Chapter 28 Vitamins

Front 1

Energy metabolism

Back 1

1)Thiamine (B1)
2)Riboflavin (B2)
3)Niacin (B3)
4)Biotin
5)Pantothenic acid (B5)

Front 2

Amino Acid metabolism

Back 2

1)B6

- pyridoxine
- pyridoxal
- pyridoxamine

Front 3

RBC/Neural development

Back 3

- Folic acid
- Cobalamine (B12)

Front 4

Collagen synthesis

Back 4

- ascorbic acid

Front 5

Vitamin A

Back 5

- vision
- epithelial tissue
- growth in children

Front 6

Vitamin D

Back 6

- bone mineralization
- blood Ca++ regulation

Front 7

Vitamin E

Back 7

antioxidant

Front 8

Vitamin K

Back 8

clotting factor

Front 9

B1 deficiency

Back 9

- ↓ ATP
- IV glucose can precipitate in alcoholics

Front 10

where is transketolase found?

Back 10

- ribose 5-P --> xylulose 5-P to sedoheptulose 7-P --> glyceraldehyde 3-P

Front 11

FAD

Back 11

- cofactor in succinate dehydrogenase in TCA
- flavin adenine dinucleotide

Front 12

FMN

Back 12

- ETC, accepts 2 e- from NADH in NADH deH rxn
- flavin mononucleotide

Front 13

how is niacin made endogenously?

Back 13

- excess tryptophan produces 10% of RDA

Front 14

what type of reaction does it facilitate?

Back 14

- redox involving a hydride ion transfer

Front 15

Poor man's lipitor

Back 15

- 100x RDA treats type IIb hyperlipoproteinemia

Front 16

Panothenic acid (B5)active form

Back 16

- coA
- part of fatty acid synthase complex

Front 17

B6 active form

Back 17

- pyridoxal phosphate

Front 18

Functions of B6

Back 18

- transamination
- deamination
- decarboxylation
- condensation reactions
- ALA synthase
- synthesis of GABA, 5HT, NE

Front 19

Causes of B6 deficiency

Back 19

- isoniazid (TB drug)
- alcoholics, infants with deficient formula
- women on OCT

Front 20

What is the toxic dose?

Back 20

- neurological symptoms >2g/day

Front 21

cyanocobalamin (B12)

Back 21

- cobalt and corrin ring system

Front 22

5'-deoxyadenosylcobalamin

Back 22

- fatty acid oxidation
- active form

Front 23

methyl cobalamin

Back 23

- active form
- methionine synthesis from homocyteine forming tetrahydrofolate
- isomerization of methyl malonyl CoA from odd chain FA oxidation

Front 24

Reactions that use B12

Back 24

1) Homocysteine via homocysteine methyltransferase to methionine
N5-methyltetrahydrofolate to tetrahydrofolate --> methylcobalamin
2) odd # FA methylmalonyl CoA methylmalonyl CoA mutase (deoxyadenosylcobalamin) --> succinyl coA

Front 25

Steps in B12 metabolism

Back 25

1) Vitamin B12 complexes with R factor in saliva

2) Intrinsic factor (IF) from parietal cells in body + fundus of stomach
- IF necessary for reabsorption in terminal ileum.

3) Pancreatic enzymes cleave off R factor, which allows vitamin B12 to complex with IF

4) Vitamin B12 – IF complex is reabsorbed in terminal ileum

5) After reabsorption, vitamin B12 is bound to transcobalamin in plasma + delivered to metabolically-active cells or stored in liver.

Front 26

Pernicious Anemia

Back 26

- no B12 = no intrinsic factor due to AI destruction of parietal cells
- tx: IM injections of cyanocobalamin
- anemia reversible, but not CNS effects

Front 27

megaloblastic anemia

Back 27

- ↓ in B12 or folic acid --> ↑ in plasma homocysteine levels --> damages blood vessels and poses risk for thrombosis
- tx: folate and B12

Front 28

B12 deficiency

Back 28

- No IF
- low folate and B12
- pure vegan diet
- chronic pancreatitis (can't cleave off R factor)
- terminal ileal disease (Chron's)

Front 29

Source of Biotin

Back 29

- bacterial synthesis in intestine

Front 30

Function of Biotin

Back 30

Cofactor in:
- carboxylation (pyruvate carboxylase and acetyl coA carboxylase, proionyl carboxylase)

Front 31

Biotin deficiency

Back 31

- raw egg whites (avidin)
- broad spectrum antibiotics

Front 32

Folic Acid

Back 32

- tetrahydrofolate deritives
- 1-C transfer reactions in DNA synthesis

Front 33

Metabolism of Folic Acid

Back 33

1) polyglutamates --> monoglutamates in jejunum by intestinal conjugase enzyme
2) Monoglutamate reabsorbed in jejunum
3) circulates as methyltetrahydrofolate
- 3-4 month supply in liver

Front 34

drugs that inhibit folic acid

Back 34

1) methotrexate and trimethoprim inhibit dihydrofolate reductase --> no purine and pyrimidine biosynthesis --> kills blast cells --> macrolytic anemia
2) phenytoin --> I of intestinal conjugase
3) OCP --> block reabsorption of monoglutamate in jejunum
4) EtOH --> block reabsorption in jejunum
5) rapidly growing cancers
6) small bowel malabsorption (celiac disease)
7) sulfa drug inhibits folic acid synthesis

Front 35

methotrexate

Back 35

- inhibits dihydrofolate reductase preventing AA, Purine and thymidine synthesis

Front 36

Sulfonamides

Back 36

- inhibits dihydropteroate synthetase (PABA + pteridine precursor into folic acid)

Front 37

Ascorbic acid

Back 37

- coenzyme in hydroxylation especially proline and lysine
- prevention of formation of free radicals

Front 38

scurvy

Back 38

- vitamin c deficiency
- cigarette smoking

Front 39

Vitamin A components

Back 39

1) retinol
2) retinal
3) retinoic acid

Front 40

precursor of Vitamin A

Back 40

β- carotene

- 2 molecues of retinal liked at aldehyde ends

Front 41

topical form of vitamin A

Back 41

- retinoic acid (all trans)

Front 42

metabolism of vitamin A

Back 42

1) β carotene cleaved by β-carotene dioxygenase in intestine --> retinal
2) retinaldehyde reductase(+ NADPH)reduces retinal to retinol
3)retinol --> palmitic acid --> blood via chylomicron --> liver uptakes and stores as a lipid ester within lipocytes
5) hydrolyzed retinol binds to RBP complex transported to golgi and secreted, in extrahepatic tissues retinol binds to cellular retinol binding protein (CRBP) plasma transport via albumin as retinoic acid

Front 43

β-carotene dioxygenase

Back 43

- cleaves β carotene in intestinal lumen to yield 2 retinal

Front 44

retinaldehyde reductase

Back 44

- reduces retinal to retinol with NADPH

Front 45

transport of retinol from liver to extrahepatic tissue

Back 45

- binding of hydrolyzed retinol to aporetinol binding protein (RBP)

Front 46

aporetnol binding protein (RBP)

Back 46

- liver to extrahepatic tissue by binding to hydrolyzed retinol

Front 47

cellular retinol binding protein (CRBP)

Back 47

- retinol binds within extrahepatic tissues
- moves from cytosol to nucleus

Front 48

How is retinoic acid transported in the plasma?

Back 48

binding to albumin

Front 49

Hormonal action of retinol and retinoic acid

Back 49

- steriod/thyroid hormone superfamily
- earliest processes of embryogenesis --> differentiation of the 3 germ layers. organogenesis and limb development

Front 50

Which vitamins act like steroid hormones?

Back 50

- retinol and vitamin D

Front 51

which form of vitamin A is involved in vision?

Back 51

- 11- cis retinal coupled + opsin to form rhodopsin
- rhodopsin + transducin (G protein)↑ GTP binding
- cGMP --> Na+ channels open
- cGMP phosphodiesterase
- ↓ in cGMP closes channels --> hyperpolaization of rod cell
- with light: 11-cis --> all trans retinal --> activation of transducin -->

Front 52

non visual roles of retinol

Back 52

1) mucous production by phosphorylation of retinol to retinyl phosphate
2) appetite and bone growth
3) spermatogenesis
4) prevention of fetal resorption (retinal and retinol)
5) maintenance of epithelial cells and mucus secretion

Front 53

retinyl phosphate

Back 53

- P activates
- synthesizes glycoproteins and mucopolysaccharides
- similar to dolichol p

Front 54

retinoic acid

Back 54

- required for appetite and bone growt
- used to treat mild acne (Darier's disease)

Front 55

Tretinoin

Back 55

- all- trans retinoic acid
- topical antiaging

Front 56

Isotretinoin

Back 56

- 13-cis retinoic acid
- severe acne (oral)
- teratogenic
- hyperlipidemia
- ↑ LDL/HDL

Front 57

dietary deficiency of vitamin A

Back 57

- night blindness is 1st sign
- ↑ susceptibility to infection and cancer
- xeropthalmia

Front 58

Xeropthalmia

Back 58

- keratinization of the cornea
- severe Vitamin A deficiency

Front 59

Hypervitaminosis A

Back 59

- > 7.5 mg/ day
- dry, pruritic skin
- hepatomegaly
- ↑ Intracranial pressure
- teratogenic

Front 60

storage of vitamin A

Back 60

- retinyl esters in liver and adipose

Front 61

Cholecalciferol

Back 61

- steroid horomone
- 1,25- dihydroxy vitamin D3
- calcitrol

Front 62

Functions of Vitamin D

Back 62

- Ca regulation
- Phosporous homeostasis

Front 63

Ergocalciferol

Back 63

- Vitamin D2
- Plant

Front 64

Cholecalciferol

Back 64

- vitamin D3
- animal

Front 65

7-dehydrocholesterol

Back 65

- endogenous precursor
- --> colecalciferol in dermis and epidermis with sunlight
-

Front 66

Activation of D2 and D3

Back 66

1) 25 hydroxylase in liver
2) 25 cholecalciferol-1-hydroxylase in kidney
3) 1,25-dihydroxycholecalciferol (1,25-diOHD3)

Front 67

Activation of 25 cholecalciferol-1 hydroxylase

Back 67

- ↓ plasma phosphate or Ca (indirectly through PTH)

Front 68

Inhibition of 25-cholecalciferol-1-hydroxylase

Back 68

- feedback inhibition by 1,25 vitamin D3

Front 69

Vitamin D in liver

Back 69

25 hydroylase

Front 70

Vitamin D in kidney

Back 70

25 cholecalciferol-1-hydroxylase

Front 71

Function of Vitamin D

Back 71

- ↑ plasma Ca++
- stimulates Ca and Phosphate uptake by intestine by inducing synthesis of a Ca-binding protein
- ↑ Ca reabsorption by the kidney
- mobilizes bone Ca by reabsorption

Front 72

Rickets

Back 72

- collagen matrix formed by mineralization incomplete
- bow-legged
- mutation in vitamin D receptor --> D- independent rickets

Front 73

Osteomalacia

Back 73

- demineralization of bones
- more severe in northern lattitudes (less sunlight)

Front 74

Renal rickets

Back 74

- chronic renal failure
- low synthesis of 1,25 vitamin D3 (calcitrol)

Front 75

Toxicity of Vitamin D

Back 75

- stored in liver and fat
- loss of appetite, nausea, thirst, stupor, hypercalcemia --> Ca deposits in arteries and kidneys

Front 76

Vitamin K

Back 76

- posttransational carboxylation of blodd clotting factors

Front 77

forms of vitamin k

Back 77

1) phylloquinone --> K1 (plants)
2) menaquinone --> K2 (intestinal bacteria)
3) menadione-->synthetic derivative of K1

Front 78

Requirements of Vitamin K

Back 78

- hepatic synthesis of:
1) prothrombin
2) clotting factors, II, VII, IX and X
- sythesized as inactive precursor molecules

Front 79

what is the formation of mature clotting facotrs dependent on?

Back 79

- vitamin k dependent carboxylation of glutamic acid residue

Front 80

What inhibits the formation of GLA?

Back 80

- dicumarol and warfarin

Front 81

Where is GLA present?

Back 81

- osteocalcin of bone and other unrelated proteins of clotting

Front 82

What is GLA?

Back 82

- γ-carboxyglutamyl residue

Front 83

vitamin K dependent carboxylase

Back 83

- glutamate to γ-carboxyglutamyl residue

Front 84

interaction of prothrombin with platelets

Back 84

- γ-carboxylates chelate Ca, prothrombin --> membrane phospholipids in platelets
- conversion to thrombin

Front 85

Hypothrombinemia

Back 85

- antibiotics can cause in very ill, undernourished patients

Front 86

what have warfarin like activity?

Back 86

- second generation cephalosporins

Front 87

what population is deficient in vitamin K?

Back 87

- newborns with breast milk below RDA

Front 88

toxicity with vitamin K

Back 88

- prolonged treatment --> hemolytic anemia, jaundice in infants (RBC membrane effects)

Front 89

Vitamin E function

Back 89

- antioxidant
- inhibits non-enzymatic oxidation by free radicals
- scavenges peroxy-free radicals
- conjugated to glucuronate and excreted in bile

Front 90

deficiency of vitamin E

Back 90

- premature infants
- defective lipid transport/absorption --> RBC membrane fragility and abnormal cell membranes