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