Block 3 - Bsf: Thf And Vitamin B12

Front 1

Which vitamins are water soluble? List them!

Back 1

B1 (Thiamin)
B2 (Riboflavin)
B3 (Niacin)
B5 (Pantothenic Acid)
B6 (Pyridoxine)
B9 (Folate or folic acid)
B12 (Cobalamin)
B8 (Biotin), and
C (Ascorbic Acid)

Front 2

Which vitamins are fat soluble? List them!

Back 2

D (cholecalciferol)
A (retinol, β-carotenes)
E (tocopherols)
K (phylloquinones; menaquinones)

Dexter Always Enjoys Killing!

Front 3

Cholecalciferol is what type of vitamin?

Back 3

Vitamin D

Front 4

Retinol and β-carotenes are what type of vitamin?

Back 4

Vitamin A

Front 5

Tocopherols are what type of vitamin?

Back 5

Vitamin E

Front 6

Which type of vitamin are phylloquinones and menaquinones?

Back 6

Vitamin K

Front 7

What 2 vitamins are involved in hematopoiesis?

Back 7

Folic acid (B9)
Vitamin B12 (cobalamin)

Front 8

What are some sources of folate?

Back 8

Yeast, liver, and leafy vegetables

Front 9

What are some sources of vitamin B12?

Back 9

Liver, kidney, egg and cheese

Front 10

T/F

Cobalamin is a complicated molecule with different names based on what's attached to it.

Back 10

True!

Front 11

For the production of RBCs and leukocytes in the bone marrow to take place, what 3 things are needed?

Back 11

Nucleotides
Amino acids
Iron

In the bone marrow, the body makes billions of RBCs and leukocytes per hour!

Front 12

What is essential in reactions involving one-carbon transfers?

Back 12

Folic acid

Front 13

What is the coenzyme form of folate?

Back 13

Tetrahydrofolate (FH4)

Front 14

a) How does FH4 participate in metabolic reactions (think o chem)?

b) What types of reactions is it involved with?

Back 14

a) By accepting and donating single-carbon groups

b) Amino acid interconversion and DNA synthesis (purines and pyrimidine thymine).

Front 15

What are these amino acids converted to using TH4?
a) Gly
b) His
c) Homocysteine

Back 15

Gly → Ser
His → Glu
**Homocysteine → Met

Front 16

What 3 active forms does folate exist in?

Back 16

N5Met FH4
N10Formy FH4
N5,N10-methylene FH4

Front 17

a) What is the main circulating form of folate?

b) What form of folate is in 90% of food? How does the body convert it to the circulating form?

Back 17

a) Monoglutamate N5-FH4

b) Three or more glutamate → polyglutamate. In the GI, conjugases remove glutamate to enhance folate absorption. Then, in the liver, monoglutamate is changed back to polyglutamate.

Front 18

FH4 can contain which one-carbon units at different levels of oxidation?

Back 18

Formyl
Methylene
Methyl

Front 19

In what form is folate present in purine synthesis?

Back 19

N10-formyl-FH4

Front 20

In what form is folate present in pyrimidine synthesis?

Back 20

5,10-Methylene-FH4

Front 21

Because of its role in DNA synthesis, folate deficiency may be induced in therapy of what?

Back 21

Cancer

Front 22

a) Methotrexate is an analog of what?

Back 22

Folate

Front 23

Methotrexate is a a)___________ inhibitor of b)_______________, a key enzyme in pyrimidine biosynthesis.

Back 23

a) Competitive

b) Dihydrofolate reductase

Front 24

a) What is 5,10-methylene-FH4's purpose in pyrimidine synthesis?

b) What is the enzyme at this step?

Back 24

a) It transfers a one-carbon unit to dUMP to form dTMP.

b) Thimidylate synthase

Front 25

What diseases is methotrexate used to treat?

Back 25

Rheumatoid arthritis
Psoriasis
Asthma
Alcoholic cirrhosis
Inflammatory bowel disease
Cancer

Front 26

a) What are side effects of methotrexate?

b) Can folate supplements be given along with methotrexate?

Back 26

a) Gastrointestinal distress (diarrhea)
Severe folate deficiency (anemia)

b) Yes, folate supplement reduces drug toxicity, adequate supplements of folate do not reduce methotrexate’s efficiency.

Front 27

What are the best dietary sources of folate?

Back 27

Liver
Fortified cereals
Legumes (garbanzo beans and lentils)
Vegetables (Leafy greens)

Less rich sources:
Eggs
Oranges

Liver:
Chicken, 1 ea 924
Chicken, 1 oz 655
Turkey, 1 ea 500
Beef 4, oz 249
Brewer’s yeast, 1 tbsp 280
Cooked asparagus, 1 cup 263
Cooked lentils, ½ cup 179
Romaine lettuce, 1 ½ cup 114
Orange juice, 8 oz 109
Cooked spinach, ½ cup 103
Cooked broccoli, 1 cup 76
Cooked beets, ½ cup

Front 28

T/F

Deficiency of folate first affects cells that are actively synthesizing DNA.

Back 28

True!

Front 29

Why do RBCs need a continuous supply of folate?

Back 29

Because they turn over every 120 days

Front 30

T/F

Folate is passively transported across the intestinal wall.

Back 30

False!

Hydrolyzed folate is actively transported across the intestinal wall.

Front 31

How are folate supplements absorbed in the intestine?

Back 31

Passive diffusion

Front 32

What drugs can inhibit folate absorption?

Back 32

Alcohol and anticonvulsants

Front 33

What drug interferes with both absorption and storage of folate? (and what is it competing for?)

Back 33

Alcohol competes for transport proteins

Front 34

Is absorption of folate better with or without food?

Back 34

Without food, nearly 100% of the supplement is bioavailable.
With food, as in fortified cereals, its absorption is slightly reduced.

Front 35

How much folate is stored in the body?

Half of it is stored where?

Back 35

5 to 10 mg

Liver

Front 36

A daily intake of 400 μg (RDA) of folate is thought to be _______-preventive.

Back 36

Chemo

Front 37

What disorder can be caused by folate deficiency?

Back 37

Megaloblastic/macrocytic anemia

Front 38

What are 5 possible causes of folate deficiency?

Back 38

Low intake
Inadequate absorption (alcoholism and anticonvulsants)
Increased requirement (pregnancy)
Compromised utilization (Vit. B12 deficiency)
Excessive excretion (long-standing diarrhea)

Front 39

(Early/Late) stages of RBC synthesis in _____________ are the first affected by folate deficiency.

Back 39

Early, bone marrow

Front 40

T/F

RBC and WBC synthesis are both affected by folate deficiency.

Back 40

True!

Front 41

What can folate deficiency cause in the fetus?

Back 41

Neural tube defects

Maternal deficiency of folate:
Spina bifida
Anencephaly

Front 42

T/F

With folate deficiency, you are not able to make DNA, so RBCs grow large, but cannot divide and mature.

Back 42

True!

Front 43

What leads to increased cell size in megaloblastic anemia?

What happens to the oxygen carrying capacity?

Back 43

Continuous hemoglobin synthesis and other cell components.

Without folate to make DNA, cells remain in a large immature form → megaloblasts
(Megaloblasts retain their nuclei)
With fewer mature RBCs released from bone marrow → oxygen carrying capacity decreases → anemia (megaloblastic anemia).

Front 44

What are some signs/symptoms of folate deficiency?

Back 44

Inflammation of the tongue and mouth (glossitis and stomatitis)
Abnormal pigmentation of the skin
Weakness
Tiredness
Diarrhea
Poor growth
Depression
Mental confusion

Front 45

Can megaloblasts carry O2?

Back 45

Nope!

Front 46

What mineral is contained in vitamin B12's complex structure?

Back 46

Cobalt

Front 47

Vitamin B12 is synthesized exclusively by what 3 things?

Back 47

Bacteria
Fungi
Algae

(Plants do not synthesize Vit. B12)

Front 48

How can cows and sheep obtain B12?

Back 48

Bacterial synthesis in their multiple stomachs, or from soil they ingest while grazing.

Front 49

How is B12 in food released from proteins?

Back 49

HCl and gastric juices

Front 50

What does free B12 bind to when ingested?

Where is this synthesized?

Back 50

R-protein (Transcobalamin I/ haptocorrins)

Synthesized by the salivary glands in the mouth.

Front 51

a) Where does the R-protein/ Vit. B12 complex travel to?

b) Then, what releases Vit. B12?

c) Then, _____________, a glycoprotein produced by parietal cells in stomach, binds to Vit. B12.

Back 51

a) Small intestine

b) Pancreatic proteases (e.g. trypsin)

c) Intrinsic factor (IF)

Front 52

a) Where does the IF/Vit. B12 complex travel to?

b) At the ileum, the complex binds to a receptor for ___________.

c) In the _________, what does B12 attach to in order to enter the portal blood?

Back 52

a) Ileum

b) Absorption

c) Enterocytes, transcobalamin II (TCII)

Front 53

What parts of the body take up B12 from the portal blood?

Back 53

Liver
Bone marrow
RBCs

Delivery to tissues is done via receptor for the complex

Front 54

What 2 conversion reactions require B12, and what are their enzymes?

Back 54

Methylmalonyl CoA → succinyl CoA by methylmalonyl CoA mutase

Homocysteine → Met by methionine synthase/ homocysteine methyl transferase

Front 55

Which B12-requiring conversion reaction is the assay for B12 deficiency based on?

Back 55

Methylmalonyl CoA → succinyl CoA by methylmalonyl CoA mutase

Front 56

What is the methyl group donor in Met synthesis?

Back 56

Methyltetrahydrofolate (MTHF)

*This reaction frees THF to participate in DNA synthesis.

Front 57

What is the name of the B12 deficiency that causes death within 2 to 5 years?

Back 57

Pernicious anemia

Front 58

What is juvenile pernicious anemia characterized by?

Back 58

Defective production of intrinsic factor by gastric parietal cells

Front 59

T/F

Symptoms of folate-deficiency anemia are similar to B12 deficiency pernicious anemia.

Back 59

True!

Both have megaloblasts in the blood

Front 60

The cause of pernicious anemia is true Vit. B12 deficiency resulting from hampered absorption of the vitamin.
This is due to the lack of availability of what?

What are possible causes of B12 deficiency?

Back 60

Intrinsic factor

Causes of true Vit. B12 deficiency:
Absence of intrinsic factor (IF)
Absence or defective synthesis of pancreatic proteases
Bacterial overgrowth of the small intestine
Tapeworm infestation
Use of certain antiulcer medications (reduction of acid synthesis)
Chronic malabsorption syndromes (AIDS)
Chronic pancreatic disease
Absence or surgical removal of much or all of the ileum and stomach (Crohn’s disease (Crohn ileitis) )

Front 61

What is the time to develop B12 deficiency from the following mechanisms?

a) Vegan diet
b) Intrinsic factor failure
c) Ileal dysfunction

Back 61

a) 10-12
b) 1-4
c) rapid

Front 62

What are the most nutrient-dense dietary sources of B12?

Back 62

Organ meats (liver, kidneys, and heart)
Seafood
Beef

Food Item and Amount Vitamin B12(ug)
Fried beef liver, 1 oz 31.8
Baked clams, 1 oz 15.6
Steamed oysters, 2 14.4
Roast beef, 3 oz 2.0
Yogurt, 1 cup 1.4
Fortified soy milk, 8 oz 0.9
Beef hot dog, 1 0.9
Boiled egg, 1 0.6
Cooked ham, 3 oz 0.5
Ham lunchmeat, 2 oz 0.4

Eggs
Hot dogs (contain organ meat scraps)
Ham
Milk and milk products

Front 63

What are the 3 possible treatment options for patients with defective B12 absorption?

Back 63

Monthly injection

Use of a vitamin B12 nasal gel

Weekly ingestion of vitamin B12 supplement with megadoses (300 x RDA)
RDA for adult age 19 to 50: 2 μg/day
Over 51 years of age: 2.4 μg/day

Front 64

Why does the FDA recommend intake of both B12 and folate when treating a deficiency, then later rectifying after bloodwork?

Back 64

Because large doses of folate can mask the warning signs of Vit. B12 deficiency

Front 65

B12 deficiency causes nerve degeneration, producing what symptoms?

Back 65

Sensory disturbances in the legs (tingling and numbness)
Paresthesia (burning and prickling)
Loss of concentration and memory
Visual disturbances
Disorientation
Dementia
Sore tongue
In the worst cases, loss of bowel and bladder control

Front 66

SAM (S-adenosylmethionine) is an essential -CH3 donor for what 5 reactions?

Back 66

Norepinephrine → Epinephrine
Guanidinoacetate → Creatine
Nucleotides → Methylated nucleotides
Phosphatidylethanolamine → Phosphatidylcholine
Acetylserotonin → Melatonin

Front 67

Wht is the methyl donor for SAM synthesis?

Back 67

Met

Front 68

What is Met produced from?

What is required in the synthesis of Met?

Back 68

Homocysteine

Vitamin B12

Front 69

The Methyl Trap Hypothesis:

a) In the absence of Vit. B12, THF is trapped in what form?

b) A shortage of the coenzyme form of folate leads to inhibition of DNA synthesis. Therefore, B12 deficiency causes what condition?

c) There will also be an accumulation of what?

Back 69

a) methyl-bound form N5-methyl-FH4 (MTHF)

b) Secondary folate deficiency

c) Homocysteine → homocystinuria

Front 70

Why does hyperhomocysteinemia occur?

Back 70

Homocysteine is derived from S-adenosylhomocysteine after SAM donates its methyl group.

Cystathionine → cysteine → accumulation of cysteine → inhibition of cystathionine synthesis → homocysteine accumulation → release in the bloodstream

Front 71

What product can come from homocysteine being:

a) methylated? (and what is required for this to occur?)
b) condensed with serine?

Back 71

a) Methylated to form methionine (MTHF and Vit. B12 necessary)

b) Condensed with serine to form cystathionine (pyridoxal phosphate/Vit. B6)

Front 72

a) What is high homocysteine linked to?

b) And how can this lead to atherosclerosis (hint: what does it inhibit)?

Back 72

a) Neurological and cardiovascular diseases

b) Inhibition of glutathione peroxidase → low glutathione → increased oxidized LDL → atherosclerosis

Front 73

What can be done clinically to determine the cause of megaloblastic anemia?

Back 73

Measure blood levels of folate and B12

Front 74

T/F

The deficiency of the coenzyme form of folate during pregnancy has been linked to a high risk of neural tube defects in the fetus.

Back 74

True!

Front 75

Intake of folate supplement at what time can decrease the risk of neural tube defects?

Back 75

Before conception, and at least 1 month after conception

Front 76

a) A mutation in N5,N10 methylene-FH4 reductase causes an elevation of _____________ secondary to (folate/B12) deficiency.

b) This mutation makes the enzyme ____________.

c) It causes inhibition of ____ synthesis.

d) N5-methyl-FH4 levels (decrease/increase).

Back 76

a) Homocysteine, folate

b) Thermolabile

c) DNA

d) Decrease

Front 77

Degradation products of what are involved in one-carbon metabolism?

Back 77

Choline

Front 78

Choline can be oxidized to _____________, and then to _____________.

Back 78

Betaine aldehyde, betaine

Front 79

What is a secondary route preventing accumulation of homocysteine?

Back 79

In the liver, betaine or trimethylglycine can donate a methyl group to homocysteine forming methionine

Front 80

If SAM accumulates, what can be methylated to form sarcosine?

Back 80

Glycine

N-methyl glycine = Sarcosine