WATER-SOLUBLE VITAMINS

By

Saleh Sharif
 Vitamin B1
(Function)
§ Thiamin has a central role in energy-yielding metabolism, and
especially the metabolism of carbohydrate
§ Thiamin diphosphate is the active form
§ is the coenzyme for three multi-enzyme complexes that
catalyze oxidative decarboxylation reactions:
1. pyruvate dehydrogenase in carbohydrate metabolism;
2. α-ketoglutarate dehydrogenase in the citric acid cycle
3. branched-chain keto-acid dehydrogenase involved in the
metabolism of leucine, isoleucine, and valine
§ the coenzyme for transketolase, in the pentose phosphate
pathway
 Vitamin B1
(Deficiency)
§ Thiamin deficiency can result in three distinct syndromes:
1. a chronic peripheral neuritis,
2. beriberi, which may or may not be associated with heart
failure and edema
3. Wernicke’s encephalopathy with Korsakoff’s psychosis,
which is associated especially with alcohol and drug abuse
§ results in increased plasma concentrations of lactate and
pyruvate, which may cause life-threatening lactic acidosis.
 Vitamin B2
(Function)
§ Riboflavin fulfills its role in metabolism as the coenzymes
flavin mononucleotide (FMN) and flavin adenine
dinucleotide (FAD)
§ FMN is formed by ATP-dependent phosphorylation of
riboflavin
§ FAD is synthesized by further reaction of FMN with ATP in
which its AMP moiety is transferred to the FMN
§ The main dietary sources of riboflavin are milk and dairy
products.
§ Flavin coenzymes are electron carriers in Oxidoreduction
reactions
 Vitamin B2
(Deficiency)
§ itis not fatal as there is very efficient conservation of tissue
riboflavin
§ Riboflavin deficiency is characterized by cheilosis, lingual
desquamation and a seborrheic dermatitis
 Vitamin B3
(Concepts)
§ Niacin is not strictly a vitamin since it can be synthesized in the
body from the essential amino acid tryptophan
§ Two compounds, nicotinic acid and nicotinamide, have the
biologic activity of niacin
 Vitamin B3
(Function)
§ Function is as the nicotinamide ring of the coenzymes NAD
and NADP in oxidation-reduction reactions
§ NAD is the source of ADP-ribose for the ADP-ribosylation of
proteins
§ And polyADP-ribosylation of nucleoproteins involved in the
DNA repair mechanism
 Vitamin B3
(Deficiency)
§ Pellagra is caused by deficiency of Tryptophan & Niacin
§ Pellagra is characterized by a photosensitive dermatitis,
dementia, diarrhea, and, if untreated, death
§ deficiency of riboflavin or vitamin B6 cause pellagra,
because both of which are required for synthesis of
nicotinamide from tryptophan
§ twice as many women as men are affected, as a result of
inhibition of tryptophan metabolism by estrogen metabolites
§ Hartnup disease is a rare genetic condition in which there is
a defect of the membrane transport mechanism for tryptophan
 Vitamin B3
(Deficiency)
§ Carcinoid syndrome there is metastasis of a primary liver
tumor of enterochromaffin cells which synthesize 5-
hydroxytryptamine
§ Overproduction of 5-hydroxytryptamine causes pellagra
 Vitamin B6
(Concepts)
§ Six compounds have vitamin B6 activity: pyridoxine,
pyridoxal, pyridoxamine, and their 5′- phosphates
§ The active coenzyme is pyridoxal 5′-phosphate
§ Approximately 80% of the body’s total vitamin B6 is present as
pyridoxal phosphate in muscle, mostly associated with
glycogen phosphorylase
 Vitamin B6
(Function)
§ Pyridoxal phosphate is a coenzyme for many enzymes
involved in amino acid metabolism, especially in
transamination and decarboxylation
§ the cofactor of glycogen phosphorylase
§ vitamin B6 is important in steroid hormone action where it
removes the hormone-receptor complex from DNA binding,
terminating the action of the hormones.
 Vitamin B6
(Deficiency)
§ clinical deficiency disease is rare
§ Moderate deficiency results in abnormalities of tryptophan
and methionine metabolism
§ Increased sensitivity to steroid hormone action may be
important in the development of hormone-dependent cancer
of the breast, uterus, and prostate, and vitamin B6 status may
affect the prognosis
 Vitamin B12
(Concepts)
§ The term “vitamin B12” is used as a generic descriptor for the
cobalamins
§ is found only in foods of animal origin, there being no plant
sources of this vitamin
§ This means that strict vegetarians (vegans) are at risk of
developing B12 deficiency
 Vitamin B12
(Absorption)
§ Vitamin B12 is absorbed bound to intrinsic factor
§ A small glycoprotein secreted by the parietal cells of the
gastric mucosa
§ Gastric acid and pepsin release the vitamin from protein
binding in food and make it available to bind to cobalophilin, a
binding protein secreted in the saliva.
§ In the duodenum, cobalophilin is hydrolyzed, releasing the
vitamin for binding to intrinsic factor
§ Pancreatic insufficiency can therefore be a factor in the
development of vitamin B12 deficiency
 Vitamin B12
(Function)
§ Methylmalonyl CoA mutase, leucine aminomutase, and
methionine synthase are vitamin B12-dependent enzymes
§ Methylmalonyl CoA is formed as
üan intermediate in the catabolism of valine
üand by the carboxylation of propionyl CoA arising in the
catabolism of isoleucine, cholesterol, and, rarely, fatty acids
with an odd number of carbon atoms
üor directly from propionate, a major product of microbial
fermentation
§ It undergoes vitamin B12-dependent rearrangement to
succinyl-CoA, catalyzed by methylmalonyl-CoA isomerase
Vitamin B12
(Function)
 Vitamin B12
(Deficiency)
§ Pernicious anemia arises when vitamin B12 deficiency
blocks the metabolism of folic acid, leading to functional
folate deficiency
§ This impairs erythropoiesis, causing immature precursors of
erythrocytes to be released into the circulation
(megaloblastic anemia)
§ The commonest cause of pernicious anemia is failure of the
absorption of vitamin B12 rather than dietary deficiency
§ This can be due to failure of intrinsic factor secretion caused
by autoimmune disease of parietal cells, to generation of anti-
intrinsic factor antibodies, or gastrostomy
Break
 Folic Acids
(Concepts)
§ The active form of folic acid is tetrahydrofolate (THF)
 Folic Acids
(Function)
§ Tetrahydrofolatecan carry one-carbon fragments attached to
(Methyl, Methylene, Methenyl, Formyl, and Formimino THF)
§ 5-Formyl-THF is more stable than folate and is therefore
used pharmaceutically in the agent known as folinic acid
 Folic Acids
(Inhibitors)
§ The methylation of (dUMP) to (dTMP), catalyzed by
thymidylate synthase, is essential for the synthesis of DNA.
§ methylene-THF is reduced to a methyl group with release of
DHF
§ DHF is then reduced back to THF by dihydrofolate
reductase
§ Methotrexate (anticancer), trimethoprim (antibacterial), and
pyrimethamine (antimalarial) are DHF reductase inhibitors
 Folic Acids
(Deficiency)
§ since the major source of THF for tissues is methyl-THF, the
role of methionine synthase is vital and provides a link
between the functions of folate and vitamin B12
§ Impairment of methionine synthase in B12 deficiency results in
the accumulation of methyl-THF—the “folate trap.”
§ There is therefore functional deficiency of folate secondary to
the deficiency of vitamin B12
§ Folate deficiency causes Megaloblastic Anemia
.
 Folic Acids
(Deficiency)
§ Supplements of 400 μg/d of folate begun before conception
result in a significant reduction in the incidence of neural tube
defects as found in spina bifida.
§ Elevated blood homocysteine is an associated risk factor for
atherosclerosis, thrombosis, and hypertension
§ Folate supplements will treat the megaloblastic anemia of
vitamin B12 deficiency but may enhance the development of
the (irreversible) nerve damage found in B12 deficiency
§ There is also antagonism between folic acid and the
anticonvulsants used in the treatment of epilepsy
 Biotin
(Concepts)
§ Biotin is widely distributed in many foods as biocytin (ε-
amino-biotinyl lysine), which is released on proteolysis
§ It is synthesized by intestinal flora in excess of requirements
 Biotin
(Function)
§ Biotin functions to transfer carbon dioxide in a small number of
carboxylation reactions
§ Required as coenzyme acetyl-CoA carboxylase, pyruvate
carboxylase, propionyl-CoA carboxylase, or methylcrotonyl-
CoA carboxylase
§ Biotin also has a role in regulation of the cell cycle, acting to
biotinylate key nuclear proteins.
 Pantothenic Acid
(Function)
§ Pantothenic acid has a central role in acyl group metabolism
when acting as the pantetheine functional moiety of
coenzyme A (CoA) or acyl carrier protein (ACP)
§ The pantetheine moiety is formed after combination of
pantothenate with cysteine, which provides the -SH
prosthetic group of CoA and ACP
§ CoA takes part in reactions of the citric acid cycle, fatty acid
synthesis and oxidation, acetylations, and cholesterol
synthesis
§ ACP participates in fatty acid synthesis
§ The vitamin is widely distributed in all foodstuffs, and
deficiency has not been unequivocally reported in human
beings
 Ascorbic Acid
(Concepts)
§ Vitamin C is a vitamin for human beings and other primates,
the guinea pig, bats, passerine birds, and most fishes and
invertebrates
§ other animals synthesize it as an intermediate in the uronic
acid pathway of glucose metabolism
§ In those species for which it is a vitamin, there is a block in
that pathway due to absence of gulonolactone oxidase
 Ascorbic Acid
(Function)
§ Vitamin C is the coenzyme for two groups of Hydroxylases:
ü copper-containing hydroxylases and
ü the α-ketoglutarate-linked iron-containing hydroxylases
§ it has a number of nonenzymic effects due to its action as a
reducing agent and oxygen radical quencher
§ Dopamine -hydroxylase is a copper-containing enzyme
involved in the synthesis of the catecholamines
norepinephrine and epinephrine from tyrosine in the adrenal
medulla and central nervous system
§ During hydroxylation, the Cu+ is oxidized to Cu2+; reduction
back to Cu+ specifically requires ascorbate
 Ascorbic Acid
(Function)
§ A number of peptide hormones have a carboxyl terminal
amide which is derived from a glycine terminal residue.
§ This glycine is hydroxylated on the α-carbon by a copper-
containing enzyme, peptidylglycine hydroxylase, which,
again, requires ascorbate for reduction of Cu2+
 Ascorbic Acid
(Function)
§ Many of iron-containing enzymes are involved in the
modification of precursor proteins:
ü Proline and lysine hydroxylases are required for the
postsynthetic modification of procollagen to collagen,
ü and proline hydroxylase is also required in formation of
osteocalcin and the C1q component of complement.
ü Aspartate β-hydroxylase is required for the postsynthetic
modification of the precursor of protein C, the vitamin K-
dependent protease which hydrolyzes activated factor V in the
blood clotting cascade.
ü Trimethyllysine and γ-butyrobetaine hydroxylases are
required for the synthesis of carnitine.
 Ascorbic Acid
(Deficiency)
§ Signs of vitamin C deficiency in scurvy include skin changes,
fragility of blood capillaries, gum decay, tooth loss, and bone
fracture, many of which can be attributed to deficient collagen
synthesis
§ vitamin C enhances the absorption of iron, and this depends
on the presence of the vitamin in the gut
Thanks