COBALT METABOLISM

Cobalt in food

• High concentrations of cobalt are found in

– fish (0.01 mg/kg),
– nuts (0.09 mg/kg),
– green leafy vegetables (0.009 mg/kg) and
– fresh cereals (0.01 mg/kg), and
• most of the cobalt ingested is inorganic.
• The mean population intake of cobalt is 0.012
mg/day.
• cobalt (as the sulphate) is included in some
multi-constituent licensed medicines, at a
maximum daily dose of 0.25 mg
 Functions of Cobalt and Vitamin B12

• Essential coenzyme for

– Propionate metabolism
• methylmalonyl CoA to succinyl CoA
– DNA synthesis
– Bacterial synthesis of methionine
• Microflora of human intestine cannot use cobalt to
synthesize physiologically active cobalamine.
– Human vitamin B12 requirements must be supplied in
the diet
– Free (nonvitamin B12) cobalt does not interact with the
body vitamin B12 pool.

3
Vitamin B12
 Digestion/Absorption

• Ingested cobalamins must be released from

food matrix
– Attached to polypeptides in foods
– Release occurs via action of pepsin
• Functions at low pH
• Requires adequate HCl production
• Released cobalamin interacts with:
– R-binders (R-protein), Transcobalamin (TCI),
Haptocorrin (Hc)
• R protein (found in saliva and gastric juice)
• Non-specific
• Complex moves from stomach into SI
• In duodenum, R protein is hydrolyzed by proteases
– Inhibited by pancreatic insufficiency
 Absorption

• Cobalamins bind to IF in proximal intestine

– Cobalamin-IF complex travel to ileum
– Binds to receptors and is slowly absorbed into enterocyte
• Can occur by passive diffusion when pharmacologic
amounts are given
– Used for people not producing IF
• Malabsorption occurs
– Achlorydia
– Lack of IF
– Pancreatic insufficiency
• Absorption rate decreases with increased intake
(80% to 3%)
 In Circulation
• Cobalamins bound to one of three proteins
called transcobalamins
– TCI = binds 90% of vitamin B12 and may function
as circulating storage form (hoptocorrin)
– TCII = carries newly absorbed cobalamin to
tissues and helps with uptake of cobalamin
• Receptors on cells for TCII
– TCIII = delivers cobalamin from periphery back to
liver
– Methylcobalamin and adenosylcobalamin found
primarily in blood
• Stored in liver (adenosylcobalamin)
COBALT METABOLISM
 Transport
• TC receptors are degraded upon cellular
uptake to release B12.
• All vitamin within cell is bound to protein:
– Methionine synthetase (cytosol) and
methymalonyl-CoA mutase (mitochondria)
• Distribution in tissues
– Total body store 2-5mg
– Liver (60%)
– Long biological half life: 350-400 days in human.
– Low reserve in infant: about 25 μg.
– Plasma: methylcobalamin (60-80% of total)
 Sources and Intakes

• -microorganisms are able to synthesize B12

• -***humans must obtain B12 and cobalt from
animal foods such as organ and muscle meat
• -***takes a long time to become deficient—
happens in vegetarians
Deficiency
• related to vit B12 deficiency
• macrocytic anemia
• genetic defect: pernicious anemia
 Toxicity

• Polycythemia
• hyperplasia
• Reticulocytosis
• increased blood volume