15 Vitamins and Minerals

Fat Soluble Vitamins

Water Soluble Vitamins
Minerals

VITAMINS Retinoic acid: Normal morphogenesis, growth and

Retinol:
Vitamins are organic compounds occurring in small
Vitamin A, in the strictest sense, refers to Retinol

Fat soluble vitamins: Vitamins A, D, E and K Mor e than 60 0 carote noids in na ture, and
Water soluble vitamins: B Complex Vitamins and
vitamin A

Vitamins are generally not synthesized by the humans,

They are: Lutein and Zeaxanthin: Protect against macular

degeneration
Vitamin K, Biotin, and pantothenic acid by the LycopeneQ:

Vitamin A Metabolism

Vitamin A

Reductase
Cleaved in the intestine by a
the intestinal lumen to Retinol and absorbed into the
intestinal cells
All compounds chemically related to retinol are called
to retinol esters and transported in ChylomicronsQ
Retinal: 11 cis retinal to Liver
352 Self Assessment and Review of Biochemistry

Functions of Vitamin A

containing pigments
Rhodopsin
- Most light sensitive pigment present in rods
- Formed by covalent association between 11
cis retinal and 7-transmembrane rod protein

Biologically important retinoic acids are all Trans-

retinoic acid and 9 -cis retinoic acid
They act like steroid hormones
They bind to

Retinoic Acid Receptors (RARs) binds with high

acid
Retinoic X receptor (RXRs) binds only to 9 cis retinoic
acid

mucosa

Eyes
Metabolism of Vitamin A

St
Stored in the as called as Xerophthalmia

blindness or Nyctalopia is the earliest symptom

Carried to target sites in the plasma as trimolecular
complex bound to Retinol Binding Protein (RBP) and
Transthyretin. epithelium appearing on the sclera)
 Vitamins and Minerals 353

Blinding corneal ulceration and necrosis

Men
Women
produce Q
or Papular
or Lactation
Toad Skin
Squamous Metaplasia in the mucus secreting

tract retinol equivalent

Vitamin A from liver stores.

introduced the term Retinol Activity Equivalent

All transretinoic acid in acute Promyelocytic

Animal sources
Fish liver oilsQ

Organelle damaged in hypervitaminosis is

Acute toxicity: Pseudotumor cerebriQ (headache,

dizziness, vomiting, stupor, and blurred vision, Plant sources
Richest plant source is
Others are GLV like Spinach, Amaranth, Green and
and hyperlipidemia

months
Weight loss, anorexia, nausea, vomiting, bony
exostosis, bone and joint pain, decreased cognition,
hepatomegaly progresses to cirrhosis
Retinoic acid stimulates osteoclast production and
activity leading to increased bone resorption and once in 6 months
high risk of fractures, especially hip fractures

Dark adaptation time

Carotenoids Serum Vitamin A by
354 Self Assessment and Review of Biochemistry

Vitamin D

Ergocalciferol (Vit D2): Commercial Vitamin D

Vitamin D status
Cholecalciferol (Vit D3):

in the Q

Q
through
-
upregulate
its in the skin by photo-
- D inhibit the enzyme
When Ca + level is high, kidney produces the rela-
-
in the

- Functions of Vitamin D
ments in the gut
Action on intestine
plasma Vitamin D increases Ca absorption
and (a member

.
Action on kidney
Vitamin D increases Ca and Phosphorus reabsorption

Action on bones

binds to its receptor (RANK) located in

cells into mature osteoclasts

They dissolve bone and release calcium and phos-

located in the mitochondria

Metabolism of Vitamin D
C - macrophages causes a transcription-induced increase
 Vitamins and Minerals 355

D then stimulates the synthesis , an

in incidence of -
Colon cancer
Breast cancer Inspite of secondary hyperparathyroidism,
Prostate cancer

Mineralization of bones

bones An autosomal recessive disorder

It stimulates osteoblast to synthesize calcium binding Due to mutations in the gene encoding the vitamin
D receptor causing end-organ resistance to the active

X-linked dominant disorder

The most common hypophosphatemic rickets
PHEX ( osphate-
regulating gene with homology to Endopeptidases
on the X chromosome)

an indirect role in inactivating a phosphatonin or

Hypophosphatemia with normal PTH, normal

increases

An autosomal recessive disorder An autosomal dominant condition

356 Self Assessment and Review of Biochemistry

patients have

Hypophosphatemia with normal PTH, normal

Requirement of Vitamin D

Extremely rare disorder due to mutation in the gene
encoding dentin matrix protein 1, which results in
Vitamin D is toxic in excess
day
Some infants are sensitive to intakes of vitamin D as
low as 50 µg/day , resulting in an elevated plasma
Q

Autosomal recessive disorder due to mutation in the

bloodpressure, and
proximal renal tubules

Although excess dietary vitamin D is toxic, excessive

exposure to sunlight does not lead to vitamin D

pain short stature with disproportionate decrease in the precursor, 7-dehydrocholesterol, and prolonged

PTH ALP
N/Decrease Decrease Increase Decrease Increase
Increase
N/Decrease Decrease Increase N Decrease Increase
N/Decrease Decrease Increase N Increased Increase
N/Decrease Increase Increase N Decrease Increase
N Decrease Normal N Increase
Decrease
N Decrease Normal N Increase
Decreased
 Vitamins and Minerals 357

Bronchopulmonary dysplasia
Sunlight

Required daily allowance

Vitamin E
Vitamin E is a collective name for all stereoisomers of
tocopherols and tocotrienols
Q

Vitamin K
Naphthoquinone derivative with long isoprenoid
Chromane (Tocol) ring with isoprenoid side chain side chain
Letter K is the abbreviation of German word,
oagulation Vitamin.

Q
Synthesized by Bacterial
pyroxyl radical scavenger that protects low-density Flora
Vitamin K3: (and Menadiol diacetate):
Synthetic,

Q
Vitamin K is required for the post-translational carboxy-
lation of glutamic acid (Gamma Carboxylation), which is

axons and result in posterior column and spinocere- Factors VII, IX, and X
bellar symptoms Protein C, protein S
The erythrocyte membranes are
- Matrix Gla protein
tion, leading to hemolytic anemia
Nephrocalcin in kidney
initially characterised by

position and vibration sense

carboxylation by com-
Skeletal myopathy petitively inhibiting the enzyme that convert vitamin K
Pigmented retinopathy

Elevated prothrombin time, bleeding time

358 Self Assessment and Review of Biochemistry

Typically a symmetric motor and sensory neuropathy

Hemolysis
Hyperbilirubinemia
Horizontal Nystagmus
Ophthalmoplegia
Truncal ataxia
B Complex Vitamins
Vitamin C
Thiamin (Vitamin B1)
Amnesia

Acute pernicious (fulminating) beriberi (shoshin beriberi),

in which heart failure and metabolic abnormalities
predominate.
Thiamine Pyrophosphate (TPP) also called Thiamine
Erythrocyte Transketolase activity is reduced

Thiamine generally function in the decarboxylation reac-

tion of alpha keto acids and branched chain amino acids
Q
which convert Pyruvate
to Acetyl CoA Q
Q
in Citric Acid respiration

CoA
Q
which proteins
Chain Amino acids Act as respiratory coenzyme and an electron donor
Q
in Q

They are FAD (Flavin Adenine Dinucleotide) and FMN (Flavin

Mononucleotide)

BeriBeriQ
Two types
: Marked peripheral vasodilatation,
-
noea, tachycardia, cardiomegaly, pulmonary and

: Involves both peripheral and central

Contd...
 Vitamins and Minerals 359

Contd... Contd...
Q

Magenta tongue (Glossitis), angular stomatitis,

Other function of NAD
, Cheilosis, , anemia
NAD is the source of ADP-ribose for the ADP-ribosylation of
Biochemical Assessment of Nutritional status of
proteins and polyADP-ribosylation of nucleoproteins involved
in the DNA repair mechanism
Reductase by FAD added in vitro
Pellagra
Photosensitive Dermatitis: Symmetric dermatitis in
the sun exposed areas
Skin lesions are dark, dry and scaling
Casal’s NecklaceQ
neck
Dementia
Niacin or Nicotinic Acid (Vitamin B3) Insomnia, irritability, and apathy and progresses
Not strictly a Vitamin
depressive psychosis
Diarhea can be severe resulting in malabsorption due

Advanced Pellagra can result in death

Adenine Dinucleotide) and NADP+(Nicotinamide

Dementia

Mainly for Reductive Biosynthesis of steroids and CholesterolQ,

Free radical ScavengingQ, Formation of deoxyribonucleotides, limiting enzyme in Niacin synthesis.
One carbon metabolism.

20 mg/day
Folatereductase

Contd... Gastric irritation

360 Self Assessment and Review of Biochemistry

Hepatic toxicity is the most serious toxic reaction Tryptophan metabolism

with sustained release niacin presents with jaundice, C involved in the synthesis
-
nant hepatitis is excreted
Other toxic reactions include glucose intolerance,

Heme synthesis

1 antagonist
Glycogenolysis

Niacin reduces plasma triglyceride and LDL-C levels

Catecholamines
Peripheral neuropathy
Personality changes that include depression and
Pyridoxine
Pyridoxal
: Due to decreased
Pyridoxamine
heme synthesis

muscleQ
Oxaluria:

Pyridoxal Phosphate (PLP) Homocystinuria:

Q
Synthase
Q Xanthurenic Aciduria:
Transamination Cardiovascular risks:
Drugs that interact with carbonyl group and causes PLP

Decarboxylation of amino acids

Classic homocystinuria (due to cystathionine beta
Glutamate: GABA
5-Hydroxy Tryptophan: Serotonin
Histidine: Histamine
Cysteine: Taurine
Serine: Ethanolamine
Carpal Tunnel syndrome
Premenstrual syndrome
Transulfuration
Schizophrenia

amino acids

Enzymes are Cystathionine Beta Synthase and

Contd...
 Vitamins and Minerals 361

Contd... Pantothenate kinase associated neurodegeneration

Rare autosomal recessive neurodegenerative disorder

and vitamin D

prognosis.
area within the hypointense area)
Sometimes acanthocytosis
Neuropathologic examination indicates excessive
Erythrocyte Transaminase activity
globuspallidus and substantianigra
Similar disorders are grouped as neurodegeneration

Excess Pyridoxine may lead to Sensory Neuropathy.

regulation by histone biotinylation.

everywhere

intestine
Vitamin that contains Beta Alanine
Vitamin present in Coenzyme A (CoA) and Acyl
Carrier Protein (ACP) in Fatty Acid Synthase

Acetyl CoA
Succinyl CoA
HMG CoA
Avidin
Protein present in the raw egg white

in raw egg inhibit biotin

Acetylation
Citric acid cycle

This property is used in

ELISA test
362 Self Assessment and Review of Biochemistry

Source of Formimino THF

Mental changes (Depression, hallucination)
paresthesia, anorexia, and nausea
A scaling, seborrheic and erythematous rash around
Serine to Glycine
Homocysteine to Methionine

Folic Acid or Vitamin B9

Methyl (CH3)
Methylene (CH ) 5-Formyl-tetrahydrofolate is more stable than folate and is
Methenyl (CH) therefore used pharmaceutically (known as folinic acid), and
Formyl (CHO)

N are Formyl, Formimino or methyl

N are Formyl
Both N and N Red Cell Folate
Histidine Load testQ or FIGLU excretion test
AICAR [Amino Imidazole Carboxamide Ribose 5
Methylene THFQ
Serum Homocysteine
SerineQ
Peripheral Blood Smear (Macrocytes, tear drop cells,
units
hypersegmented neutrophils, anisopoikilocytos
SerineQ Q
is the enzyme

Source of Methylene THF

Serine to Glycine by Serine Hydroxy Methyl

Glycine
 Vitamins and Minerals 363

Cobalamin binding proteins

because THF derivatives Cobalamin binding proteins in the saliva are called
are involved in purine synthesis and thymidylate Haptocorrins or Cobalophilin or R Binders
Synthesis

lead to this condition

stomach and binds to salivary proteins called

during Q
by binding
pregnancy
to IF receptor
Atrophic glossitis
IF receptor in the ileum is called

Major Cobalamin transport protein in plasma is

Transcobalamin II (TC II)Q

Prophylactic Folic Acid during pregnancy reduce

At the target tissues by receptor mediated endocytosis

into cancers
Nutritional

This
So Folic Acid should be avoided in established
means that strict vegetarians (vegans) are at risk of

Malabsorption-pernicious anemia
-
Contain
ticanemia caused by autoimmune gastritis and an

Gastric causes

abnormality

Leucine Amino Mutase Intestinal causes

Intestinal stagnant loop syndrome: jejunal

Absorption of cobalamin

Active mechanism: Site is IleumQ

Selective malabsorption with proteinuria
-
Imerslund Syndrome
364 Self Assessment and Review of Biochemistry

Imerslund-Gräsbeck Syndrome
Congenital Cobalamin Malabsorption Serum Cobalamin
Autosomal Recessive Megaloblastic Anemia Serum Methyl Malonate (This helps to distinguish
Tropical sprue between Megaloblasticanemia due to Cobalamin

Serum Homocysteine
Fish tapeworm
Schilling Test using Radioactive labelled Cobalt-60
Diphyllobothriumlatum) lives
Urine Homocystine and MMA

Vitamin C (Ascorbic Acid)

When acting as a methyl donor, S-adenosyl methionine

uronic Acid PathwayQ
Humans and higher Primates cannot due to absence
Q

radicals (Antioxidant)

lysine and Proline

Phenyl Pyruvate to Homogentisic Acid

Bile Acid Synthesis in 7 alpha Hydroxylase
Iron Absorption: Favor Iron absorption by conversion

Folate trap

Scurvy
Megaloblasticanemia

Homocysteine to Methionine

Malonyl CoA Mutase which leads to decreased

purpura
CoA Splinter hemorrhage, bleeding gums, hemarthroses,
subperiosteal hemorrhage
Anemia
Late stage are characterized by edema, oliguria,
 Vitamins and Minerals 365

Barlows Syndrome (Infantile Scurvy)

s
Niacin

Niacin
Cobalamin
Folate
Biotin
Pernicious anemia = megaloblasticanemia

Q
Vitamin E
Vitamin C d
Beta Carotene

Vitamin C
Vitamin C
Beta Carotene
Vitamin E Vitamin A

Niacin
Vitamin D

Vitamin E

Biotin MIN
Vitamin D

Macrominerals (Major elements)

Calcium, Magnesium, Phosphorus, Sodium,

Micromineral (Trace element)

Iron, Iodine, Copper, Cobalt, Mangenese,

Molybdenum, Selenium, Zinc, and Fluorine
Ultra trace elements
Folic Acid
Biotin
IRON
Contain Pantoic Acid
and
366 Self Assessment and Review of Biochemistry

is Hemosiderin
500
Transferrin
Iron Stores

( )
Q

Iron is transported in plasma in the Fe

transport protein,

Catalase
Synthesized in the

with two iron

Aconitase
binding sites
Transferrin
Ferritin
monoferric diferric

bound iron is very rapid—typically

Normal saturated with Iron

transferrin receptors

Ferritin

, by contrast, is

type

and stability to intracellular iron levels

Seen in Intestinal cells, Liver, Spleen and Bone marrow
declines

Contd...
 Vitamins and Minerals 367

Contd...

as well as in
Alcoholism

, which can be measured by isoelectric

Metabolism of iron

Site

Heme iron is absorbed by a

Iron is absorbed in the Q

)
) by a brush

Vitamin C

proton- coupled

,Zn ,Pb ,Cu ) Absorption of Iron

368 Self Assessment and Review of Biochemistry

Once inside the enterocytes, iron can either be stored

as protein
membrane into the circulation by the iron exporter
protein, or site where it binds to HFE protein
or
This protein may interact with the copper-containing
protein a protein similar to ceruloplasmin

cascade (ERK-MAPK cascade)

Thus, Fe is converted back to Fe

Homeostasis

proteins called SMADs, which subsequently results

Hepcidin binds to the cellular iron exporter, in

degradation
Two molecules secreted by erythroblasts, growth

gastrulation 1 (TWSG1)
depressed iron recycling by macrophages
They
Together, these result in a reduction in circulating

When plasma iron levels are high, hepatic synthesis by cytokines such

level

Transcription) Pathway

Bone Morphogenic Proteins (BMPs) and Hemojuvelin

Erythropoietic signals

Hypoxia
Hypoxia is

Liver cells monitor iron levels using an iron sensing synthesis is controlled by hypoxia-inducible
 Vitamins and Minerals 369

Contd...
Ext ra corpuscula r hemo globin is bound by
Patients suffering from

into three stages

, in which the

The second stage is

Contd... impaired
370 Self Assessment and Review of Biochemistry

The third stage is , where

TIBC
RBC Protoporphyrin

-
-

Iron stores -
- - -

iron Normal/ Variable

0 0 Smear Micro/
stores mic
targeting
Serum
< 50 Normal to Normal

> 400
NL < 50
Transferrin
Saturation NL satura

NL
sideroblasts
Normal Normal Normal

Protopor NL pattern -

NL NL NL

0 0
stores
Serum ferritin Decreased Decreased Decreased

Total iron bind Increased > Increased

increased > 400

Normal Decreased Decreased

< 50
Transferrin Normal Decreased Decreased

Normal Increased Increased

Soluble trans Increased Increased Increased

ferrin receptor

Normal Normal Normal

mic
 Vitamins and Minerals 371

Diagnosis of Wilson’s Disease

condition

Gold Standard investigationQ is Liver BiopsyQ with

Diabetes Mellitus

Serum Ceru
Carcinoma loplasmin mg/L

Absent Present in > 99% if

ring

patients
c Urine Copper
atic patients

Liver Copper

Autosomal recessive
Treatment

transporting ATPase in the cells Zinc Trientene

- pensation
min
Copper accumulate in cells leading to copper deposits Mild Trientene and Zinc Penicillamine and
Zinc
Moderate Trientene and Zinc
tation
Severe Trientene and Zinc
tion
Initial neurologic/ Zinc
and Zinc
Maintenance / Pre Zinc Trientene
obstructive liver disease
nant/ Pediatric
372 Self Assessment and Review of Biochemistry

The di

Serum Bilirubin

Mutation in ATP7A gene

X linked recessive condition
Selenocysteine
Selenium is being actively studied as a chemo-
preventive agent against certain cancers, such as

ZINC

in the body

proteins, DNA, and RNA and plays a structural role CHROMIUM

in ribosomes and membranes

with impaired glucose tolerance, by increasing

DNA

CNS damage.
in children, decreased taste sensation (hypogeusia),

Rare autosomal recessive disorder characterized by

abnormalities in zinc absorption
in tooth enamel as well as brittle bone (skeletal

muscle wasting, depression, irritability, and a rash

The rash is characterized by vesicular and pustular Zinc containing protein present in the Saliva: GustenQ
crusting with scaling and erythema Mineral stabilize hormone insulinQ Zinc
 Vitamins and Minerals 373

Q Contd...

RDA
tolerance: ChromiumQ ZincQ
SeleniumQ
and Prostatic Secretion
-
genesis: Zinc
Garlicky odor in breath is seen in: Selenosis (Due to
Dimethyl selenide)
Cobalt Constituent of Vitamin
Selenium toxicity lead to Kaschinbeck Disease
Low Selenium level leads to Keshan disease (Endemic
Cardiomyopathy)
Calcium dependent Cysteine Protease are called Fluoride Constituent of Bone and Dental caries
Calpain
Calpain associated with Type II Diabetes Mellitus: Iodine
Calpain 10
Severe neurologic

Total Calcium level in the bodyQ

Recommended Daily Allowances (RDA) of important
Selenium
Minerals
RDA
muscle degeneration
CalciumQ
Vitamin E
Zinc Cofactor for
IronQ

IodineQ -
congenital
malformation Impaired
500 mg
Magnesium 400 mg Mangenese
Mangenese
Sodium
Potassium
Copper
merase
Contd...

Glutathione (Ref: Harper 30/e p546) retardation, precocious puberty and obesity