VITAMIN B12 -- COBALAMIN
Known as CORRINOIDS -- corrin structure
_________________
Other groups may attach to Co to form:
1.
2.
3.
4.
5.
6.
5 -deoxyadenosylcobalamin (5 -deoxyadenosyl group)
Methylcobalamin (CH3 group)
Cyanocobalamin (CN group)
Hydroxocobalamin (OH group)
Aquocobalamin (H2O)
Nitricobalamin (NO2 group)
_____________are most active as coenzymes
Others can be easily converted into the active forms
Structural formula of vitamin B12 (cyanocobalamin)
Fig. 9-35, p. 311
Absorption:
Once
released from foods by stomach pepsin, free
cobalamin:
Attaches
to R proteins (__________high affinity for
cobalamin) and moves from stomach to small intestine
The R protein is hydrolyzed in ___________and free
cobalamin released
Intrinsic Factor (IF) synthesized in stomach and moved to
proximal small intestine binds to cobalamin (any form)
The complex travels to _______, where the receptors are
present
B12
R
proteins
Stomach
Pyloric
sphincter
Small
intestine
B12 R
IF
R
B12
B12 + R
Vitamin B12
absorption.
IF
B12 R
complex
IF
IF
B12 IF
B12 IF
Ileal
receptor
B12
B12
IF
Fig. 9-36, p. 311
VITAMIN B12 -- COBALAMIN (cont)
Transport:
Following absorption, cobalamins bind to one of three transport
proteins -- __________(TCI, TCII, TCIII)
TCII is the main carrier and it also helps vitamin s uptake by the tissue
Storage:
Although water soluble, it is stored in liver (60% of body stores) and
muscle (30% of stores), primarily in the form of adenosylcobalamin
Due to the stored amount and bacterial production in colon, it takes
several years for a deficiency to develop on a diet poor in B12 or low
absorption
VITAMIN B12 -- COBALAMIN (cont)
Sources:
Only
in ______products -- originates from microorganisms
About
70% of vitamin is ________with cooking
Appreciable amounts can be lost from milk by pasteurization (hence,
milk isn t a good source)
B12
is synthesized by microorganisms found in intestinal tract
If found in plants, it s probably due to contamination
DRI, 1998 (see your table)
It
was raised to 2.4-2.6 g/day
VITAMIN B12 -- COBALAMIN (cont)
Functions:
Serves as coenzyme for many enzymes:
Metabolism of folate (methionine synthetase)
For DNA synthesis (deficiency causes megaloblastic cells to be
released in circulation as macrocytes, but still with normal
hemoglobin, normochromic)
In nerve tissue
Deficiency could cause impaired CHO metabolism and glucose
utilization (methylmalonyl CoA to succinyl CoA)
It is necessary for myelin formation (needs methionine)
SEE TEXT, for folic acid, B12 and B6 interaction and
homocysteine accumulation
Fig. 9-33, p. 305
p. 312a
p. 312b
B12 deficiency
Occurs in stages:
Low serum concentrations, as indicated by low TCII
Low RBC concentrations
Leading to:
Decreased DNA synthesis
Elevated serum homocysteine
Anemia
Neuropathy (decreased methionine)
Methyl THF
homocysteine
methionine
methionine synthetase
THF (active)
coenzyme-B12
__________________________-- severe deficiency
Abnormal cell division in bone marrow (megaloblastic cells)
GI abnormalities (diarrhea, constipation)
Neurological ataxia
Spastic reflexes
Paralysis of muscles and nerves
B12 deficiency risk factors:
Poor
diet -- rarely
About
5% deficiency caused by poor diet, rest by GI
disorders or poor absorption
Could be an issue among pure vegans, although takes long time to
develop
GI
disorders:
Lack
of IF secretion (gastrectomy, impaired gastric mucosa)
Decreased absorptive surface (blind loop, ileal resection,
celiac sprue, ileitis)
Chronic pancreatitis
enzyme secretion impaired, for R protein synthesis
Parasitic
infections (tapeworms)
Elderly (IF insufficiency), alcoholics, GI pts, infants
Assessing B12 status:
Serum
levels (normal 200-900 pg/mL)
Less
than 100 pg/mL -- deficiency
Holo
TCII -- transcobalamin with attached B12 (sensitive)
TCII % saturation
Normally
20% of TCII is saturated with B12
Even early stages of deficiency might show TCII saturation of 5%
Urinary
Not
homocysteine
specific as it could originate from folate deficiency
VITAMIN B6 -- ________________________
Structure
Several vitamers which are interchangeable
Pyridoxine (alcohol) form in vegetables and has low bioavailability
Pyridoxal (aldehide) form in animal food -- unstable and destroyed by
cooking
Pyridoxamine (amine) form in animal food -- also unstable
Pyridoxal-5-phosphate (PLP) -- generally considered the active form
Therefore,
the activity depends on the ability to metabolize
into PLP coenzyme
The synthetic vitamin is in a form of pyridoxine hydrochloride
-- stable
Vitamin B6 structures
Fig. 9-38, p. 316
Most of vitamin B6 metabolism occurs in the liver
Fig. 9-39, p. 316
Vitamin B6 metabolism is dependent on the normal _________status
p. 317
PLP functions:
In
about 60 reactions of amino acids metabolism
Particularly
important reactions of transamination, where
both PMP and PLP are involved as coenzymes
Also:
Synthesis of heme
Synthesis of niacin from tryptophan
Synthesis of histamine from histidine
Synthesis of carnitine, taurine, dopamine
Cleavage of homocysteine
Glycogen catabolism to form glucose 1-phosphate
Action on steroid hormone receptors
Prevents or interferes with hormone binding and by that mediates
hormone uptake
Cysteine synthesis from methionine requires vitamin B6 as PLP
Fig. 9-42, p. 319
Sources:
Meat (chicken, pork, fish), eggs
Low in dairy food
Plant foods (whole grains, seeds, nuts)
Particularly high in the germ of the grain
Easily
destroyed by processing, canning, heating,
freezing, milling
DRI:
See table (about 2 and 1.6 mg/day for men and women)
It depends on protein intake. Formula by which the requirements
were calculated: 0.016 mg vitamin B6/1 g protein
Pyridoxine deficiency:
Rare in US under normal conditions
Takes about 2 months to develop symptoms
Poor appetite, weakness, sleeplessness
Microcytic hypochromic anemia (impaired heme synthesis)
Central and peripheral nervous system disorders (impaired serotonin
synthesis)
Hyperhomocysteinemia
Glucose intolerance (especially in pregnant women)
Dermatological problems (glossitis, stomatitis)
Retarded growth, reproductive capacity
Pyridoxine toxicity -- doses from 300-500 mg/d
Signs are similar to deficiency, mostly ____________
At risk groups
Infants born with low levels of B6
Elderly
Alcoholics (can t convert to PLP)
People on high protein intake
Renal patients (from dialysis losses)
Many drugs interfere with B6 metabolism
Anticonvulsants, corticosteroids, penicillamine
Beneficial effects of B6 supplementation (200 mg/day or more)
_________________ disease pts. on L-dopa
Newborns or other pts. with convulsions and seizures
Alcoholics
Assessing pyridoxine status:
Plasma PLP concentrations
When <10 nmol/L -- deficiency
Tryptophan load test (100 mg tryptophan/kg body wt)
Tryptophan
B6
3-L-hydroxyanthranilic acid
xanthurenic acid ----- urine
