Vitamins

Vitamins are organic substances different in chemical structures and functions,

essential for life, needed in small amounts
.(g mg )
They act as co factors ( co enzymes )Recommended dietary allowance (RDA)Quantity of vitamin recommended for daily )
ingestion to meet essential needs of health
(person
To treat deficiency states, vitamins are given.2 3 times RDA
: Vitamins in nature are present asA)active form e.g. : NAD from niacin
:B)precursor ( provitamin )

:Vitamers
Vitamins in nature present in different forms,e.g. A2 in fresh water fish, and A1 in the other
.animals
Vitamins have no role in energy or .structure tissues

: Vitagens-

.a-Involved in energy and tissues structure

b-Include essential amino acids and essential
.fatty acids

: Source of vitamins
Vitamins cannot be synthesized by -1
:our body except
A- Partially endogenous synthesis (B3 , D )
B- Totally endogenous synthesis ( carotenes
to retinal )
C- Intestinal bacteria ( K2 , Biotin )
.Also from Pharmaceutical synthesis-2
Classification of vitamins according to
:solubility to
:water soluble vitamins -1
: a - B complex
involving : thiamin (B1), Riboflavin (B2) , niacin ( B3 ) ,
pantothenic acid (B5) , pyridoxine (B6 ) , Biotin ( B7 or H ) ,
.folic acid ( B9 ), Cobalamin ( B12 )
b- non B complex : Ascorbic (vit. C)

:fat soluble vitamins:( A, K ,E,D ) -2

: Properties of vitamins
Water soluble
Fat soluble
types-1
:B complex
A,K,E,D
B1 , B2 , B3 , B5 , )
, B6
and ( B7 , B9 , B12)
C
solubility-2 Polar (hydrophilic)
Non polar
(hydrophobic)
absorption-3
Directly in to
Indirectly packed
blood
with chylomicron
and absorbed into
lymph (need bile
salt )
transport-4
No need for
Need carrier
carrier
( lipoproteins)
excretion-5
Excreted in urine
Not excreted in
urine
storage-6 Non stored except : Stored in(1) liver
vit. B12 in liver
.(A, D , E)
Adipose tissue(2)
and muscle (D ,
.E )
defenciency-7
Early (days
Late ( 3 4
weeks )
years )
Except B12
-8 Rare (deficiency is
Common
hypervitaminosis
multiple )
( deficiency is

.singular)

chemical-9
structure

No structural
similarly

Has structural
similarly (contain
Isoprene)

source-10

Same source
(grain) liver
(yeast)

Different source
(animal and
plants)

: Causes of vitamins deficiency

.lack in diet-1
.malabsorption-2

e.g. steatorrhea: leads to absorption of fat soluble

.vitamins
-Intrinsic factor leads to vit. B12 absorption.
3-higher needing in :

-Pregnancy.
-Lactation.
-Stress.
-Smocking.
-Alcohol.

4-Inhibitors:

e.g. :
a)raw fish

inhibitor vit B1

b)raw eggs inhibitor vit Biotin

water soluble vitamins :

(1)Vitamin (B1) : Thiamin also called aneurine
-Sructure : consist of two heterocyclic rings pyridine ring
and Thiazol ring linked by methylene bridge.

RDA 1-1.5 mg / day ( men= 1.2, women 1.1):

Source: whole grains ,watermelon,salamon,meat .

-Active form : Thiamin is rapidly converted to its active

form called pyrophosphate (TPP) or Thiamin diphosphate
(TDP.)
Thiamin di phospho transferace

-Thiamin ( the liver , RBC brain ) ATP Amp

-function of Thiamin (TPP ) or (TDP) :

TPP act as co enzyme of :
1-Oxidative de carboxylation of

a)-pyruvate

keto acids as :

pyruvate dehydrogenase
NAD , FAD , COA ,TPP , Lipoic acid

acetyl COA (in

carbohydrate metabolism )
b) - - Ketoglutarate

K .G dehydrogenase
NAD , FAD , COA ,TPP , Lipoic acid

succinyl COA (in kreb's cycle or citric acid cycle).

c)- Branched chain keto acid de hydrogenase
( metabolism of leucine, isoleucine and valine ).
2-Transketolase in the pentose phosphate pathway
( HMP ).
3-it is essential for nerve conduction and structure.
Deficiency of Thiamin
Causes :
1-Dietary deficiency.
2-Populations using polished rice ( main food ).
3-Renal dialysis and fever.
4-Anta acids and alkalis.
5-raw fish ( contain vitaminase )
( vit. B1 )

destroy thiamin

-Effects of TPP
1)Acumalation of :
-a-pyruvate

lactate lactic acidosis.

- b- ketoglutarate and branched chain amino acids

inhibit Kreb's cycle

ATP

c-pentose sugar.
the following syndromes may result :
A-simple deficiency Beri Beri
Types of Beri Beri:
1-Beri Beri wet : called acute pernicious or shoshin beri
beri

-effect of cardiovascular system (CVS) , edema , heart

failure.
2-Beri Beri dry : effect of peripheral neuropathy.
-other disease e.g. : exhaustion , anorexia , constipation ,
neurological and muscular degeneration.
B-Extreme deficiency : (alcoholism)

inhibitor thiamin

absorption.
1-Wernickes encephalopathy.
Ataxia ( loss of eye coordination ).
2-Korsakoff's psychosis

defective memory

Diagnosis od vit. (B1) :

TPP deficiency is diagnosis by measuring

erythrocyte transketolase
(2)vitamin B2 : (Riboflavin) :
-structure:

It consist of flavin (Iso alloxazine ring ) connected at (N 9 )

and ( C1) of ribitol ( sugar alcohol ).

Note : (B2) contain sugar.

- RAD 1.2 1.7mg.
-Bile salt facilitate absorption
photosensetive : ( decomposes with light ).

Active form :
a-FMN : flavin mono nucleotide contains of : ( flavin ring +
ribose + phosphate ) nucleotide
b-FAD : flavin adenine dinucleotide.
(flavin ring + ribose + phosphate ) nucleotide
(purin ring + ribose + phosphate ) adenenin
nucleotide.

Function of Riboflavin :
- Essential for energy :

1-FMN and FAD are hydrogen carries ( at N1 and N10 of

flavin ring)
in oxidation reduction reactions ( mainly oxidation )
FAD FADH2 ETC

2ATP

FMN FMNH2
2-FMN co enzyme of :
a-L. amino acid oxidase.
b-NADH dehydrogenase in Elctron Transport Chain (E.T.C).
3-FAD co enzyme of :
a-xanthin oxidase and glutathione reductase.
b-succinate dehydrogenase (Kreb's cycle ).
c-Acetyl COA dehydrogenase in fatty acid oxidation.
d-pyruvate dehydrogenase in carbohydrate metabolism.
4-Flavoproteins contain one or more metal e.g.
(molybdenum and iron): metallo flavoprotein.

Deficiency:

-New borns with hyperilirubinemia treated by photo

theraby leads to riboflavin deficiencies.
-Thyroid hormones.
- ACTH.
- Drugs as chlorpromazine, alcohol.

- (Riboflavinosis ) lead to :
- Smooth red tongue ( Glossitis).
-Angular stomatitis.
- Inflammation of GI tract ( Seborrhea).
- sore throat
-cracks and redness at corners of mouth ( Stomatitis )
- sensitive to sun .

Diagnosis : by measuring the activity of

glutathione reductase.

: Niacin Vit(B3) -3

: Structure : priding ring

Forms of

Niacin : Nicotinic acid , Nicotin amide

Nicotinic acid decreases of plasma cholesterol and .inhibit hormone sensitive lipase
.Nicotinamide produce active form

: Source
. Vit B3 synthesized from tryptophan
In the presence of vit (B6)
tryptophan 1mg niacin (B3) ( 60mg)
Yeast , coffe , tea , liver , meat
.RAD:

16 -34 mg

:Active form
NAD+nicotin amide adenine dinucleotide
.NADP nicotinamide adenine dinucleotide phosphate

: Synthesis

Diet
Nicotinic acid

Nicotinamide

Nicotinic acid mono nucleotide

NADP+
+
NAD

:Function
1- NAD and NADP are hydrogen carriers { carry hydride (H - )
on C4 , N1 , and free proton ( H+ ) is generated } In the
oxidation reduction reactions.
C4 accept hydrogen atom.
N1a accept electron only.
+

NAD+ + H2

+ H2

NADP+ + H2
NADH

NADH + H+
NADPH + H+

ETC

3 ATP

NAD+ is coenzyme e for dehydrogenase ( oxidation ) as:

- Glyceraldehyde 3- p- dehydrogenase.
- Pyruvate dehydrogenase complex.
- 3 - Hydroxyl acyl coA dehydrogenase
- Lactate dehydrogenase.
- 3- Hydroxy acyl coA dehydrogenase.

NADP+ :
- Hmp shunt

co enzyme reductases ( reductions ) as :

g-6-pdehhedrogense

6-phosphoglyconate dehydrogenase
Iso citrate dehydrogenase.Malate dehydrogenase .Cholesterol , fatty acid , steroid ,synthesis .Glutathion reductase NAD+ is the source of ADP riposylation of protein and -2
.nucleoproteins in DNA synthesis
Used in more than 200 reaction -

:De feciency
Pellagra 5days dermatitis, Diarrhea, dementia , deplession,
.death
.Causes: B3 , B6,tryptophan
:Endemic in populations using .Maize (corn)no tryptophan and vita B3 is bounded (un free) - sorghumcontain
high concentration of
lucin
inhibit
ofconversation of tryptophan to B3 .
- Drugs as isoniazid( tuberculosis ).
- cancer tumor of liver enterochromaffin cells. ( tryp
serotonin ).

- Toxicity of niacin:
- Hartnup disease:
Gentic defect in intestinal absorption of tryptophan

High dose of B3 flushing , piuritis, a ggrevate asthma.

-Intake
>
500mg-day
liver
Vit B5 ( pentoic acid ) :
Structure : pentoic acid + - alanine pantoic acid
+
Pentoicacid .bdihydroxy B- dimethyl
b- alanine deriver froms:

damage

aspartwte decar boxylation (bacteria)

cy stein (human)
active form:
A C P (acyi carrier protein )largest coenzyme
C0A S H
Function:
Acp formed of u- phosphor pantothe in att ached to oh of serine
of protein
It is acom pon ent of fatty acid syn the sis complex

COA-SHact as acy (fa)

Group carrier by the active center (sh)
Formed ofthio ethanamine
B- alanine , pentoc acid and pyropho sphate and Amp syn the sis
of COA SH require 3a
AC pand COA CONTAIN (SH) thi group

Stnj the sis

(SH)cyster
co2
thio ethanami cs
pan to the nic acid
4- phosphopan to then acid ATPADP
4ACP

phosphopan to thein (SH) ac.p PROTEI

ATP

ATP

ADP

PPI
COA -SH

De fercincy:
Vare
Burning foot syndrome in

Tingling hnds , fatique n ausea , I rritability

4- B6: pyridine,pyridoyal
Pyridoyamie
Structure pyridiner ring
RAD1.6 - 2.2mg
Plasem a 4 - 9 mg-L
Muscie phos pho rylase has 70-80degrees of total body B6
Source : meat ,liver
M a ckerel , bananas , vegetubles , milk , fish
I thas three forms
- Pyridexin(alcohol)
- Pyridexal(aldehyde)ATPADPPYRODOYAL- P(PL)
Pyridoxaminecamine kinase(zn2+)pyrodoxamin-1
pyridoxinoxidation pyrodoxaltrans
aminationpyridoxmine.

Active from: pyridoxal phosphate(plp)

Function:
1- Energy
2- Amino acid smetabolism
a- Trans aminationi CCO- trans aminases)
- The aldehyde group of plp from sciffbase with the amino
group of amino acid facilitate thechanges in the other
groups .
- The aldehyde group of plp reuct with trans aminase to from
schiffbase(with amino group of lysine)and ionic bond(with the
nh3+)
Trans amination cofactor pyridoxal-p
Pyridoxaminet
Corboxylation: (cadecarboxylas)

Glutamate co2gaba (gama amino butericacid )

Histidine--co2histmine
DOPACO2dopamine
______________________________________________________________

Deficiceincy
1-cuses
a- Pregnancy and lactation
b- Long term use of contraceptive
c- Alcoholics
d- drugsI N H ,cycloserine and pencil amine
2-mani festations
a- 6TTanorexia,nausea,vomiting,inea, ly pregnancy.
b- neurologicalperipheral neuritis
c- hema to logical sidrroblastic anemia
d- hormone depedant can cer (breast,vterus)
abnormalities of try pto phan and methionine
metaholism
________________________________________________________

To xi city
2-6gm - day for 2-months or more cirrversible nerve
damage) : syp toms
Gait a bnormality tingling in extremities, numbness
B7 - biotin
Structure:
2-fused rings Imidazol ring
Thiophene ring (with valericacid side chain)
Function:
Biotin is a coenzyme for all (carboxylase enzymes cco 2
fixation)
Except (amino imidazole riposy 1-5-p carboxylase
Indiet biocytin (biotin + lysine)

The carproxylation reaction require

1-carboxylase
2-biotin
3-HCO3 a sorce of CO2
4-atp AND MG+2
NOTE : biotin can be syn the sis by in testinal bacteria
Carboxylase enzyme formed of 3 sub units:
Biotin binding protein firmly bounded to lysine .
Biotin carboxylase (attached CO2 from biotinto
substrate )
N.B: Reactive in termediate is n- carboxy biocytin.

Causes.
Ingestion of large amount of raw eggs (contain avidin)
prevent bioyin absorption.
Antibiotics:
Defe ciencg of holcarboyylase
Synthesis immunodefeciency in childrens
Vit B12
Structure:
Consist of carrin ring +cobalt (trace elemen)
Carrin ring tetrapyrrol linked by :
A 3 methenylbrides
B 1- H bond

Cobalt is linked to

to

1- 4N of pyrroll
2- Neucleotide (5,6,dimethgl-benzimidazole)
3- Side group as:
a- ohhydroyl cobalamin
b- ch3methylcobalamin
c- 5-deoxy adenosineDeoxy adenosinedeoxy adenosylcombalamin'
d- CNcyanocbal amin(synthetic)
Source:anmimals source :
(liver, eggs) and it is abscent in plants .
Can be synthesized in human colon by microorg
anisms(bacteria)
RAD 2-4-mg-day
__________________________________________

Absorption:
Vit B12 bind to salivary cobalophin
(protect B12 from gastric acid iby)at the duodenum B12 binds
To internsic factor (protein from parieta1 cell sof stomach)vita
B12 iFF complex recognized byi lial cell sup take of
cobalamine cweakly bound )in the liver B12 bind to trans
cobal amin(I.Firmly bound)
Activeform:
Methyl cobal amin (cytosol) cofactor of methionine synthesis
Methionine sqnthase

Homocysteln

lipotropic

n-5 methy THFTHFDNA synthesis (purine and thy midine synthesis)

Deoxy adenosyl-cobalamine (cmibochondoria)

Cofacbor of methy-malonyl
Mutase and leacine amino mutase
Methgl- malonate - COAsyccingl.COA
Deficiency
1)vaie and main feta tions
Appeais agter years as it is stored in the liver for years (6 years)
Causes :
-vegeterians
-inaugurate absorption
1 gastre ctomy
Au to immune disease of parietal cell no if perni ceous animia

3 Terminal I lealdisease
4-Dragsantibiotlcs neogcin alcoholics < coiichicin
5-tapewarms
6-pancreatic insufficiency
Man Festations
-Folate trap and no methionine
1 hematological pancytopenia
-pan cytopenia
anemia cmegalloblastic
leu kopenia
throm bocytopenia
-Howocgsteinurea
-metyhl- malonic acidurea
2 nervous subacte progressive
Dcmyeli nation of nerve
Fibers lat column (motor)
And post column (sensory)
(due to accumulation of
Methgl-malongl-Coa

Folic acid (folate)

- Pterogl glutamate
- Structure
- -itconsist of pteric acid pteridlne ring paba
- folic acid in diet is polyglutam ated for
- hgdorly sed by glutam ate carboxyl peptidase
- monoglutam atedfrom easily absorped

- Active form: intestinal cell

-

Folatereductase
DHFreductase
Folicid acid DHF
NADPH+H NADP NADPH+H NADP+

THF (activr from )

- THF = Tetra hydor folate
N.B- methotrexate (chemotherapy ) inhibit DHF reductase
- sulfon amide as trimethoprime
(Antibiotic ) PBA analogue

Sources
Green leafly vegetables legumes orange sunflowerseeds
fruits
(citrus,liver (pentag lutamgl conjugate yest
RAD =200MY
-Function :
THF is acarrier of activated of carbon units (on N5, N10) as
Methyl / methylene (precursi) /methenyl/ formyl /formimino
All of the carbon units are interconvertable except N5
methyl THF which is the major circulating from .
N5 from THF n10 formyl THF is the most stable forms
Note: n5 formyl THF (folinic acid)

Sources of carbon units

1- Carbon of glucaine
2- B- carbon of serine
3- Tryptophan N10 formgl THF
4- HistidineN5 folmimino THF
Remember that
N5
No10
N5,N10

-methylene
-methyl
formyl
-metheneyl
-Frmgl
-Formation

Uses of carbon units :

1- N5,N10 methylen THF @dump Tmp
b- Gly in serine
2- N5,N10 meth engl THF C8 of purine
3- N10 formyl THF C2 of purine
4- N5 methyl THF Homcysteinmethionin
Deficiency :
( alcolics , pregnancy , anticonvulsant )
1 pancytopenia anemia (megallobla
leukopenia
thrombocyte toxemia
Anemia C aused by folic acid not associated with
nervous
-mani festations and treated by giving folate
2 Homocy stein urea risk of atherosci erosis ,
thrombosis and hyp prten sion.
3 risk of neural ube defedt as (spina bifide)
: 400 Mg ay of folate is given to the pregnant women
Before and during pregnancy risk of neural tubedef

Hydroxyl lases require cupper dopamin

1 hydroxglase
2peptiday glycin hydroxyl
3 phpphydroxylase
iron proly and ysy hydroxyl
2 Aspartate-B- hydioxyla
3 trimeth yl lysine and butyl rob
detain
Source mainly plants (vegerables , fruits
It is the most required by human (60mg /day)
- -Defeciency :
Causes : cooking and canning .
(vitc is the most unstable vit
- Maini festations s curvy 1 gum bleeding ( soft and swollen )
2 deelay wound h healing and tooth erupti
3 petechia (Bruises )
4 bone fracture
5 anemia ciron deficiency anemia)
6 hypecholester olanemia