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NHM 561 > Vitamin B12 (4 questions) > Flashcards

Vitamin B12 (4 questions) Flashcards

1
Q

What are the coenzyme forms of Vitamin B12?

A

Methylcobalamin

5-deoxyadenoslycobalamin

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2
Q

Food Sources of B12

A
  1. Clams
  2. Liver
  3. Fortified yeasts
    …Seafood, Fish (salmon, trout, tuna, haddock)
    …Beef
    …Dairy

Not naturally found in plant-based foods (these are fortified)

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3
Q

R BINDER

A

Secreted into saliva into the mouth

Low pH environment in the stomach favors the binding of cobalamin to R Binder

No action until it binds with cobalamin into the stomach, after pepsin frees B12 from food

Once in the duodenum, biliary and pancreatic secretions degrade R Binder and cobalamin binds with IF

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4
Q

PEPSIN

A

Gastric pepsin releases the food-bound cobalamin in the stomach by breaking down the protein and any food that B12 is a part of

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5
Q

B12 Absorption - - What is in the stomach?

A

Mix of:

-Cobalamin (free form due to pepsin)

-R-Binder

-IF (secreted by parietal cells)

-B12-R Binder Complex (due to HCl acid)

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6
Q

The low pH of the stomach (caused by HCl acid) favors what?

A

FAVORS the binding of B12 to R-Binder in the stomach

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7
Q

IF

A

Secreted in the stomach by the parietal cells

It is along for the ride, until it reaches the duodenum, and will bind to cobalamin, which will move to the ileum

It can bind to cobalamin because biliary and pancreatic secretions degrade R-Binder

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8
Q

B12 Absorption - - What happens in the duodenum?

A

Biliary and pancreatic secretions degrade R-Binder protein, allowing cobalamin to bind to IF, and move to the ileum

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9
Q

IF-B12 Cobalamin Complex

A

Taken up directly into the ileal mucosal cells, through endocytosis, and brought into the cytoplasm, and makes its way to the lysosome

It is split in the lysosome

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10
Q

Where does cobalamin-IF complex split?

A

In the lysosome of the ileal mucosal cells

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11
Q

B12 Absorption - - What happens in the lysosome?

A

IF-Cobalamin complex is split

Cobalamin is bound to TCII (transcobalamin II; a binding protein)

and exits the enterocyte, and enters systemic circulation

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12
Q

How much B12 can be passively absorbed?

A

About 2%

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13
Q

At what oral dose does B12 absorption decrease? Why?

A

Above 0.25 micrograms

The cubilin-amnionless receptors can become saturated, and excess B12 is secreted in the urine

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14
Q

(T/F) B12 is excreted in bile. Explain.

A

TRUE

Bile is synthesized in the liver, taken to the GB, then secreted into the S.I.

a) Bile helps w/ digestion and absorption of lipids
b) Some B12 are part of bile acids and bile salts

Bile can be reabsorbed in the S.I. (including the B12 w/in the bile). This process is the exact same in the ileum. AKA IF is required.

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15
Q

Enterohepatic circulation

A

B12 is excreted in bile but can bind IF in the duodenum and be reabsorbed in the ileum.

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16
Q

TCII

A

Transcobalamin II; binding protein, that binds to cobalamin in the lysosome and then goes to portal circulation, then systemic circulation

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17
Q

Portal Circulation

A

The circulation of nutrient-rich blood between the gut and the liver

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18
Q

What are the 2 receptors for cobalamin-TCII complex?

(on peripheral tissues in systemic circulation)

A
  1. Holo-TCII Receptor
  2. Megalin

Expressed on peripheral tissues

Responsible for bringing the cobalamin-TCII complex into the cell

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19
Q

Once in the cytoplasm (of peripheral tissues), cobalamin is converted to what?

A

Methylcobalamin (coenzyme form)

To be used for homocysteine metabolism

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20
Q

In the mitochondria (of peripheral tissues), cobalamin is converted to what?

A

5-deoxyadenosylcobalamin (coenzyme form)

It is used for propionyl-Coa metabolism

21
Q

In a healthy adult, how much cobalamin is stored?

A

About 2,500 micrograms (2-3 mg)

22
Q

What is the distribution and where is cobalamin stored

A

50% in the LIVER

30% in MUSCLE

20% in pituitary glands, bones, kidney, heart, brain, spleen

23
Q

(T/F) A lot of B12 is lost daily.

A

FALSE - only about 1 microgram a day (very, very low) due to B12 recycling via enterohepatic recirculation

24
Q

How long would it take to see clinical signs of deficiency, in a normal healthy adult?

A

About 2-5 years

Resulting from a complete loss of IF

Seen in the elderly population

25
Q

What is the primary function of methylcobalamin?

A

Needed for methionine and homocysteine metabolism

26
Q

Methionine Synthase

A

This enzyme binds cobalamin

Takes a methyl group from 5-methyltetrahydrofolate (THF) and transfer it to cobalamin, becoming methylcobalamin

Thus converting 5-methylTHF —> THF

27
Q

How is homocysteine created?

A

Methylcobalamin still attached to methionine synthase is going to transfer that methyl group to homocysteine

This creates/synthesizes methionine

28
Q

Methionine

A

Very important AA because it is converted to SAM (S-adenosylmethionine)

29
Q

S-adenosylmethionine

A

SAM

Able to transfer its methyl group to DNA and other proteins
-these thousands of proteins are activated when they receive a methyl group
-this creates SAH

30
Q

S-adenosylhomocysteine

A

SAH

Generated when SAM transfers methyl group to DNA and other proteins

SAH is converted to homocysteine

31
Q

Homocysteine

A

“Bad Guy”

Higher homocysteine is associated with increased risk of CVD, including venous thrombosis, atherosclerosis, high BP, CAD, and stroke
–aka needs to be kept in check

High homocysteine levels are a good indicator if someone has low B12, or folate, or even B6

32
Q

If more methionine is not needed, what happens?

A

Homocysteine can be metabolized ——————————–> Cysathionine
Cystathionine Synthase (PLP dependent; coE of B6)

33
Q

Explain how homocysteine can be converted back to methionine

A

The reaction requires the methyl group from folate to be transferred over to cobalamin, creating methylcobalamin. Then methylcobalamin is going to give its methyl group to homocysteine, therefore synthesizing methionine

34
Q

What is the function of coE form 5-deoxyadenosylcobalamin?

A

It is going to act as a cofactor for the enzyme, methylmalonyl-CoA mutase

-It is the sole function of this coE.

35
Q

Propionyl-CoA

A

a 3-carbon FA that comes from the odd-chain FA metabolism (aka: the 3 carbons leftover from beta-oxidation)
OR it can come from BCAA metabolism

36
Q

Why is MMA bad?

A

MMA = D-methylmalonic acid

associated with destabilizing myelin, and promoting the formation of deformed or highly destabilized myelin

37
Q

Myelin

A

the insulating layer or that sheath that covers nerve cells

helps to transmit the electric impulses (messages) through the nerve, from one nerve cell to another

38
Q

MMA build-up is going to potentially cause….what?

A

Nerve damage; reduced cognition

Been shown that it can inhibit complex II of the ETC, and therefore can cause problems with oxidative phosphorylation (which can result in not having enough biosynthesis of ATP)

39
Q

High blood levels of MMA and low B12 markers, would indicate what?

A

CoE. B12 deficiency of 5-deoxyadenosylcobalamin

40
Q

Megaloblastic Anemia

A

Frank B12 deficiency

appears as multi-lobular/hyper-segmented neutrophils and oval shaped RBCs

41
Q

What population is at increased risk of B12 deficiency? Why?

A

Elderly

Gastritis (acute or chronic)
—Autoimmune gastritis
—H. Pylori infection

Not from lower intakes of B12 except for long-term vegans

42
Q

Autoimmune Gastritis

A

Antibodiesin the stomach that attack parietal cells

Major inflammation prevents those cells from secreting HCl acid, pepsin, and other digestive enzymes

43
Q

H. Pylori infection

A

Bacteria that invade the stomach lining, causing inflammation, blocking secretion of those enzymes that are needed to lower the pH and breakdown food

44
Q

What are secondary deficiency clinical manifestations of B12?

A

Neurological changes (dementia, confusion symptoms)

Due to build-up of MMA and destabilization of myelin

45
Q

Multi-lobular and oval shaped RBCs indicate, what?

A

Megaloblastic anemia (B12 deficiency)

46
Q

How does roux-en-Y gastric bypass cause B12 deficiency?

A

Combination of decreased intake

Lack of IF

Reduced gastric acid

Impaired absorption due to bypass of proximal S.I.

47
Q

What are other subclinical cobalamin deficiency symptoms or clinical manifestations?

A

Any 2 or more:
—Increased MMA
—Increased plasma homocysteine
—Decreased [cobalamin]
—Decreased [holotranscobalamin II]

Individuals s/p RYGB are at increased risk for these.

Not all will be present with frank megaloblastic anemia

48
Q

How is B12 assessed?

A

No gold standard

Will run a panel for all water-soluble vitamins

Use SERUM COBALAMIN (~200-250 ng/L for deficiency)
–Holo-TC II assay
–Serum MMA (indicates B12 deficiency ALONE, if high)
–Serum homocysteine (could be confounded by folate status)

There is no official upper limit

NHM 561 (21 decks)

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