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Reading material
Principles of Biochemistry with a HumanFocus by Garrett and Grisham, First
Edition, 2002, pages 453-468
Handbook of NonPrescriptions Drugs,
11th edition, Chapter entitled Nutritional
Products by Loyd V. Allen, Jr.
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Vitamins
a group of organic compounds needed in smallquantities in the diet for normal activity oftissues
between 14 20 substances have been identifiedas vitamins
many vitamins act as cofactors, coenzymes or
prosthetic groups for enzymes most vitamins are derived from diet
no calories are derived from vitamins
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Vitamins
first vitamin discovered was thiamine orB1 the term vitamin is derived from the fact
that the substances are needed for life(vita) and because thiamine happened tobe an amine the term was coined as such
however, not all vitamins are amines ornitrogen containing compounds
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Vitamins
vitamin requirements are usuallyexpressed as RDAs (recommended
dietary allowances)
guidelines are provided by 2
organizations:
the Food and Nutrition Board of the NationalAcademy of Sciences- National Research Council
the Food and Drug Administration (FDA)
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RDAs
applications of RDAs include: evaluating the adequacy of the national foodsupply
establishing standards for menu planning
establishing nutritional policy for publicinstitutions/organizations and hospitals
evaluating diets in food consumption studies
establishing labeling regulations
setting guidelines for food product formulation
developing materials for nutritional education
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RDAs
RDAs have limitations: they are too complex for direct consumer use
they do not state ideal or optimal levels of intake
the allowances for some categories are based onlimited data
the data on some nutrients in foods is limited
they do not evaluate nutritional status
they do not apply to seriously ill or malnourished
patients
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Vitamin deficiencies
primary food deficiency crop failure food storage loss
food preparation loss diminished food intake
poverty
anorexia food fadism
chronic diseases
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Vitamin deficiencies diminished absorption
absorption defect
parasites
malignancies
increased requirements
rapid growth increased physical activity
pregnancy
hyperthyroidism
increased loss drug therapy
diuresis
lactation
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Vitamin lossLoss is seen mainly in storage or food preparation
Vitamin A: sensitive to oxygen and light
Vitamin D: usually little loss Vitamin E: sensitive to oxidation especially
when heated or with alkali
Vitamin K: sensitive to acids, alkali, light andoxidizing agents
Vitamin C: very sensitive to oxidation,
especially when heated in contact with metals Vitamin B complex: water solubility results in
loss in cooking water
Riboflavin is sensitive to light
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Vitamins
Vitamins are typically divided into 2groups:
The fat soluble vitamins
A, D, E, and K
The water soluble vitamins
The B vitamins (B1, B2, B3, B6, B7, B12 andpantothenic acid)
Ascorbic acid (vitamin C)
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Bogus vitamins
Vitamin B4 adenine Vitamin B10 identical with folic acid
Vitamin B11
Vitamin B15 pangamic acid
Vitamin B13 orotic acid
Vitamin B17 laetrile Vitamin B19 wormsers secret formula
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Cofactors
provide chemical teeth for enzymes sometimes referred to as coenzymes
enzymes: proteins with catalytic activity
simple enzymes: large protein (polypeptide) that
catalyzes a reaction. The enzyme gets all the tools
(chemical teeth) it needs from the amino acids.
However, there are only 20 different amino acids conjugated enzymes : apoenzyme + cofactor =
holoenzyme
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EXAMPLE:Proteases: enzymes that cleave
peptide bonds
N
N
N
H
R
O
H
R'
O
H
N
OH
H
R
O
+ H2N
N
R'
O
H
H2O
protease
Enzymes perform catalytic reactions such as hydrolysis; the
side chains of amino acids participate in the reactions
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CH2OH
CH2
N
HN
CH2-COOH
all these tools come from amino acidsin the protein active site
Usually electron-rich
side chains are involvedin the catalysis
Aliphatic chains are
normally involved in
hydrophobic interactions
example of a simple enzyme
A serine protease enzyme such as chymotrypsin
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COO- OHN
N
H
ASP HIS SER
COOH O-N
NH
ASP HIS SER
R NH
O
R'
COOH ON
NH
ASP HIS SER
HN O-
R
R'
COO- OHN
N
ASP HIS SER
R
O
R' NH2
H2O
HYDROLYTIC CATALYSIS
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Example of a conjugated enzyme
N
N
R
O
H
H
N
R'
O
Zn+2
OH
cofactor needed for reaction
PRODUCTS + ENZYME
Zinc protease suchas ACE
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Cofactors
all water-soluble vitamins with the exception ofvitamin C are converted/activated to cofactors
only vitamin K of the fat-soluble vitamins isconverted to a cofactor
not all vitamins are cofactors; i.e., lipoic acid isnot a vitamin
cofactors may also act as carriers of specificfunctional groups such as methyl groups andacyl groups
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The water soluble
vitamins
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Pantothenic acid (vitamin B5)
CH2HO C
CH3
CH3
CH
OH
C N
O
CH2
H
CH2 COOH
First recognized in 1933 as a growth factor for yeast (Roger
J. Williams)
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Pantothenic acid
a yellow viscous oil (free acid) stable to moist heat (not to dry heat) and
to oxidizing and reducing agents
hydrolyzed in acid or alkaline medium
sources (numerous): liver, kidney, eggs,
lean beef, milk, molasses, cabbage,cauliflower, broccoli, peanuts, sweetpotatoes, kale (derive its name from
everywhere)
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Pantothenic acid
serves in its activated form as the cofactor for
coenzyme A (CoA) and the acyl carrier protein (ACP)
first phosphorylated by ATP to 4-
phosphopantothenate
next is the formation of 4-phosphopantetheine by
addition of cysteine and decarboxylation
adenylation by ATP forms dephospho-CoA
phosphorylation to the 3-OH of the ribose generates
CoA (coenzyme A)
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HH
OPO3OH
H H
O
N
NN
N
H2C
O
PO
O
O-
PO O-
O
N
OH
N
O
H
N
O
H
SH
NH2
Coenzyme A
N
S CH3
O
O
H
Acetyl CoA
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Coenzyme A
performs a vital role by transporting acetyl
groups from one substrate to another
the key to this action is the reactive thioester
bond in the acetyl form of CoA the thioester bond is stable enough that it can
survive inside the cell, but unstable enough that
acetyl-CoA can readily transfer the acetyl
group to another molecule
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N
CH3
H3C
H3C
OH
N
CH3
H3C
H3C
O CH3
O
acetyl CoA CoA acetylcholinecholine
Example of an acetylation reaction
Acetylcholine is an important neurotransmitter in
the autonomic nervous system (cholinergic) and in the brain
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Pantothenic acid
Deficiency: rats
graying of hair/fur in black rats
dermatitis
inflammation of nasal mucosa hemorrhage of adrenal cortex
humans
has not been encountered or extremely rare difficult to induce with either synthetic diets
and/or with antagonists (omega-methylpantothenic acid
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Pantothenic acid vague symptoms in human deficiency:
numbness and tingling in feet burning foot fatigue
GIT disturbances
available pharmaceutically as calciumpantothenate (d-isomer) and as racemicmixture
5 - 7 mg/day appear to prevent signs of
deficiency appears to be non-toxic (up to 10-20 gm have
been tolerated)
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Thiamine
N
N
NH2
H3C
CH2 NS
H3C
CH2-CH2-OH
THIAMINE
Vitamin B1; antiberi-beri vitamin; antineuritic factorwas the first water soluble vitamin discovered (Eijkman)
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Thiamine has the odor and flavor of yeast
slowly destroyed by moist heat; more
rapidly destroyed in a basic medium than
in an acid one source: whole cereals and grains; yeast;
organ meat pharmaceutical products use the
hydrochloride or mononitrate salts
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Thiamine
active form is thiamine pyrophosphate (formed
by the action of thiaminediphosphotransferase)
involved in the oxidative decarboxylation ofpyruvic acid and -ketoglutaric acid
involved in the transketolase reactions of thetriose phosphate pathway
also required for nerve function (unrelated tocoenzyme activity)
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Conversion of thiamine to TPP
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Typical reactions catalyzed by
TPP
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Reactions in which thiamine
pyrophosphate is a cofactor
Pyruvate decarboxylase Alcohol fermentation pyruvate to acetaldehyde
Pyruvate dehydrogenase Synthesis of acetyl-CoA
Alpha-ketoglutarate dehydrogenase Citric acid cycle
Transketolase reaction Carbon-fixation reactions of photosynthesis
Acetolactase synthetase Valine, leucine biosynthesis
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Thiamine pyrophosphate
the key portion of this cofactor is the
thiazolium ring with its acidic hydrogen
the hydrogen is removed by the enzymeforming an ylid (anion next to cation)
the anion can then react with carbonyl groupsin such molecules as pyruvate
the pyrophosphate functionality acts as achemical handle which holds the cofactor inplace within the enzyme
thiazolium ring
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N
N
NH2
NS
C
H3C
H
H2CH2C O P
H3C
O
O
O-
P O-
O
O-
thiazolium ring
thiamine pyrophosphate
N
N
NH2
NS
C
H3C
C
H2CH2C O P
H3C
O
O
O-
P O-
O
O-
OH
H3C
H
Hydroxyethyl thiamine pyrophosphate
CH3
ClCH3
Cl
H
O
O-
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N
SH
N
S
acidic hydrogen
O
pyruvate
N
S
CH3
Cl
HO
O-O
N
S
CH3
Cl
OH
- CO2
N
S
CH3 N
S
CH3
Cl
OH
resonance
ylid
H
O
H
H3C H
O
+ ylid
H+
acetaldehyde
Chemical mechanism for
action of B1 in pyruvate
dehydrogenase
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C
CH2OH
C
O
HO H
CH OH
CH2-OPO3H2
C
CH OH
CH OH
CH2-OPO3H2
C
OH
OHH
D-xylulose-5-phosphate D-ribose-5-phosphate
C
C OH
CH OH
CH2-OPO3H2
H OH
C
H
HHO
C
CH2OH
O
C
C OHH
OH
CH2-OPO3H2
+
septulose-7-phosphate
3-phosphoglyceraldeh
transketolase
TPP
Transketolase reaction
Transketolase reaction
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Transketolase reaction
C
CH2OH
C
O
HO H
CH OH
CH2-OPO3H2
D-xylulose-5-phosphate D-erythrose-4-phosphate
C
C OHH
OH
CH2-OPO3H2
+
3-phosphoglyceraldehyd
transketolase
TPP
C
CH OH
C
OH
OHH
CH2-OPO3H2
CH OH
C HHO
C
CH2OH
O
CH OH
CH2-OPO3H2
D-fructose-6-phosphate
These reactions provide a link between the pentose phosphate pathway and
glycolysis
Activity of erythrocyte transketolase is commonly used as an index ofthiamine deficiency
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Thiamine deficiency
earliest symptoms of thiamine deficiencyinclude:
constipation
appetite suppression nausea
mental depression
peripheral neuropathy
fatigue
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Thiamine deficiency (severe)
beri-beri (once associated with whitepolished rice diets and with highly milledwheat diets)
2 clinical types dry beri beri or neuritic beriberi associated with polyneuropathy (depressed peripheral
nerve function, sensory disturbance, loss of reflexes
and motor control and muscle wasting wet beri beri or cardiovacular beriberi
edema, congestive heart failure
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N
N
NS
OH
H3C H3C
CH2-CH2-OH
OXYTHIAMINE
NH2
H3C
N
H3C
CH2-CH2-OH
NEOPYRITHIAMINE
These 2 compounds are potent antithiamine agents which maybe used to induce symptoms of vitamin B1 deficiency in selected
animals. Oxythiamine competitively inhibits thiamine pyrophosphate
and becomes active after phosphorylation; neopyrithiamine
prevents the conversion of thiamine to thiamine pyrophosphate
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Other clinical applications Alcohol neuritis (peripheral neuropathy)
Sharp burning pain in the feet
Deep muscle tenderness with numbness
Coarse tremors, foot drop
Wernickes encephalopathy Results from degeneration of basal ganglia due to
chronic/heavy use of alcohol
Rigidity of extremities
Complete or partial ophthalmoplegia
Sleep disturbances
Nausea and vomiting
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Other clinical applications Korsakoffs syndrome or psychosis
Also a complication of chronic/heavy use of alcohol
Usually follows DTs (delirium tremens)
Memory loss
Delusions Disorientation
Ocular palsies
Combined Wenicke-Korsakoff syndrome
Pregnancy neuritis
Certain gastrointestinal disorders
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Requirement for thiamine
Based on energy needs
0.3 0.6 mg/1000 calories
Increased requirements:
Pregnancy and lactation Eating large amounts of raw sea food (clams)
contain thiaminase
Stress situations (high level of exercise, fever,hyperthyroidism)
Drinking large quantities of tea (containsantagonist)
i i
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Thiamine assay
biologic assay in animals time consuming
and costly (curative or protective)
microbiologic using bacteria which require
thiamine for growth
chemical/fluorescent assay conversion ofthiamine to thiochrome by alkaline ferricyanide
N
N
N
N SH3C
CH 2-CH 2-OH
CH 3THIOCHROME
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Lipoic acid lipoic acid is a co-factor found in pyruvate
dehydrogenase and -ketoglutaratedehydrogenase, two multienzymes involved in-keto acid oxidation
lipoic acid functions to couple acyl grouptransfer and electron transfer during oxidationand decarboxylation of-ketoacids
no evidence exists of a dietary lipoic acidrequirement in humans; therefore it is notconsidered a vitamin
S S SH HS
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S S
H2C
CH2
CH
COOH
SH HS
H2C
CH2
CH
COOH
S S
H2C
CH2
CH
C
N
O
H
CH
NH
C O
lipoic acid, oxidized form lipoic acid, reduced form
lipoamide complex (lipoyl-lysine conjugate)
Lipoic acid exists in 2 forms: a closed-ring disulfide form and
an open-chain reduced form; oxidation-reduction cycles interconvert
these 2 species; lipoic acid exists covalently attached in an amidelinkage with lysine residues on enzymes
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Riboflavin vitamin B2, lactoflavin (ovo, hepato, verdo),
vitamin G a heterocyclic flavin linked to ribose analogous
to the nucleosides in RNA
orange-yellow fluorescent compound found in significant quantities in green leafy
vegetables, milk and meats
heat stable, but easily destroyed by light
recommended intake is related to energy intake(kcal) RDA 1 2 mg/day
dimethylisoalloxazine
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N
N
N
NH 3C
H 3C
O
C
O
H
C
HH
C
H OH
C
H 2C
H OH
H OH
OH
RIBOFLAVIN
y
ring system confers some
degree of planarity to themolecule and also color
(yellow)
Decomposition of riboflavin
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N
N
N
NH3C
H3C
CH3
O
H
O
LUMIFLAVIN
(produced by photochemical cleavage
of riboflavin under alkaline conditions)
N
NH3C
H3C
CH3
O
COOH
+ UREA
NHCH3
NH2H3C
H3C
OH-
OH-
NH
N OO
O
O
H
alloxan
4-amino-1,2-dimethyl
5-methylaminobenzene
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Riboflavin 2 cofactors are involved:
riboflavin phosphate (flavin mononucleotide,FMN)
flavin adenine dinucleotide (FAD)
involved in the metabolism ofcarbohydrates, fats and proteins (flavin
dehydrogenases/flavoproteins) hydrogen carriers in the respiratory
chain
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N
N
N
N O
O
H
H3C
H3C
H2C C C C C O
H
OH
H
OH
H
OH H
H
P O
OH
O
P O
O
OH
CH2
O
N
N
N
N
NH2
OH OH
H H
HH
FLAVINE ADENINE DINUCLEOTIDE
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reduced substance
oxidized substance
FAD
FADH2
cytochrome electron
system (electron transport chain)
dehydrogenases
Riboflavin
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Riboflavin
N
N
N
N O
H
O
H3C
H3C
N
N
N
N O
H
O
H3C
H3C
H
H
FAD (oxidized form) FADH2 (reduced form
hydrogen additionoccurs in 2 steps
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Riboflavin Enzymes utilizing riboflavin cofactors:
NADH dehydrogenase
succinate dehydrogenase
d and l-amino acid oxidases
pyridoxine-5-phosphate oxidase
glutathione reductase
xanthine oxidase In some enzymes, the cofactor is covalently
bonded to an amino acid (dehydrogenases)
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Dehydrogenase reaction
CH2
CO2-
CH2
CO2- FAD FADH2
succinate
dehydrogenase C
CO2-
C
CO2-
H
H
succinate fumarate
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Amino acid oxidases
C
R
NH3+H
CO2-
H2O NH3
FMN FMNH2
R
C O
CO2-
most amino acids (except serine, threonine, basic, and dicarboxylic acids)can be deaminated by L-amino acid oxidases
Xanthine oxidase
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Xanthine oxidase
N
N N
N
OH
H
N
N N
N
OH
H
HO
N
N
N
N
OH
HHO
OH
hypoxanthine xanthine uric acid
xanthine oxidase
Xanthine oxidase is a flavoprotein which also contains Fe and Mo
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Fatty acyl-CoA desaturase
H H
R
H
SCoA
O
R
H
SCoA
OH
FADFADH2
fatty acyl-CoA desaturase
Important step in the biosynthesis of unsaturated fats; thisreaction is actually more complex than shown here and
involves other cofactors, but FAD is a key cofactor for the
enzyme
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Riboflavin deficiency seldom seen in industrialized societies
deficiency when seen: cheilosis (vertical fissure in the lips)
angular stomatitis (craks in the corner of the mouth)
glossitis photophobia
seborrheic dermatitis
normochromic normocytic anemia
usually encountered along with pellagra (niacin deficiency)
newborns treated for hyperbilirubinemia by phototherapy(riboflavin is unstable to light)
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Biotin
NN
S
O
H H
HH
(CH2)4-COOH
BIOTIN
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Biotin an imidazole sulfur containing compound
sometimes referred to as vitamin B7 or vitamin H
widely distributed in foods (liver, kidney, milk,
molasses) a large portion of the daily need of biotin is met by
synthesis by intestinal bacteria
deficiency is usually the result of a defect inutilization rather than simple dietary deficiency
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Biotin
like lipoic acid, biotin is converted to its
coenzyme form (called biotinyllysine or
biocytin) by formation of a covalent
amide bond to the nitrogen of a lysineresidue
like lipoic acid it performs a highlyspecialized function : adds a carboxyl
group to substrates
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Biotin biochemical role: carbon dioxide
fixation
two step process:
1. Binding of CO2 to biotin N-carboxybiotin
2. Transfer of CO2 to a substrate
Activation of biotin requires enzyme,CO2, ATP and Mg
++
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BiotinBiotin-dependent enzymes:
Pyruvate carboxylase (synthesis of oxaloacetate
for gluconeogenesis and replenishment of the
citric acid cycle)
Acetyl CoA carboxylase (fatty acid biosynthesis)
Propionyl-CoA carboxylase
-methylcrotonyl-CoA carboxylase holocarboxylase synthase (multiple carboxylase)
Reactions involving biotin enzymes
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CH3C
O
CO2- CCH2
O
CO2--O2C
pyruvate oxaloacetate
CH3C
O
SCoA CCH2
O
SCoA-O2C
acetyl CoA malonyl CoA
CCH2
O
SCoAH3C
propionyl CoA
CCH
O
CO2--O2C
CH3
methylmalonyl CoA
HCO3- + NH4
+ + ATP CH2N
O
O P OH
OH
O
carbamyl phosphate
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Biotin deficiency:
quite uncommon
can be induced by feeding raw egg white (avidin)
avidin is a protein which binds tighly with biotin (MW
70,000) symptoms are: anorexia, nausea, muscle pain, fine scaly
desquamation of the skin
requirements: 150 200 mcg/day therapeutic use: in babies with infantile
seborrhea (cradle cap) and Leiners disease
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Pyridoxine (vitamin B6)
N
CH2OH
CH2OHHO
H3C
PYRIDOXINE
A pyridine derivative
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N
CHO
CH2OHHO
H3CN
CH2NH2
CH2OHHO
H3C
PYRIDOXAMINEPYRIXOXAL
Other forms of B-6
Collectively, pyridoxine, pyridoxal and pyridoxamine areknown as vitamin B6
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Pyridoxine vitamin B6, rat acrodynia factor,
antidermatitis factor widespread occurrence
pyridoxine: mostly in vegetable products pyridoxal and pyridoxamine: mostly in animal
products
pyridoxine is stable in acid solution, butunstable in neutral or alkaline solutions(destroyed by light)
N
HO
H3C
CH2OH
CH2OH
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pyridoxine
N
HO
H3C
CH2OH
CHO
N
HO
H3C
CH2OH
CH2-NH2
pyridoxal pyridoxamine
N
HO
H3C
CHO
CH2 O P
O
OH
OH
N
HO
H3C
CH2-NH2
CH2 O P
O
OH
OH
pyridoxal phosphate pyridoxamine phosphate
N
HO
H3C
CH2OH
COOH
pyridoxic acid
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Pyridoxal phosphate pyridoxine is converted to pyridoxal phophate
by phosphorylation and oxidation to thealdehyde
pyridoxal phosphate is then attached to the
holoenzyme via a covalent bond to a lysineresidue (a Schiffs base)
the Schiffs base bond is readily broken and
reformed this reversibility is very important in the
biochemical action of this cofactor
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NH
CH2OH
CH2OH
H3C
HO
NH
CH2OPO3
H3C
HO
NH
CH2OPO3
H3C
HO
HO
HN
OH
H
N
Biochemical functions
Able to catalyze the breakdown of amino acids
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Pyridoxal phosphateBiochemical functions:
1. Decarboxylation of amino acids
2. Transaminase reactions
3. Racemization reactions
4. Aldol cleavage reactions
5. Transulfuration reactions
6. Conversion of tryptophan to niacin
7. Conversion of linoleic acid into arachidonicacid (prostaglandin precursor)
8. Formation of sphingolipids
HO
HN H
Lys
HN H
R
O-
O
R
CO2H
NH2
Lys
NH2
ecarboxylation of
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NH
H3C
NH
H3C
HO
N
H
H3C
HO
N
R
H
N
H
H3C
HO
N
R
H
H
N
H
H3C
HO
N
R
H
H
H
H+
N
H
H3C
HO
N
Lys
H
H
R Lys
NH2
H
NH2
resonancestabilization
- CO2
mino acids
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Important transaminases ALT ( alanine aminotransferase)
formerly known as SGPT (serum glutamate
pyruvate transaminase)
alanine + alpha-ketoglutarate = pyruvate +
glutamate
increased serum level in liver injury
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Important transaminases AST (aspartate aminotransferase)
formerly known as SGOT (serum glutamate
oxaloacetate transaminase)
aspartate + alpha-ketoglutarate = oxaloacetate +
glutamate
elevated when heart and/or liver are damaged
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Important decarboxylases
SERINE ETHANOLAMINE ACETYLCHOLINE
TYROSINE DOPA DOPAMINE EPINEPHRINE
TRYPTOPHAN 5-HT SEROTONIN
HISTIDINE HISTAMINE
GLUTAMIC ACID GAMMA AMINOBUTYRIC ACID (GABA)
CYSTEINE CYSTEINE SULFINIC ACID TAURINE
- CO 2
- CO 2
- CO2
- CO 2
- CO 2
- CO 2
Mechanism for transamination
reaction
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N
C
N
C COO-H
R
H
H
N
C
H
N
C
R
COO-
aldimine ketimine
N
H
CH2
NH2
COO-C
O
R
alpha-keto acid
pyridoxamine phosph
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Pyridoxine deficiency:
difficult to produce in humans
may be accomplished artificially with a
pyridoxine antagonist (deoxypyridoxine) symptoms include: nausea and vomiting,
seborrheic dermatitis, depression and
confusion, mucous membrane lesions,peripheral neuritis, anemia
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Pyridoxine antagonists
N
N
NH-NH 2
Hydralazine (antihypertensive)
N
C
O NH
NH2
isoniazid (antitubercular)
O
N
OH2N
H
cycloserine (antitubercular)
CC
CH3 H
COOHHS
CH3 NH2
penicillamine (antirheumatic; Wilson's disease)
Pyridoxine can antagonize the antiparkinsonian use of
L-DOPA
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L-DOPA L-DOPA L-dopamine
L-dopamine
CO 2
Brain
B 6 stimulates
this reaction outsideof the brain
use carbidopa: an inhibitor of DOPA decarboxylase
in combination with DOPA: Sinemet 10/100 or Sinemet 25/250
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Pyridoxine deficiency can be monitored by measuring the level of
xanthurenic acid in the urine
this is related to a decrease in kynureninase
activity (pyridoxal phosphate is the coenzyme)
kynurenine, a breakdown product of
tryptophan is normally converted to kynurenic
acid but in B6 deficiency it is shunted to formxanthurenic acid
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XANTHURENIC ACID
N COOH
OH
OH
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Pyridoxine requirements:
children: 0.5 1.2 mg adults: 2.0 mg
pregnancy: 2.5 mg
Requirement for B6
is proportional to the level ofprotein consumption
therapeutic uses: deficiency
to counterract the effects of antagonists
certain rare forms of anemia
in women taking oral contraceptives (estrogen shiftstryptophan metabolism
COOHDiscovered in 1913 fromyeast; also known as
vitamin B3
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N
NICOTINIC ACID
N
CONH 2
NICOTINAMIDE
1915 1920: Irving Golberg
demonstrated that lack of niacin
causes pellagra
one of the simplest
vitamin; like B6 also
a pyridine derivative
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Oxidation of nicotine yields
i ti i id
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nicotinic acid
N
N
H
N
COOH[OXIDATION]
HNO3
nicotine nicotinic acid
This reaction does not occur in vivo strictly a laboratory
reaction
Ni ti i id
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Nicotinic acid niacin, vitamin B3, niacinamide, antipellagra
vitamin both form are active: the free acid and the
amide sources: organ meat (largest source), fish,
yeast, dried fruit, nuts, cereal grains, somevegetables pellagra-inducing diets: corn meal, corn starch,
sweet potatoes, rice, syrup, pork fat (once a
common diet in southern states amongsharecroppers)
O
NH2
Coenzyme forms
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H
H2C
H
OHOH
H H
ON
NH2
O
H
O P O
O
O-
P
O
O-
O CH2
HH
OHOR
H H
O
N
NN
N
NAD - OXIDATION REACTIONS R = H
NADPH - REDUCTION REACTIONS R = PO3
Two cofactor forms of niacin: NAD and NADP; these cofactors
are not tightly held by the enzyme and may be reused for reactionafter reaction
Bi h i l f ti
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Biochemical function
N
C
NH 2
O
N
C
NH 2
O
HH
NAD +
or NADP +
+ H +
NADH + H +
or NADPH + H +
In the older literature NAD+ is referred to as DPN or coenzyme I
NADP+ is referred to as TPN or coenzyme II
O idi d d d d f
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Oxidized and reduced forms
Sparing action of tryptophan
Tryptophan can substitute for niacin: 60 mg of tryptophan
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TRYPTOPHAN FORMYLKYNURENINE KYNURENINE
3-HYDROXYKYNURENINE3-HYDROXYANTHRANILIC ACID
NICOTINIC ACID
B6-dependent reaction
Tryptophan can substitute for niacin: 60 mg of tryptophanis equivalent to 1 mg of niacin; 60 gm of protein contains 600
mg of tryptophan which then represent 10 mg of niacin
CH
COOH
NH 2
N
CH 2
CH 2
O
CH
COOH
NH 2
N
H
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HC O
Htryptophan
N-formylkynurenine
CH 2
O
CH
COOH
NH 2
NH 2
CH 2
O
CH
COOH
NH 2
NH 2
OH3-hydroxykynurenine kynurenine
alanine
COOH
NH 2
OH
CO 2N
COOH
3-hydroxyanthranilic acid
blocked by deficiency of thiamine
blocked by deficiencyof riboflavin
blocked by deficiency
of pyridoxine
Pellagra
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Pellagra Early stages:
Anorexia
Indigestion
Muscle weakness
Reddened skin
Rough skin
Advanced stages 3 Ds of pellagra: dermatitis, diarrhea, dementia
Clinical uses of nicotinic acid
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Clinical uses of nicotinic acid pellagra symptoms from:
gastric ulcer or carcinoma diarrhea
isoniazid therapy
carcinoid syndrome
Hartnup disease (impairment of tryptophan absorption)
peripheral vasodilator (nicotinic acid ornicotinyl alcohol)
hypolipidemic agent (only nicotinic acid inlarge doses lowers both triglycerides andcholesterol (Niaspan, Nicobid)
Carcinoid syndrome
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a slow growing neoplasm of enterochromaffin cells(ileum, stomach, bronchus)
tryptophan metabolism is altered resulting in excessserotonin synthesis
symptoms include:
facial flushing edema of head and neck
abdomina cramps and diarrhea
asthmatic symptoms
cardiac insufficiency
urinary 5-HIAA (5-hydroxyindole acetic acid) is high (5-HIAA is a metabolite of serotonin; serotonin is derivedfrom tryptophan)
Cautions concerning the use of
nicotinic acid in large doses
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nicotinic acid in large doses as an acid, it can erode gastrointestinal mucosa
leading to ulceration it also causes a depletion of glycogen stores and
fat reserves in skeletal and cardiac muscle
additionally, there is an elevation in bloodglucose and uric acid production
for these reasons, nicotinic therapy is not
recommended for diabetics or persons whosuffer from gout
Ascorbic acid
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vitamin C; anti-scorbutic vitamin (scurvy)
structure is reminiscent of glucose produced in plants from glucose via the uronic
pathway
the enzyme gulonolactone oxidase convertsgulonolactone to ascorbic acid
exists in the enolic and ketonic forms
sources: citrus fruits, tomatoes, green peppers,strawberries, cantaloupe, cabbage, turnips,peas, lettuce and aspargus
ASCORBIC ACID AND
DEHYDROASCOBIC ACID
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DEHYDROASCOBIC ACID
HO
HO
O
O
CH
OH
CH2OH
O
O
O
O
CH
OH
CH2OH
Ascorbic acid
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Biochemical functions:
Production and maintenance of collagen Proline --------hydroxyproline
Lysine -------- hydroxylysine
Mitochondrial electron-transport chain (cytochromeC)
Metabolism of tyrosine
Tyrosine ----- p-hydroxyphenylpyruvic acid---- 2,5-dihydroxyphenylacetic acid (homogentisic acid)
Proline hydoxylase: (collagen formation)
O
O
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Dopamine-beta hydroxylase ( neurotransmitter formation)
N
N
HO
vitamin C; O2
proline hydroxylase
NH2HO
HO
NH2HO
HO
OH
dopamine norepinephrine
dopamine betahydroxylase
O2; Vitamin C
Anti-oxidant properties of vitamin C:
helps prevent damage to cellular proteins and DNA
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OOHO
OH
OHHO
OO
HO
OH
OO
O
Normal metabolic processes in the cell lead to the generation
of reactive oxidizing agents such as superoxide
Superoxide can react with and damage protein and DNA, leadingto cellular changes that can lead to premature aging and cancer
Vitamin C reacts with superoxide, thus preventing this damage
Ascorbic acid
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conversion of folic acid to THFA
hydroxylation reactions of cholesterol to cholic acid hydroxylation of tryptophan to 5-
hydroxytryptophan
regulation of cholesterol biosynthesis in the adrenalgland
aids in the absorption and utilization of iron
antioxidant properties may inhibit formation ofnitrosamines during digestion of protein
Ascorbic acid
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defiency: scurvy
hemorrhage from mucous membranes,mouth and GIT, skin and muscles
gingivitis: swelling, tenderness, redness andulceration of gums
loosening or loss of teeth
swelling of joints
rarefaction of bones and dentine
Ascorbic acid
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requirements:
children: 30 mg
adults: 40 80 mg
pregnancy: 100 mg
therapeutic uses
scurvy
idiopathic methemoglobinemia
questionable use: common cold
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Vitamin B12
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Vitamin B12
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cyanocobalamin (Redisol)
hydroxocobalamin (Alpha redisol)
function
deficiency hematological sequelae
neurological sequelae
Vitamin B12
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synthesized by bacteria only
red in color, levorotatory and stable to heat commercially available either as cyano or
hydroxocobalamin
stored in the liver as the coenzyme absorbed only in the presence of the intrinsic
factor (a glycoprotein released by parietal cells)
transported to tissues via transcobalamin II present in foods such as liver, fish, eggs, milk
absent in vegetables and fruits
Vitamin B12
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by far the most complex vitamin in structure
made up of a planar corrin ring (4 pyrroles) the only vitamin that possesses a metal ion
(cobalt) as part of its structure
the major cofactor form of B12 isadenosylcobalamin or 5-deoxyadenosylcobalamin
small amounts of methylcobalamin also occur(intermediate in methyl transfer reactions)
Vitamin B12
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the corrin ring is similar to the porphyrin ring
system found in hemoglobin except that incorrin 2 of the pyrroles are linked directly(without methylene bridges)
the cobalt is coordinated to the 4 pyrrolenitrogens
one of the axial cobalt ligands is a nitrogen of
the dimethylbenzimidazole group the other axial ligand may be CN, OH, CH3 or
the 5-carbon of a 5-deoxyadenosyl group
N N
CH 3CH 3H2NCOCH 2CH 2
H3C
H2NCOCH 2
CH 2CONH 2
CH 2CH 2CONH 2
Co
CN
H3C
Hcorin nucleus cobalt coordinated
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NNH2NCOCH 2
CH 3
H2C
CH 3
CH 3
CH 2
NH
O
CH 2CONH 2
O
H3C
P
O
O
O
OH
HO
N
N
CH 3
CH 3
CH 3
H
VITAMIN B 12
benzylimidazole
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Vitamin B12
biochemical functions (mediated by
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( ycoenzymes)
mutase reaction (rearrangement reaction methylmalonyl CoA to succinyl CoA (lipid metabolism)
methylation reactions
uracil to thymine homocysteine to methionine
aminoethanol to choline
activation of amino acids for protein synthesis ribonucleotides to deoxyribonucleotides for DNA
synthesis in certain bacteria
Causes of B12
deficiency
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Pernicious anemia (autoimmune gastritis
against parietal cells - loss of intrinsic factor) rarely due dietary deficiency
N2
O/oral contaceptive drugs
intestinal parasite
gastrectomy
chronic gastritis
Schilling test
Diagnosis of B12
deficiency
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Schilling test
distinguishes deficiency caused by perniciousanemia with that caused by malabsorption
compares absorption in radiolabeled B12 with
intrinsic factor and radiolabeled B12 withoutintrinsic factor
in pernicious anemia the B12 with intrinsic factor
will be absorbed while the B12 by itself will not in malabsorption neither will be absorbed
Manifestation of B12 deficiency
macrocytic megaloblastic anemia megaloblasts are abnormal erythroid precursors in
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megaloblasts are abnormal erythroid precursors inbone marrow (most cells die in the bone marrow)
reticulocyte index is low hyperchromic macrocytes appear in blood
anemia reflects impaired DNA synthesis
other cells may be involved (leukopenia,thrombocytopenia
spinal cord degeneration (irreversible)
swelling, demyelination, cell death neurological disease
results from deficient methylmalonyl-CoA mutase
this cannot be treated with folic acid!!
Treatment of B12
deficiency
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use IM cyanocobalamin or hydroxocobalamin
administer daily for 2 - 3 weeks, then every 2 -4 weeks for life
monitor reticulocytosis early to assure
treatment is working (reticulocyte count shouldgo up)
monitor potassium levels to ensure
hypokalemia does not occur due to excessiveRBC synthesis
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Folic acid
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MOA
deficiency
use
drug interactions with folic acid
O COOH
Also known as folacin, vitamin M and pteroylglutamic acid
Widely distributed in leaves (foliage) of plants
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N
N N
N
N
H
C N CH
H
OH
H2N
O COOH
COOH
FOLIC ACID
Chemically composed of pteroic acid (pteridine and PABA)
and glutamic acid
FOLIC ACID
b b d b b th ti d i t t
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absorbed by both active and passive transport
on the average we absorb 50 -200ug per day(about 10 -25% of dietary intake)
storage is in the form of 5-methyl THF (5 -20
mg) found in green vegetable, dietary yeasts, liver,
kidney
bacteria synthesize their own folic acid(dihydropteroate synthetase)
Folic acid
Bi h i l f ti
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Biochemical functions
one carbon fragment transfer (formyl,methyl, hydroxymethyl)
conversion of homocysteine to methionine
conversion of serine to glycine synthesis of thymidylic acid
synthesis of purines (de novo)
histdine metabolism synthesis of glycine
PURINE CARBONS
DERIVED via FOLATE
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N
N N
N
NH2
DNA
N
N N
N
O
DNA
H2N
H
ADENINE (A) GUANINE (G)
BIOCHEMICAL ACTIVATION OF FOLIC ACID
FOLIC ACID 7,8-DIHYDROFOLIC ACID (DHFA)
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TETRAHYDROFOLIC ACID (THFA)N5, N10-METHYLENE
TETRAHYDROFOLIC ACID
N5-FORMYL TETRAHYDROFOLIC ACID (LEUCOVORIN, FOLINIC
ACID, CITROVORUM FACTOR)
OTHER FORMS OF THFA: N 5-METHYL THFA
N 5-FORMIMIDO THFA
N10-FORMYL THFA
N5, N10-METHENYL THFA
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Deficiency of folic acid
I d t i t k
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Inadequate intake
defective absorption (most common) sprue
gastric resection and intestinal disorders
acute and chronic alcoholism
drugs (anticonvulsants and oral contraceptives)
pregnancy pellagra
Deficiency of folic acid
abnormal metabolism of folates
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abnormal metabolism of folates
folic acid antagonists (dihydrofolate reductaseinhibibitors - methotrexate, pyrimethamine,
trimethoprim)
enzyme deficiency vitamin B12 deficiency
oral contraceptives
increased requirement
pregnancy, infancy
METHOTREXATE
H
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N
N N
N
NH2
H2
N
CH2N
CH3
N CH
H
O
(CH2)2-COOH
COOH
METHOTREXATE
Inhibits enzyme dihydrofolate reductase (DHFR) which is
necessary for maintaining pool of reduced folates requiredfor DNA synthesis
METHOTREXATE
also known as amethopterin or MTX
a potent inhibitor of dihydrofolate reductase whicht l th i f f li id t t t h d f li
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catalyzes the conversion of folic acid to tetrahydrofolicacid (THFA)
THFA acts as an acceptor of a one-carbon unit fromeither formate or formaldehyde
5-formyl THFA is also known as folinic acid or thecitrovorum factor (leucovorin)
THFA one-carbon carriers are important in the synthesisof purines, thymine, choline, and other important cellularconstituents
MTX is used in treating acute lymphocytic leukemia inchildren, choriocarcinoma, osteogenic sarcoma,
carcinomas of the head, neck, bladder and testis in lower doses: treatment of psoriasis and rheumatoid
arthritis
N
N
NH 2
CH 2CH 3
H2N Cl
PYRIMETHAMINE
N
N
CH 2
OCH 3
OCH 3
OCH 3
H2N
NH 2
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diaminopyrimidines inhibitors of dihydrofolate reductase
have activity in both bacterial and protozoal organisms more effective if used in combination with another drug
pyrimethamine is more selective for protozoal enzyme thantrimethoprim
used in treatment of malaria and PCP
PYRIMETHAMINE TRIMETHOPRIM(DARAPRIM)
The fat soluble
vitamins
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By
Henry Wormser
Professor of Medicinal Chemistry
Fat soluble vitamins
Vitamins A D K and E are the fat-
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Vitamins A, D, K and E are the fat-
soluble vitamins excessive use of vitamins A and K can
lead to toxicities fat soluble vitamin tend to be stored in
fatty tissues of the body and in the liver
Vitamin A
Exits in 3 forms:
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Exits in 3 forms:
all trans-retinol long chain fatty acyl ester of retinol (main
storage form)
retinal (the active form in the retina)
retinoic acid is also considered to be
physiologically active provitamin A or carotene can be
converted to retinol in vivo
Vitamin A
recommended intakes are expressed in
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pretinol equivalents (RE)
1 RE = 1 mcg of retinol
= 6 mcg of -carorene= 12 mcg other carotenes
older usage expressed activity in USPunits or International units (IU). Thesewere based on biological activity in the
vitamin a-deficient rat (1 IU = 0.3 mcg ofretinol)
Vitamin A contains 5 conjugated double bonds which are
key to some biological actions
Isolated in impure form by McCollum in 1915
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CH3
CH3H3C
CH3
CH2OH
CH3
VITAMIN A (RETINOL)
RDA: 0.7 mg
Vitamin A
Diseases of deficiency:
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Diseases of deficiency:
Nigh blindness and xerophthalmia (dry eye) Skin disorders
Lack of growth Hypervitaminosis:
A serious potential problem (CNS disorders;
birth defects)
CH3CH3
H3C
CH3
H3C CH3
H3C
CH3CH3
CH3
-caroteneliverO2
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CH3CH3
H3C
CH3
CH3
OH
CH3 CH3
H3C
CH3
CH3
O
H
retinal (active form in vision)
CH3CH3
H3C
CH3
CH3
O
COOH
CH3 CH3H3C
CH3
CH3
retinoic acid ("hormonally-active
form")
R
O
vitamin A acetate (R = CH3)
vitamin A palmitate (R = C16H33
retinol (from diet)
Vision and the role of vitamin A
photoreception is the function of 2
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p p
specialized cell types: rods and cones both types of cells contain a
photosensitive compound called opsin
in rod cells opsin is called scotopsin and thereceptor is called rhodopsin or visual purple
rhodopsin is a serpentine receptor imbeddedin the membrane of the rod cell; it is acomplex between scotopsin and 11-cis retinal
Vision and the role of vitamin A
intracellularly, rhodopsin is coupled to a G-
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y, p p
protein called transducin when rhodopsin is exposed to light, it is
bleached releasing the 11-cis-retinal from opsin
absorption of photons by 11-cis-retinal triggersthe conversion to all-trans-retinal (one
important conformational intermediate is
metarhodopsin II); also there is a change in
conformation of the photoreceptor
Vision and the role of vitamin A
these transformations activate a
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phosphodiesterase (which hydrolyzes c-GMP toGMP)
c-GMP is necessary to maintain the Na+
channels in the rods in the open conformation
with a decrease in c-GMP, there occurs aclosure of the Na+ channels, which leads to
hyperpolarization of the rod cells withconcomittant propagation of nerve impulses tothe brain
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H3C CH3
CH3
CH3
H3C
N
N
N
O
H
11-cis
Schiff's base
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H H
lysine chain of opsin
CH3H3C
H3C
CH3
N
CH3
N
NO
H
H
H
1. light
2. isomerization of retinal
3. change in shape of rhodopsin
11-trans retinal
signal transduction nerve impulse
RHODOPSIN
(11-cis retinal + opsin)
Additional role of retinol
retinol also functions in the synthesis of
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certain glycoproteins andmucopolysaccharides necessary for
mucous production and normal growth
regulation
this is accomplished by phosphorylation
of retinol to retinyl phosphate which thenfunctions similarly to dolichol phosphate
Retinoic acid (Retin-A) is important for cellular differentiation;
It controls cellular growth particularly cell growth
Used in the treatment of acne; also used as an anti-wrinkle agent
(Retin A, Retin A micro, Avita, Renova)
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CH3
CH3H3CCH3
COOH
CH3
RETINOIC ACID (RETIN A)
Also used orally to treat acute promyelocytic leukemia (APL)
Product used is Vesanoid (10 mg capsules)
Isotretinoin or accutane is a modification of retinoic acid; it
contains a 13-cis double bond and is orally effective
Used in the treatment of severe acne
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CH3
CH3H3CCH3 CH3
COOH
ISOTRETINOIN (ACCUTANE)
CH3 CH3 CH3
COOH
An aromatic analog of retinoic acid; orally effective and
used in the management and treatment of psoriasis
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CH3O CH3
H3CCOOH
ACITRETIN (SORIATANE)
Etretinate (Tegison)
CH CH CH OC H
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CH3
H3C
CH3O CH3
CH3
CH3
O
OC2H
5
Esterified form of acitretin; also used orally in the
treatment of recalcitrant psoriasis; 10 and 25 mg capsules
Alitretinoin (Panretin)
CH
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CH3H3C
CH3
CH3
CO2H
CH3
9-cis-retinoic acid (Alitretinoin)
Currently used as a 0.1% gel for the topical treatment
of cutaneous lesions in patients with AIDS-related
Kaposi sarcoma
BEXAROTENE (Targretin)
CCH2
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CH3
H3CCH3
H3C CH3
COOH
CH2
Bexarotene (Targretin)
indicated for the treatment of cutaneous
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manifestations of cutaneous T-celllymphoma
usually the patients receiving this drug
have failed to respond to other treatment
protocols
pregnancy (Category X drug)
Adapalene (Differin)
HO2CUsed as a 0.1% gel in the
treatment of acne vulgaris
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OCH3
Adapalene
treatment of acne vulgaris
Tazarotene (Tazorac)
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N C C
S
H3C CH3
EtO2C
Topical treatment of patient with facial acne vulgaris of
mild to moderate severity; gel 0.05%, 0.1%
Vitamin A toxicity
vitamin A is higly toxic when taken inlarge amounts either acutely or
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large amounts either acutely orchronically
may occur with 200 mg (666,000 IU) in
adults or half this amount in children signs include headache, nausea andvomiting, increased cerebrospinal fluid
pressure, blurred vision and bulging ofthe fontanelle in infants
Chemical name Abbreviation Generic name
Vitamin D2 D2 ergocalciferol
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Vitamin D3 D3 Cholecalciferol
25-
hydroxyvitamin
D3
25(OH)D3 calciferol
1,25-dihydroxyvitamin D3
1,25-(OH)3 Calcitriol
24,25-dihydroxy
vitamin D3
24,25(OH)2D3 Secalcifediol
Vitamin D
There are 2 major precursor forms: 7-dehydrocholesterol
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7-dehydrocholesterol
ergosterol
UV irradiation affords cholecalciferol (vitamin
D3) and ergocalciferol (vitamin D2) Discovery:
1890 sunlight prevents rickets
1924 Steanbock and Hess found that irradiating certainfoods produced vitamin D2
1970 hormonally active form of vitamin D discovered
Vitamin D
RDA 20 g (required in minute amounts)
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disease of deficiency: rickets Malformation of bones due to improper bone
mineralization
Hypervitaminosis Toxic dose only 10X higher than the RDA
Causes hypercalcemia can lead to cardiac arrest
vitamin D is not a vitamin (or a cofactor) it isa steroid hormone
HO
OH
CH 37-DEHYDROCHOLESTEROL
PRE-D 3
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CH 2
HO
D 3 (CHOLECALCIFEROL)
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Biological functions
Calcium homeostasis it is critical for the body
to maintain the proper calcium level in the
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to maintain the proper calcium level in the
blood stream
Intestinal calcium absorption: acts as a signal to tell
intestinal cells to take up more calcium from the gut Bone calcium mobilization
Signals osteoclast (bone cells) to release calcium into the
blood stream in response to low calcium levels
Biological functions
Cellular differentiation much less well understood
signal to bone marrow cells to change into other cells
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leukemia cell
1,25(OH)2 vitamin D3
normal white blood cell
derived from bone marrow grows at the proper rate
high levels
Problem: 1,25(OH)2-D3 causes hypercalcemia
Various analogs of vitamin D
Potential use:
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OH
HO
synthetic analog of vitamin D
-anti-cancer agent-immunosuppressive
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CH3
CH3
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CH2
HO OH
H3C
DOXERCALCIFEROL (HECTOROL)
Doxercalciferol (Hectorol)
a synthetic vitamin D analog that undergoes in
vivo metabolic activation to 1-,25-
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dihydroxyvitamin D2
Activation does not require involvement of the
kidneys Used in hyperparathyroidism in patients
undergoing chronic renal dialysis
Initial dose 10 mcg orally 3 times per week
H OH
CH3
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HO
H
OH
PARACALCITOL (ZEMPLAR)
PARICALCITOL (Zemplar)
H OH
CH3
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HO
H
OH
PARACALCITOL (ZEMPLAR)
A synthetic vitamin D analogindicated for the prevention
and treatment of secondary
hyperparathyroidism associated
with chronic renal failure
CH3
H3C OH
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CH2
HO OH
H
CALCIPOTRIENE (DOVONEX)
Calcipotriol (Dovonex)
H3C
OH
a vitamin D derivative approved
f th t t t f i i
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CH2
HO OH
for the treatment of psoriasis.Mechanism of action is unknown.
Receptor affinity is similar to that
of calcitriol, but is less than 1% as
active in regulating calcium
metabolism
Calcipotriene
An analog of vitamin D3 with a modified
id h i t i i 24 OH d
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side-chain containing a 24-OH group anda cyclopropyl group
binds strongly to the D3
receptor on
keratinocytes in skin and it suppresses
their proliferation (used in psoriasis)
has only about 0.5% of the activity of D3on calcium and phosphorus metabolism
Dihydrotachysterol (DHT)
H3CA reduction product of vitamin
D 2
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HO
CH3
D-2Used in the management of
hypoparathyroidism
has only 1/450th the antirachidicactivity of vitamin D-2
Vitamin K
the koagulation vitamin
i t i 2 f
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exists in 2 forms: plant origin: phylloquinone or vit K1 bacterial origin: menaquinones or vit K2
also certain synthetic quinones havevitamin K activity
menadione (vitamin K3) menadiol sodium phosphate (vitamin K4)
O
CH3
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O
CH3
CH3
CH3
CH33
PHYTONADIONE (VITAMIN K 1; PHYLLOQUINONE)
O
CH3
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O
CH3
CH3
CH3
CH3
n = 1 -12
MENAQUINONE (VITAMIN K 2 SERIES)
O
CH3
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O
MENADIONE (VITAMIN K3)
CH2
CO2
CH2 CH2
CHCO
2O
2C
CO2
O2OH
CH3 CH3
O
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3
R
OH
R
O
O
NADH
NAD
WARFARIN & OTHER ANTICOAGULANTS
ANTIVITAMIN K ACTION
OF ORAL ANTICOAGULANTS
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Vitamin E
alpha (E1), beta (E2) and gamma(E3)
tocopherol
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tocopherol sources: plant oils (corn, peanut, wheat
germ), green leafy vegetables, meat, eggs
value resides in the antioxidant
properties of vitamin E (may prevent the
formation of peroxides)
ALPHA TOCOPHEROL
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O
CH3
H3C
HO
CH3
CH3
CH3 CH3
CH3
CH3
ALPHA TOCOPHEROL
Found in a variey of different sources (primarily vegetable fats)
Vitamin E
Estimated requirements: 5 mg/day + 0.6
mg/day of unstaurated fat
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mg/day of unstaurated fat Biological function antioxidant for fatty
acids
Acts like vitamin C; prevents lipid
peroxidation and/or damage to cells by lipid
hydroperoxides
Uses for vitamin E
hemolytic anemia in premature infants,
unresponsive to B12 Fe and folic acid
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unresponsive to B , Fe and folic acid macrocytic megaloblastic anemia seen in
children with severe protein-calorie
malnutrition
Other coenzymesO
O
CH3
CH2CH3O
CH3O
CH C
CH3
CH2 H
10
Serves as entry into the electron-
transport chain
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O
Coenzyme Q (Ubiquinone)
N
N
N
NH2N
H
H OHCHH CH
OH
CH3
OH
Tetrahydrobiopterin
Involved in the conversion ofphenylalanine to tyrosine
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09/12/02