VITAMIN B12 -- COBALAMIN Known as CORRINOIDS -- corrin structure

_________________ Other groups may attach to Co to form:

1. 5-deoxyadenosylcobalamin (5-deoxyadenosyl group)2. Methylcobalamin (CH3 group)3. Cyanocobalamin (CN group)4. Hydroxocobalamin (OH group)5. Aquocobalamin (H2O)6. Nitricobalamin (NO2 group)

_____________are most active as coenzymesOthers can be easily converted into the active forms

Fig. 9-35, p. 311

Structural formula of vitamin B12 (cyanocobalamin)

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

Stomach proteins R

Pyloric sphincter

Small intestine

Ileal receptor

IF

complex

IF

IF IF

IF R

B12

B12 + R

B12 R B12 R

B12

B12 IF

B12

B12

Fig. 9-36, p. 311

B12 IF

Vitamin B12 absorption.

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 vitamins 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 isnt a good source) B12 is synthesized by microorganisms found in intestinal tract

If found in plants, its 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)

homocysteine methionine

Methyl THF 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 homocysteine Not 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

Fig. 9-38, p. 316 Vitamin B6 structures

Fig. 9-39, p. 316 Most of vitamin B6 metabolism occurs in the liver

p. 317

Vitamin B6 metabolism is dependent on the normal _________status

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

Fig. 9-42, p. 319

Cysteine synthesis from methionine requires vitamin B6 as PLP

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 (cant 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