MCB II Block 3

NOTES TAKEN FROM MICK KASTNER

Water-Soluble
Vitamins
B1, B2, B3, B5, B6, B7/H, B9, B12, C
B1- Thiamin
Makes Thiamin Pyrophosphate (TPP)
Used as coenzymes in reactions carbohydrate fat and protein
metabolism.
Uptake: active transport that is inhibited by alcohol  thiamine
deficiency.
TPP is the co enzyme for oxidative decarboxylation (pyruvate
dehydrogenase, alpha-ketoglutarate dehydrogenase, transketolase,
BCKAD)
 Thiamin Deficiency
Acute: Wernicke-Korsakoff Syndrome
◦ Seen in alcoholics mostly. Memory loss and mental derangements.

Advanced: Beriberi
◦ Wet- affects CV system ( right sided heart failure)
◦ Dry- chronic deficiency pf B1 associated
with high carbohydrate diet
B2- Riboflavin
Becomes FAD and FMN, electron acceptors
Must be given to baby with neonatal jaundice because UV light destroys
B2 in the baby
◦ Link to lecture on Heme 

Deficiency protective against malaria

B3- Niacin
Becomes NAD+ and NADP+
Can be made from Tryptophan.
◦ Trp deficiency makes B3 even more essential than it already is.
Synthesis of NADH is complex and requires B1 and B2-
Multi-vitamin deficiency
Deficiency: Pellagra- weakness, anorexia, photosensitive
dermatitis, advanced Pellegra dementia
common in rural parts of Southern US
B5- Pantothenic Acid
Becomes Coenzyme A (CoASH)
Vital for TCA cycle, fat metabolism, etc.
Deficiency is never observed normally
B6- Pyridoxal Phosphate
Becomes PLP. AKA ◦Glycogen
Pyridoxine/Pyridoxal Phosphorylase
Forms Schiff Base TB treatment includes
Useful for: Isoniazid, which can
◦ Transaminases cause a B6 deficiency***
◦ Non-oxidative
Decarboxylases
◦ Lysyl Oxidase (collagen)
◦ ALA Synthase
B6 deficiency/toxicity
Deficiency likely with Isoniazid administration, alcoholism
Symptoms: Neurological disorders, hypochromic anemia
(sideroblastic anemia), Fe storage issues (likely due to role
in heme synthesis)
**Unique: can be TOXIC at high levels
 Peripheral Neuropathy

Leafy green vegetables!

B9- Folic Acid
Becomes FH4 (carrier of 1C groups) and BH4
(reducing agent- Phe Hydroxylase)
100% must come from diet as folic acid
From plants/bacteria, heat labile!
 Folate Trap- B9
CH3-FH4 donates methyl to B12
CH3-B12 donates methyl to homocysteine to recycle
Methionine
◦ Generates more SAM and prevents homocysteinuria

Deficiency  Macrocytic Anemia

Crucial for pregnancy
◦ Neural tube defects if deficient***
◦ Spina Bifida
B12- Cobalamin
Methylcobalamin, Cyanocobalamin
**Must come from animal sources only!!
2 reactions only:
◦ Methionine Synthase (see previous slide)
◦ Methylmalonyl-CoA Mutase
Deficiency  Methylmalonic acidemia,
pernicious anemia (megaloblastic/macrocytic)
 B12 Absorption and storage
Intrinsic Factor (IF) released from stomach
parietal cells binds B12 in duodenum (basic
env.)
Absorbed in Ileum
B12 binds Transcobalamin II for transport in
body
Extensive storage in body, so symptoms only
present months to years after loss of B12 in
diet
C- Ascorbic Acid
Synthesized from glucuronate pathway, except primates are missing the
last step.
Reducing agent and antioxidant against ROS
Recycled with GSH, NADPH
used in Hydroxylation reactions:
◦ Dopamine  NE, collagen synthesis***, Cholesterol  Bile, Carnitine
synthesis

Found easily in citrus fruits, acerola, bell peppers, etc

Destroyed by high heat and neutral pH
Scurvy
Very rare in western world now
Symptoms appear 1-3 months after deficiency begins
Dry mouth, loose teeth, gum decay, slow wound healing, weakness,
bleeding, etc.
B7/H- Biotin
ABC Carboxylases (ATP, Biotin, CO2)
◦ Pyruvate, AcCoA, Propionyl-CoA – Carboxylases

Deficiency can arise from ingestion of Avidin

◦ Found in raw eggs
◦ Cooking eggs denatures avidin and spares patient of deficiency

Found in dark chocolate

Fat-Soluble Vitamins
A, D, E, K
Why do plants make no cholesterol?
instead make “–ene-based” Vitamins A, E & K
Recall Mevalonate pathway in animals - Squalene assembly uses NADPH to reduce @
step where 2 farnesyl-PP combine to make squalene.
In plants – there is a desaturation, creates stiff double bond; thus no cyclization to
lanosterol, etc - explains why plants produce no cholesterol.
Therefore …
plants produce Phytoenes, Lycopenes, relatives like β-carotene – all w/ many conjugated
double bonds (- CH2=CH-CH=CH2- ); these …
absorb ~ most wavelengths; reflect strong colors (orange → red → purple);
and strongly absorb/detoxify ROS

Lycopenes – esp as in cooked tomatoes - most potent of all

Vitamin A
Retinal (eyes**), Retinol, Retinoic Acid (epithelial
health)
◦ Light is sensed when wavelength changes retinal side
chain from trans to cis, which becomes Rhodopsin and
triggers other steps that are not important right now
Precursor: beta-Carotene, along with Vit A used as
treatment for porphyrias (especially EPP)
Deficiency: Night Blindness! Xerophthalmia (dry
eyes)
Toxicity: Acne and teratogen to embryo
 Vitamin D
UV light activates it in skin
Travels to Liver to add an OH
Travels to Kidney to add the second OH
(Calcitriol)
◦ Triggered by PTH secretion
Actions: Ca/PO4 absorption in GI,
Calcium maintenance of bone
Vitamin D Deficiency
In children: Rickets
◦ Soft bones, bowlegged. Excessive loss of Calcium and bone
mass.
Treatment: give Vitamin D
Best source of Vitamin D- direct sunlight
In adults: Osteomalacia and dementia
Vitamin E
a-Tocopherol
Major use is as an antioxidant and protector of PUFAs
Inhibits platelet aggregation
Deficiency: mild hemolytic anemia
Not recommended for prevention of cancer, etc.
Vitamin K
K for “Koagulation”
Essential in Liver to make factors II, VII, IX, X, C, S
Carboxylation of glutamate residues (gamma
carbon!)
Forms
O
CH3
Dietary, vegetables 
OH H2 OH
O 3
C

Phylloquinone (vitamin K1)

O OO O
O Dicoumarol
CH3
Intestinal Bacteria  CH3
C O
OH CH2
O n
CH3 CH
Menaquinone (vitamin K2)
Synthetic  C O
OH O O O
CH3 CH3 Warfarin

OH O
Menadiol (vitamin K3) C O Menadiol diacetate
(acetomenaphthone)
CH3
 Vitamin K Deficiency
First fat-soluble vitamin to be
depleted
Inhibited by Warfarin (Coumadin)

Hemorrhagic Disease of the

Newborn***
Prolonged Antibiotic usage
◦ Some Vit K is produced by gut flora