Haem B12/B9 Metabolism Flashcards
What are the uses B12
-RBC formation
-DNA Synthesis
-Nervous system formation
- Conversion of L-methylmalonyl CoA to Succinyl CoA
-Conversion of homocystine to methionine
what is the process of absorption of B12
-Mouth to stomach by food protein or TC1 complex broken by pepsin
-B12 binds to R-protein or TC1 and goes to duodenum
-Trypsin breaks the complex and B12 binds to IF
(IF made from parietal cells of stomach)
-IF:B12 complex enters enterocyte via receptor mediated endocytosis.
- acidic environ in endosomes break the complex and lysosomes destroy IF.
B12 binds to TCII and enters blood stream.
What are some key points of the enterocyte for B12 absorption?
-receptors on micrivillus of enterocytes are Cubulin.
-Ca2+ and neutral pH and needed for the receptore mediated endocytosis.
What are the three types of Transcobalamin?
TC1- aka haptocorrin aka R-protein
Binds to B12 in saliva and gastric juices
protects b12 from acidity and transports b12 all the way to intestines
TC2II
Synthesized in liver
High affinity for B12
Main transport protein for B12 in blood
TCIII
Found in placenta
transport B12 from mother to foetus
Importance of B9
-Pyrimidine synthesis
-Purine synthesis
-Catecholamine synthesis
-Histidine catabolism
-Synthesis of Methionine N-5MTHF donates its methyl to create it from homocystine( occurs in presence of B12)
Process of Absorption of B9
-Dietary folate is ingested in the for of polyglutamate
-Polyglutamate is hydrolyzed to Monoglutamate or N-5-MTHF
by enzyme folate conjugase
-N-5-MTHFBINDS TO FBP (Folate Binding Protein) where it carries it to the jejunum.
-MAXIMAL ABSORPTION IN JENUNUM
-Receptor mediated Endocytosis52
How does B12 deficiency affect B9 and DNA?
B12 deficiency causes folate to be trapped in the inactive methyl- THF form.
-Build up of Methyl-THF hinders DNA synthesis.
Causes of B12 Deficiency
Decreased dietary intake
-Intestinal malabsorption
-Increased demand
-Aging-decreased production of stomach acid and I.F leads to decreased B12 formation.
-Pernicious anaemia- the immune system attacks the parietal cells that produce I.F, inability to absorb Anaemia.
What are some conditions where B12 cannot be absorbed properly?
-Crohn’s Disease
-Celiac Disease
-Gastrointestinal surgery or Gastric Bypass
Anaesthetic nitrous oxides inactivates B12
Results of B12 Deficiency
-Megaloblastic and Pernicious Anaemia
-Mental retardation (rarely develop megaloblastic anaemia)
-Excretion of Methylmalonic acid and homocystine in urine.
-Neuropathy ( imbalance, tingling numbness of hands and feet)
-Gastro-intestinal problems
Causes of B9 Deficiency
-Decreased Dietary intake
-Alcoholism-adversely affects absorption, utilization and storage of folate and also promotes its excretion through kidneys.
-Intestinal malabsorption
-Increased demand
-Kidney Dialysis-
results of b9 folate
-Same as B12 deficiency
-Increased susceptibility to infection: decreased folate weakens the immune system
