Transcript Water – soluble Vitamins- lecture slides ppt.pps

Water – soluble Vitamins
Water – soluble Vitamins
Vitamins : are
– chemically unrelated organic compounds
– cannot be synthesized by humans
– must be supplied by the diet.
water-soluble Vitamins;
–
–
–
–
–
folic acid
ascorbic acid (C)
Thiamine (B1)
Riboflavin (B2)
pantothenic acid
- cobalamin (B12)
- pyridoxine (B6)
- niacin (B3)
- biotin
Many of the water-soluble vitamins are precursors
of coenzymes for the enzymes of intermediary
metabolism.
FOLIC ACID (Folate)
Plays a key role in one-carbon metabolism.
Essential for the biosynthesis of AA, purines, thymine...etc.
Folic acid deficiency is the most common vitamin deficiency
in the United States, particularly among pregnant women
and alcoholics.
Function of Folic acid
Serine, glycine, and histidine  one-carbon fragments
to Tetrahydrofolate  transfers them to intermediates
in the synthesis of amino acids, purines, and thymine a pyrimidine found in DNA.
Nutritional
anemias
Nutritional anemias : classified
according to RBC size or MCV.
a) Microcytic anemia (MCV<80 m3):
•
•
caused by lack of iron
the most common form of
nutritional anemia.
b) Macrocytic anemias (MCV>100 m3):
• due to folic acid or vit B12 def.
• called megaloblastic because folic
acid or vit B12 def. accumulation of
large, immature red cell precursors
(megaloblasts) in the bone marrow.
• Low blood [Hb]  O2 transport
Anemia
Folate and anemia:
increased demand:
• Pregnancy
• Lactation
Causes of  serum
folate levels
poor absorption:
• pathology of gut
• Alcoholism
• ttt with : Methotrexate
(DHF reductase inhibitor)
folate-free diet
Results of
folic acid deficiency
megaloblastic anemia due to
 synthesis of purines and thymidine 
 DNA synthesis and cell division.
– The causes of the megaloblastic anemia should be evaluated prior to
instituting therapy because vitamin B12 deficiency  indirectly causes
this disorder.
Folate and neural tube defects in the fetus:
Spina bifida and anencephaly, the most common neural
tube defects.
affect ~ 4000 pregnancies in USA / year.
Folic acid supplementation before conception and during
the first trimester ( 0.4 mg/day)   the risk of neural tube
defects in the fetus.
The U.S. FDA has authorized the addition of folic acid to
enriched grain products, ( about 0.1 mg day).
This supplementation will allow ~ 50% of all reproductiveaged women to receive 0.4 mg of folate from all sources.
Folic acid intake should not exceed ~ 1 mg/day to avoid
misdiagnosis of vit B12 deficiency.
COBALAMIN (VITAMIN B12)
• Required in humans for
2 essential enzymatic
reactions:
A) Methionine synthesis
B) isomerization of
methylmalonyl CoA
(produced during the
degradation of some AA,
and fatty acids with odd
numbers of carbon atoms)
Deficiency of B12 
accumulation of
abnormal fatty acids 
incorporated into cell
membranes, including
nervous system 
neurologic
manifestations .
A. Structure of cobalamin and its coenzyme forms
Coordination
bonds
cyanide is
replaced by
CH3 group
cyanide is replaced with
5-deoxyadenosine
differs from the porphyrins in
that two of the pyrrole rings are
linked directly rather than
through a CH3 bridge
Cobalt is held in the center of the corrin
ring by four coordination bonds from the
nitrogens of the pyrrole groups
Distribution of vit B12 :
Vitamin B12 is synthesized only by
microorganisms.
It is not present in plants.
Animals obtain the vitamin preformed from:
– their natural bacterial flora.
– by eating foods derived from other animals.
B12 is present in:
• liver
• whole milk
• eggs
• oysters
• fresh shrimp
• chicken
Folate trap hypothesis :
B12 deficiency affects:
• the erythropoietic tissue of bone marrow
• the mucosal cells of the intestine
need both N5-N10-methylene &
N10- formyl forms of THF for
nucleotides synthesis required
for DNA replication.
• In B12 deficiency, the N3-methyl form of tetrahydrofolate is
not efficiently used.
• Methylated form of THF cannot be converted directly to
other forms  accumulation of he N5-methyl form & 
of other forms.
B12 deficiency is hypothesized to  deficiency of the
THF forms needed in purine and thymine synthesis, 
megaloblastic anemia.
Clinical indications for vitamin B12
Unlike other water-sol Vitamins, significant amounts of
vitamin B12 (4 - 5 mg) are stored in the body.
SO,
Development of clinical symptoms of B12 deficiency take
several years in individuals with partial or total gastrectomy
(intrinsic factor-deficient with loss of B12 absorption).
Pernicious anemia:
• Vitamin B12 deficiency is
rarely due to dietary
insufficiency.
• Deficiencies are more common
in patients with intestinal
malabsorption of the vitamin 
pernicious anemia.
 Autoimmune destruction of
the gastric parietal cells  
synthesis of the intrinsic factor
(Glycoprotein).
 Normally, dietary vitamin B12 binds to intrinsic factor in the intestine
 cobalamin - intrinsic factor complex  travels through the gut 
binds to specific receptors on the surface of mucosal cells of the ileum
 transported into the mucosal cell  general circulation  carried by
B12-binding proteins.
– Lack of intrinsic factor  prevents vitamin B12
absorption  pernicious anemia.
– Neuropsychiatric symptoms develops later .
– CNS symptoms may occur in the absence of anemia.
– The CNS effects are irreversible.
Treatment
– by giving high-dose B12 orally, or cyanocobalamin IM.
– Therapy must be continued throughout the lives of
patients with pernicious anemia.
Folic acid administration alone reverses the hematologic abnormality 
masks the B12 deficiency  severe neurologic dysfunction and pathology;
therefore, megaloblastic anemia should be treated with a combination of
folate and vitamin B12
ASCORBIC ACID (VITAMIN C)
The active form of vitamin C is ascorbic acid.
The main function is as a reducing agent in several different reactions.
Vitamin C has an essential role as a coenzyme in hydroxylation reactions,
e.g, hydroxylation of prolyl- and lysyl-residues of collagen .
Vitamin C is required for:
– maintenance of normal connective tissue
– wound healing
– facilitates the absorption of dietary iron from the intestine.
Deficiency of ascorbic acid:
Deficiency of ascorbic acid  deficiency in the
hydroxylation of collagen  defective connective tissue
 scurvy.
Scurvy
 sore
 spongy gums
 loose teeth
 fragile blood vessels
 swollen joints
 anemia
Prevention of chronic
disease:
Vitamin C , vitamin E and -carotene are known as
antioxidants.
Consumption of food or supplements rich in these
compounds   Coronary heart disease and certain
cancers.
Supplementation with the isolated antioxidants have low
beneficial effects.
PYRIDOXINE (VITAMIN B6)
Pyridoxine
pyridoxal
pyridoxamine,
Derivatives
of pyridine.
 They differ only in the nature of the
functional group attached to the ring
in animal
foods
All three compounds can serve as
precursors of the biologically
active coenzyme, pyridoxal
phosphate.
Pyridoxal phosphate functions as a
coenzyme  catalyze reactions
involving amino acids
primarily in plants
Reaction type
Example
Oxaloacetate + glutamate 
Transamination
aspartate + α-ketoglutarate
Deamination
Serine  pyruvate + NH3
Decarboxylation Histidine  histamine + CO2
Condensation
Glycine + succinyl CoA δaminolevulinic acid
Clinical indications for pyridoxine:
Isoniazid (isonicotinic acid hydrazide), [a drug frequently
used to treat TB]  B6 deficiency by forming an inactive
derivative with pyridoxal phosphate.
Dietary supplementation with B6 is important with
isoniazide treatment.
Dietary deficiencies in pyridoxine are rare but observed in:
– newborn infants fed formulas low in vitamin B6
– women taking oral contraceptives
– alcoholics.
intakes of greater than 2 g/day 
Toxicity of
pyridoxine:
Neurologic symptoms
Substantial improvement, but not
complete recovery, occurs when the
vitamin is discontinued
THIAMINE (VITAMIN B1)
Thiamine
pyrophosphate (TPP) is:
the biologically active
form of the vitamin,
formed by the
transfer of a
pyrophosphate group
from ATP to thiamine
PP from ATP
Clinical indications for thiamine:
Thiamine pyrophosphate (TPP) serves
as a coenzyme in :
the formation or degradation of
α-ketols by transketolase
the oxidative decarboxylation
of pyruvate and α -keto acids
Important for CNS
Thiamine deficiency:
  activity of dehydrogenase reactions
  ATP  impaired cellular function.
Thiamine deficiency is diagnosed by:
 erythrocyte transketolase activity
observed on addition of TPP.
Beri
beri:
– Severe thiamine-deficiency syndrome.
– Found in areas where polished rice is the major
component of the diet.
– Rapid onset in nursing infants whose mothers are
deficient in thiamine.
infantile beriberi
Adult beriberi
– tachycardia
– vomiting
– convulsions
– death (if untreated)
- dry skin
- irritability
- disorderly thinking
- progressive paralysis
Wernicke-Korsakoff
syndrome:
– In the United States, thiamine deficiency, which is
seen primarily with chronic alcoholism, is due to:
dietary insufficiency.
impaired intestinal absorption of the vitamin.
Some alcoholics
Wernicke - Korsakoff
syndrome
- apathy,
- loss of memory
- rhythmical to-and-fro motion of the eyeballs
NIACIN
Niacin, or nicotinic acid, is a substituted pyridine derivative
The biologically active coenzyme forms are:
1. nicotinamide adenine dinucleotide (NAD) and its phosphorylated
derivative,
2. nicotinamide adenine dinucleotide phosphate (NADP)
Nicotinamide, a derivative of nicotinic acid that contains an
amide instead of a carboxyl group, deaminated in the
body So it is nutritionally equivalent to nicotinic acid.
NAD+ and NADP+
serve as coenzymes in
oxidation-reduction
reactions in which the
coenzyme undergoes
reduction of the pyridine
ring by accepting a
hydride ion (hydrogen
atom plus one electron)
The reduced forms:
NAD+  NADH
NADP+  NADPH
A. Distribution of niacin
Sources
unrefined and enriched grains and cereals
milk
lean meats especially liver.
Limited quantities of niacin can also be
obtained from metabolism of tryptophan.
60 mg tryptophan  1 mg nicotinic acid
tryptophan is metabolized to niacin only when
there is a relative abundance of the amino acid
B. Clinical indications for niacin :
Deficiency of niacin
Pellagra
if untreated
Dermatitis
Diarrhea
Dementia
Death
Treatment of hyperlipidemia:
Niacin
(at doses of 1.5 g /day or 100 times the RDA)
inhibits lipolysis in adipose tissue
( the primary producer of circulating free fatty acids).
 triacylglycerol synthesis in liver
 VLDL and LDL
Niacin is particularly useful in the treatment of type lIb
hyperlipoproteinemia (in which  VLDL & LDL ).
RIBOFLAVIN (VITAMIN B2)
(FMN)
(FAD)
FMN & FAD are:
the 2 biologically active forms.
formed by transfer of AMP from ATP  FMN.
capable of reversibly accepting 2 H atoms  FMNH2 or FADH2
bound tightly - sometimes covalently - to flavoenzymes that catalyze
the oxidation or reduction of a substrate.
• dermatitis
Deficienc
y
• cheilosis (fissuring at the corners of the mouth),
• glossitis (the tongue appearing smooth & purplish).
BIOTIN
A coenzyme in
carboxylation reactions,
( serves as a carrier of activated
CO2 ).
Covalently bound to the
-amino groups of lysine
residues of biotindependent enzymes.
Required by all
organisms.
Can only be synthesized
by: bacteria, yeasts,
molds, algae, and some
plant species.
Acetyl-CoA carboxylase:
catalyzes the binding of HCO3- to acetylCoA to form malonyl-CoA required for the
synthesis of fatty acids.
Pyruvate carboxylase:
in gluconeogenesis  formation of
glucose from amino acids and fats.
Each Carboxylase
catalyzes an essential
metabolic reaction:
Methylorotonyl-CoA carboxylase:
in the metabolism of leucine, an essential
amino acid.
Propionyl-CoA carboxylase:
in the metabolism of amino acids,
cholesterol, and odd chain fatty acids
(fatty acids with an odd number of carbon
molecules)
Biotin deficiency
Human requirement
for dietary biotin in:
very rare.
does not occur naturally.
the vitamin is widely distributed
in food.
in humans, big percentage is
supplied by intestinal bacteria.
• prolonged IV feeding without
biotin supplementation.
• consumption of raw egg white
for a prolonged period .
Addition of
raw egg-white
to the diet
as a source
of protein
symptoms
of biotin
deficiency
Neurologic
symptoms
in adults
• dermatitis
• glossitis
• loss of appetite
• loss of hair
• nausea
• scaly red rash around
the eyes, nose, mouth,
and genital area.
depression
lethargy
hallucination
numbness
tingling of extremities.
Raw egg white contains a glycoprotein, avidin  tightly binds biotin 
prevents its absorption from the intestine.
Cooking egg white  denatures avidin renders it digestable 
unable to prevent the absorption of dietary biotin.
With a normal diet, 20 raw eggs / day would be required
to induce a deficiency syndrome.
The Adequate Intake (AI): average intakes of biotin (35
mcg to 60 mcg/day) are meeting the dietary requirement.
Uses:
In larger doses, biotin is used to treat inborn errors of
metabolism such as biotinidase deficiency.
Biotin is incorporated into almost all nutritionally complete
dietary supplements and infant formulas.
PANTOTHENIC ACID
Sources:
• Eggs
• Liver
• Yeast
A component of
coenzyme A, which
functions in the transfer of
acyl groups
Coenzyme A contains a
thiol group that carries acyl
compounds as activated
thiol esters.
such structures are
succinyl CoA, fatty acyl
C0A, and acetyl CoA.
Deficiency
• Is not well characterized
in humans,
• No RDA is established.
Pantothenic acid is also a component of fatty acid synthase .