neural tube defects (spina bifida and anencephaly) are reduced by 400µg folic acid supplement/day before conception and during the first month of pregnancy
What issues are related to vitamin B12 and folate deficiency?
- Neural tube closing defects
- Spinal cord and peripheral nerves affected - progressive demyelination of nerve cells thought to result from the increase in methylmalonyl-CoA that results from vitamin B12 deficiency
- Patients commonly feel tingling in their feet with difficulty in gait
- Glossitis (inflammation or infection of the tongue)
- Pernicious anaemia - RBCs not fully perfectly formed, resulting in Megaloblastic anaemia
Why does megaloblastic anaemia occur?
Deficiency of folate reduces conversion of dUMP to dTMP - rate-limiting step in DNA synthesis, DNA synthesis delayed
RNA is not affected to the same degree, so the protein synthesis in the cytoplasm continues at a much faster rate than DNA replication, delayed cell division
Rapidly dividing cells need to replicate their DNA - We need to produce 2 x 10^11 red cells per day to replace those destroyed but DNA synthesis is delayed, so cells get bigger but division is delayed resulting in MEGA blasts in the bone marrow and large red cells in the blood
