Vitamin B12

cytosine; guanine; arginine; proline

A fairly common genetic mutation in TCII results in the substitution of ________ for _______ at base pair 776 and results in the insertion of ______ instead of _________ and diminishes TCII"s ability to bind and transport B12.

TCII; nonspecific

All tissues appear to have receptors for ________ and __________ receptors have been shown to take up the TCI-B12 complex.

active transport; passive diffusion

B12 absorption is via _______ _______ at dietary levels and _______ ________ at high concentrations.

transcobalamins I, II, III

B12 binds to three carrier protein molecules know as what?

transcobalamin and haptocorrin

B12 circulates in the blood bound to what transporter proteins?

little to no; 0.1%

B12 undergoes ____________ degradation prior to excretion and about _________% is excreted through bile.

Pernicious anemia

lack of mature erythrocytes caused by inability to absorb vitamin B12 into the bloodstream

intrinsic factor; parietal

Still inside the duodenum, free B12 bind to _______ ________, a glycoprotein that is synthesized by __________ cells in the stomach.

endocytosis; lysosome; degrade

The TCII-cobalamin complex appears to be taken up by cells by __________ and fusion to _________ that ____________ TCII transporters.

Schilling

The __________ test involved orally administering radioactive B12 and measuring urinary excretion of the vitamin where below normal urinary excretion of B12 suggests impaired absorption.

macrocyclic; pyrrole

Vitamin B12 consists of a _______ ring made of four reduced ______ rings linked together.

-aging -inadequate intake (vegetarians and vegans) -altered gastric pH -parietal cell destruction causing insufficient IF -altered duodenal pH -impaired intestinal integrity or function -resection of portions of stomach/SI -competition -use of nitrous oxide

Vitamin B12 deficiency can be a result of what?

pancreatic proteases

Within the alkaline environment of the duodenum, the R protein is hydrolyzed by ______ _______ and free vitamin B12 is released.

ATP-binding cassette drug transporter; transcoblamin II

Within the enterocyte, B12 is released from the complex with IF and is carried across the ileum's basolateral membrane by ________ ________ ________ ___________ and binds to the protein ________ for transport in portal blood.

R protein; saliva

Within the stomach, the now "free" vitamin B12 next binds to an ____ ________ which originates from the _______.

Serum

______ Vitamin B12 concentrations are commonly measured and reflect both intake and status.

Chaperones

________ are intracellular transport proteins that carry or escort B12 within the cell.

Achlorydria

decrease in gastric acid secretion leading to low pepsin and symptoms similar to pernicious anemia.

3-4 hours; 8-12 hours

Following B12's absorption, the vitamin appears in the blood in about _________ hours and peak levels occurring after about __________ hours.

megaloblastic macrocytic anemia

Deficiency of B12, similar to folate, results in ___________________.

parietal cells; instrinsic factor; pernicious

Destruction of _________, results in the lack of _______ production and results in B12 malabsorption and __________ anemia.

animal

Dietary sources of B12 come primarily from ___________ products.

pepsin and hydrochloric acid

Ingested cobalamins from foods must be released from the food proteins to which they are bound by ________ and _______ in the stomach.

methylmalonic acid

Measurement of ________ _________ is used to assess B12 status and may be the most representative marker of metabolic insufficiency and it would be increased in the blood with a B12 deficiency.

60-80%; 20%

Methycobalamin comprises about ________% and adenosylcobalamin perhaps up to _______% of total blood cobalamin.

50

Overall absorption of B12 with usual intake is estimated at _______%.

cubam receptor

The vitamin B12-IF complex travels to the distal ileum and interacts with the _______ _________ on the brush border membrane of ileal cells.

TCII

Transporter protein that is made in many body cells and carries primarily newly absorbed cobalamin in a one to one ratio in the blood and account for about 20%.

TCI

Transporter protein that transports up to 80% of B12 and is thought to function as a circulating storage form of B12.

TCIII

Transporter protein though to function in the delivery of cobalamin form peripheral tissues back to the liver.

False

True or False: Ingested cobalamins from supplements and fortified foods requires digestion/hydrolysis from proteins?

True

True or False: Unlike other water-soluble vitamins, B12 can be stored in the body for long periods?

receptor

Uptake of B12 into tissues is _______ dependent.

cobalt

Vitamin B12's ring center contains ___________ which is attached to 5,6-dimethylbenzimidazole.

Methylcobalamin

What form of B12 is associated with blood?

Adenosylcobalamin

What form of B12 is the main form of the vitamin that is stored in the liver, kidneys and brain?

Cobalamin

What is another name for Vitamin B12?

75%

What percentage of B12 is reabsorbed in the ileum after binding to IF in the SI?

Zollinger-Ellison syndrome

What syndrome occurs with the presence of a gastrin-producing tumor and results in excessive hydrochloric acid production secondary to the high gastrin.

-Methylcobalamin as a coenzyme for methionine synthase -adenosylcobalamin as a co-enzyme for L-methyl-CoA mutase

What two enzymatic reactions require B12 in humans?

cubilin and amnionless; maybe megalin

What two proteins form the cubam receptor?

Cyanocoblamin

When -CN is attached to the cobalt

Aquo or hydrocobalamin

When -H2O is attached to the cobalt

Hydroxocobalamin

When -OH is attached to the cobalt

5'-deoxyadenosylcobalamin

When 5'-deoxyadenosyl is attached to the cobalt

Methylcobalamin

When CH3 is attached to the cobalt

Liver

Where is B12 mainly stored?

TCII

Which transporter for B12 is the major transporter to tissue?

5'-deoxyadenosylcobalamin (adenosylcobalamin) and methylcobalamin

Which two form of B12 are active as coenzymes in humans?

Cyanocobalamin and hydroxocobalamin

Which two forms of B12 are used in multivitamin supplements and used to fortify foods?