13_Biochem Block 4.9 Micronutrients I

Front 1

What two vitamins are made by the body?

Back 1

VitD and Niacin (VitB3)

Front 2

With the exception of VitK and Biotin, where are all vitamins absorbed? Where is VitK and Biotin absorbed? Why?

Back 2

Small intestine - Duodenum, jejunum, ileum. VitK and Biotin are absorbed in the large intestine bc that's where microbes make them.

Front 3

Thiamine:
1. How much required
2. Good sources
3. How is thiamine activated?

Back 3

1. 1mg/d
2. Found in milk, fish, lean meats, fortified breads, fortified cereals.
3. Activated via phosphorylation

Front 4

What three enzymes is Thiamine required for>

Back 4

Transketolase (hexose monophosphate shunt)
Pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase enzymes in TCA

Front 5

Thiamine deficiency causes:

Back 5

Beriberi (I can't I can't) - a disease in nervous system.

Front 6

Who most often gets Thiamine deficiency?

Back 6

Alcoholics - they get Wernike-Korsakoff's syndrome which is characterized by confabulation and amnesia

Front 7

Pantothenic Acid (B5):
1. How much required
2. Good sources

Back 7

1. 5 mg/d
2. Meats, whole grains, broccoli, avocados

Front 8

What are the active forms of Pantothenic Acid (B5)? Where is it?

Back 8

Acyl Carrier Protein. Also in Coenzyme A - it's part of this molecule...in the middle (see p467)

Front 9

What are symptoms of Pantothenic Acid (B5) deficiency/toxicity?

Back 9

1. Deficiency is rare
2. Deficiency causes enteritis, alopecia, dermatitis and adrenal insufficiency
3. Non-toxic

Front 10

Riboflavin (B2) is activated in two steps. 1) To make FMN, it is:
2) To make FAD it is:

Back 10

1) Phosphorylated to become FMN (electron transport chain).
2) Adenylated FMN becomes FAD (cofactor for citric acid cycle).

Front 11

Riboflavin (B2) deficiency and toxicity:

Back 11

Deficiency = sensitivity to sunlight, cracks in lips and corner of mouth (cheliosis), inflammation of the tongue and dermatitis.
Not toxic

Front 12

Niacin (B3):
1. How much required
2. Good sources

Back 12

1. 12mg/d
2. Meat, fish, milk, eggs, nuts

Front 13

How is Niacin activated - in this case, it is converted to something with other molecules:

Back 13

Converted to NAD+ and NADP+ via multi-step process.

Front 14

What are symptoms of Niacin (B3) deficiency/toxicity?

Back 14

1. Dermatitis, diarrhea, dementia, hyperpigmentation and desquamation of sun exposed skin (the four Ds - including death)_

Front 15

Niacin can increase which lipoprotein?

Back 15

HDL

Front 16

Biotin (B7):
1. How much required
2. Good sources

Back 16

1. 30ug/d
2. Liver, legumes, dark leafy vegetables, tomatoes, carrots

Front 17

How does biotin (B7) typically get into the body?

Back 17

It is attached to protein from diet --> protein is degraded to aa where biocytin results (Lys-Biotin) --> biotinidase degrades biocytin to biotin + lysine.

Front 18

What is Biotin highly involved in?

Back 18

Carboxylases

Front 19

What are symptoms of Biotin/Biotinidase deficiency/toxicity?

Back 19

Deficiency: Alopecia, neurological disorders, dermatitis. Consumption of raw egg whites can cause biotin deficiency due to binding of the egg white protein, avidin, to biotin - prevents biotin from being absorbed into the intestine.

Front 20

Pyridoxine (B6):
1. How much required
2. Good sources

Back 20

1. 1.5 mg/d
2. Beans, nuts, legumes, meats, eggs, fish, whole grains, cereals

Front 21

How is Pyridoxine activated?

Back 21

Phosphorylation via PLP

Front 22

What rxn require Pyridoxal Phosphate (PLP)?

Back 22

1. Decarboxylases
2. Aminotransferases
3. Ser/Thr dehydratase
3. Aldolases
4. Hydroxymethyltransferase

Front 23

What are symptoms of Pyridoxin (B6) deficiency/toxicity?

Back 23

1. cracks in lips, corners of mouth, inflammed tongue, peripheral neuropathy, pallegra-like symptoms
2. Toxicity = neurological disorders and numbness

Front 24

Folate (B9):
1. How much required
2. Good sources

Back 24

1. 0.4 mg/d
2. beans, legumes, citrus fruits, dark green leafy vegetables, whole grains and meat

Front 25

How is Folate activated?

Back 25

Via reduction rxn mediated by Dihydrobiopterin reductase

Front 26

What are symptoms of Folate (B9)-VitB12 deficiency/toxicity?

Back 26

1. intestinal atrophy, macrocytic anemia (release of large immature RBCs), inability to produce DNA, neurotube defects, mouth sores and tongue inflammation. An accumulation of cysteine results in CVD, cancer and possibly Alzheimer's disease.

Front 27

Cobalamine (B12):
1. How much required
2. Good sources

Back 27

1. 2.4 ug/d
2. meat, shellfish, milk, and eggs.

Front 28

What is VB12 required for?

Back 28

Methionine Synthase and Methylmalonyl-CoA mutase

Front 29

What are symptoms of Cobalamine (B12) deficiency/toxicity?

Back 29

Same as folate bc the two vitamins are involved in the folate pathway-s-adenosylmethionine cycle.
Pernicious anemia - a deficiency in the intrinsic factor - elderly are prone

Front 30

How is B12 absorbed?

Back 30

Via intrinsic factor (glycoprotein) in the stomach - it mediates uptake into the intestinal cells by binding to a specific receptor.

Front 31

Vit K (p478):
1. What pathway is it involved with?
2. Good sources
3. How is it transported from the intestins to the liver? How is it released to other tissues?
4. What makes it similar to other fat soluble vitamins?
5. How much is required/d

Back 31

1. Blood clotting
2. Liver, egg yolk, spinach, cauliflower , cabbage and synthesized by bacteria in intestine.
3. Via chylomicron. Released via VLDL to other tissues
4. Ring structure and phyto-tail
5. About 5ug/d are required.

Front 32

What does VitK induce side-chain-wise on

Back 32

Carboxy groups

Front 33

VitK transfers a pair of electrons to Glu residue and VitK becomes:

Back 33

Gla residue

Front 34

What enzyme mediates the rxn between Glu and Gla via VitK?

Back 34

Vit K dependent gamma glutamylcarboxylase

Front 35

Vitamin K converts what to what on N-terminal regions of prothrombin?

Back 35

Glu to Gla

Front 36

When Glu's are converted to Gla's on the Prothrombin (Factor II) proteins, what happens to its overall charge?

Back 36

It's overall negative charge increases

Front 37

When Prothrombin is changed to hold a higher negative charge, what is it now capable of doing?

Back 37

IT can interact with membrane phospholipids of platelets via Ca2+ bridge - effectively tethering the coagulation proteins to the lipid phosphatidyl serine on the surface of activated cells such as platelets. This accelerates the production of a clot 10,000 fold.

Front 38

Overall, describe how prothrombin activation leads to cross-linking of fibrin. (p.479)

Back 38

1. Vit K carboxylates prothrombin.
2. Activated prothrombin binds to platelets adjacent to activated Xa
3. Platelet/activated prothrombin mediates cleavage to thromin
4. Thrombin goes on to activate Fibrinogen to Fibrin

Front 39

What is the specific pathway that she wants us to memorize (p. 479)

Back 39

1. Factor 9 activates factor 10
2. Factor 10 activates factor 2 (i.e. prothrombin)
3. Prothrombin is activated to thrombin --> the active molecule

Front 40

Extrinsic vs Intrinsic Pathway?

Back 40

1. Extrinsic pathway involves Tissue Factor from injured cells rather than blood - eg Endothelial cells so specific location for coagulation can be targeted.
2. Intrinsic pathway involves activation of blood cells due to abnormal matrix--> inflammatory rxn (Factor 12 to 11 to 9 to 10 to 2)

Front 41

What factors does VitK convert Glu's to Gla's (4)?

Back 41

7, 9, 10, 2

Front 42

In what form is VitK after it adds a carboxyl group to Glu?

Back 42

Vitamin K epoxide

Front 43

How is Vitamin K epoxide recycled?

Back 43

It is reduced via Vit K epoxide reductase

Front 44

What is the mechanism by which clotting inhibitors work? What are they?

Back 44

Dicoumarol and Warfarin. They inhibit VitK epoxide thereby reducing the amount of VitK available for clotting

Front 45

What is vitamin K made by?

Back 45

Bacteria in the gut.