Vitamins and Minerals

Gita Vita Soraya, MD PhD

Vitamins – Learning Objectives

1 Definition and classification of vitamins

2 Characteristic differences between water- and lipid-soluble vitamins

3 Daily requirements and sources of the vitamins

4 Structure, function, and metabolism of the vitamins

5 Consequences and manifestations of hypervitaminosis and hypovitaminosis

Definition and Classification of Vitamins

Vitamin Definition

Vitamins are organic nutrients which serve

numerous biochemical and physiological Vitamin
functions. Generally, the organism is
incapable of producing most vitamins on its
own
Water-Soluble Lipid-Soluble
Vitamins Vitamins

Vitamin Classification Vitamin B-complex Vitamin A

Vitamin C Vitamin D
Based on its solubility, vitamins are Vitamin E
Vitamin K
classified as water-soluble or lipid-soluble
 10.3 Li

Characteristics of Water & Lipid Soluble Vitamins studies identified two general classes of such com- leads to d
pounds: those soluble in nonpolar organic solvents (fat- ets, for w
soluble vitamins) and those that could be extracted from dramatic
Water-Soluble Vitamins foods with Lipid-Soluble Vitaminsvitamins).
aqueous solvents (water-soluble mercial p
Eventually the fat-soluble group was resolved into the terol of y
four vitamin groups A, D, E, and K, all of which are iso- with sligh
prenoid
Apolar compounds synthesized
hydrophobic by the condensation
compounds made up of of sterol D r
Hydrophilic compounds
multiple isoprene units. Two of these (D and A) serve D2 is com
isoprene units.
as hormone precursors. suppleme
Passive or facilitated absorption in the intestines tamin D m
CH3
ulates ge
Relatively fast metabolism and excretion. Cannot CH2 C CH CH2 synthesis
Isoprene
be stored in the body (except for Vitamin B12)– Vitam
must be supplied continuously through diet. Any Vitamin D3, also called cholecalciferol, is nor- as a horm
mally formedfat
Requires in the
for skin from 7-dehydrocholesterol
absorption in
(slower), and fat brate eye
excess is excreted in the urine
a photochemical reaction driven by the UV component in the cell
malabsorption leads to deficiencies
of sunlight (Fig. 10–20). Vitamin D3 is not itself biolog- regulates
ically active, but it is converted by enzymes in the liver ithelial tis
Mainly function as coenzymes and cofactors in an and kidney toCan be stored in the bodya hormone
1,25-dihydroxycholecalciferol, ingredien
enzymatic reaction, also as molecular transporters that regulates calcium uptake in the intestine and cal- treatment
Serves
cium multiple
levels in kidneyfunctions, vitaminsofAvitamin
and bone. Deficiency and D Din min A der
particular serve as hormones. They do not act as
coenzymes
CH3 (with the exception of Vitamin K)
CH3 oxidat
of alde
CH3 to acid

CH3
CH3
2 CH3
6 CH3
CH3
CH3 CH3 7
 Fluorine Tea, fish consumed whole
Probably not essential but has 4 mg (210 μmol)
positive effects on dental
health
Iodine Seafood, dairy products Essential component of thyroid 150 μg (1.2 μmol)
hormones
Iron Animal products, especially Component of all heme Men: 8 mg (142 μmol)
red meat pigments and enzyme activator Women: 18 mg (320 μmol)
Manganese Grains, nuts, leafy vegetables
CHAPTEREnzyme cofactor Laboratory and
56 Nutrition: 2.3 mg (42 μmol)
Clinical Aspects 1159.e3
Molybdenum Animal products, grains, Enzyme cofactor 45 μg (47 nmol)
Vitamin Daily
legumes Requirement and Sources
TABLE 56.1 AAnimal
Selenium Summaryproducts,of Nutrients,
grains, fish Their cofactor
Enzyme Sources, Function(s), and
60 μg (76 Recommended
nmol)
Daily Intakes for Adult
Zinc Males—cont'd
Animal products, poultry, eggs Enzyme cofactor 10 mg (150 μmol)

Nutrient Source VITAMINS

Principal Function(s) Daily Requirement
A Oily fish, eggs, dairy products MACRONUTRIENTS
Vision, 900 μg
epithelial differentiation
VITAMINS
B112(thiamin)
(cobalamin) Wheat
Animal germ, eggs, yeast
and bacterial sources Enzyme
Cofactorcofactor
in 1-C transfers; >1.4
1 μgmg
B2 (riboflavin) Milk,
onlydairy products, green Component of flavoproteins
essential for Men: 1.3 mg
purine and hence
vegetables, yeast, offal nucleic acid synthesis Women: 1.1 mg
C3(ascorbic
B (nicotinic acid)
acid) Vegetables,
Widely fruit (especially
distributed Antioxidant;ofelectron
Component NAD+ anddonor Men:16mg
NADP+
Men: 90 mg
citrus) CHAPTER 56 Nutrition:
in various Laboratory and
enzyme-catalyzed Clinical
Women:
Women: 14
Aspects
75mg
mg 1159.e3
reactions
B5 (pantothenic acid) Widely distributed Component of coenzyme A 5 mg
D (calciferol) Oily fish; dietary provision Stimulates absorption of dietary 600 IU (15 mg)
B6 (pyridoxine and Widely distributed Enzyme cofactor 1.3 mg
derivatives)56.1 A Summary
TABLE of Nutrients, Their Sources, Function(s), and Recommended
usually insufficient for calcium and phosphate;
normal requirements essential for bone health.
Daily
B Intakes
E 7 (biotin)
for Adult
Widely Males—cont'd
distributed
Vegetable oils, cereals Enzyme cofactor in 1-C transfers No
Antioxidant 15recommendation
mg as α-tocopherol
B
K 9 (folic acid) Leafy vegetables, yeast,
Green leafy vegetables eggs Cofactor in 1-C transfers;
Synthesis of Gla proteins 120μg
400 μg
Nutrient Source Principal
essential Function(s)
(including for purine andfactors)
coagulation hence Daily Requirement
MACRONUTRIENTS
VITAMINS
nucleic acid synthesis
*Actual requirements may be modified considerably by physiological and pathological factors. NB molar units are not in general use
forB12 (cobalamin)
vitamins Animal
in the context of and bacterial
recommended daily sources Cofactor
allowances but in 1-C for
are included transfers; 1 μg
minerals to aid comparison with reference plasma
concentrations. only essential for purine and hence
nucleic acid synthesis
C (ascorbic acid) Vegetables, fruit (especially Antioxidant; electron donor Men: 90 mg
on an adequate supply of oxygen is absolute. With the addi- basis of the complex interaction of neural and hormonal
citrus) in various enzyme-catalyzed Women: 75 mgon July 11, 2019.
tional exception of water,
Downloaded deficiency
for Gita Soraya in any of the nutrients
(gsoraya@student.unimelb.edu.au) mechanisms
at The University that
of Melbourne from controls appetite
ClinicalKey.com.au and in health adjusts food
by Elsevier
discussed in this chapter only becomes life threatening after a reactions
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
intake to the body’s requirements. This topic is considered in
D (calciferol)
period Oily fish;Deprivation
of weeks or even months. dietary provisionof oxygen leadsStimulates detail
absorption
later of
indietary
this chapter,600 butIU (15 mg)
it is salutary to consider that
to brain death within a fewusually insufficient for
minutes. calcium and an phosphate;
average healthy man may consume food providing some
normal requirements essential 9for× bone (56.6 × 105 MJ) of energy per year, equivalent toAdapted from: Burtis CA, Bruns DE.
health.
105 kcals
POINTS TO REMEMBER
E Vegetable oils, cereals Antioxidantapproximately 130 kg of15 mg as α-tocopherol
nonaqueous body mass, yet maintain2014. Tietz Fundamentals of Clinical
K Green leafy vegetables Synthesis of theGlasame body weight year
proteins 120 μg after year. In the short term, theChemistry and Molecular Diagnostics.
Nutrients
(includingprovision
coagulation offactors)
sufficient energy substrates for normal functionElsevier Health Sciences.
• Nutrients are conventionally classified as being macronu- is primarily dependent on blood glucose homeostasis, a topic
trients
*Actual (carbohydrate,
requirements may be fat, protein,considerably
modified and the major minerals) and pathological
by physiological that is considered inmolar
factors. NB detailunits
in Chapter
are not in57.
general use
and micronutrients
for vitamins in the context(vitamins and tracedaily
of recommended elements).
allowances but are included for minerals to aid comparison with reference plasma
• The majority of vitamins and trace elements act as cofac-
concentrations. Deficiency
tors for enzyme-catalyzed reactions or as prosthetic groups Because carbohydrates are not essential dietary components,
for enzymes. there is no specific carbohydrate deficiency syndrome.
on• an
Some vitamins
adequate and trace
supply elements
of oxygen have important
is absolute. antioxi-
With the addi- However,
basis of thebecause
complex carbohydrates
interaction of provide
neuralthe
andmajor source
hormonal
dant properties.
tional exception of water, deficiency in any of the nutrients mechanisms that controls appetite and in health adjusts foodis
of energy in most diets, a deficiency of dietary carbohydrate
• Both excessive and inadequate intake of nutrients may virtually always a major contributor to generalized starvation.
Structure, Function & Metabolism of Lipid-Soluble Vitamins

Vitamin A (Retinol)
Vitamin A is a generic term for retinol, retinal ,
and retinoic acid . Retinal and retinoic acid are
active forms of vitamin A

The provitamin (precursor) of vitamin A is a

plant pigment β-carotene (and other
carotenoids)

Retinol is produced by cleaving beta carotenes

Oxidation of retinol produces retinal
Oxidation of retinal produces retinoic acid

Retinol derivatives have two main functions:

1. Hormonal function by retinoic acid, which is
a hormone that regulates gene expression
2. As pigment for the eye by retinal

Baynes JW & Dominiczak MH. 2018. Medical Biochemistry. Elsevier Health Sciences.
Structure, Function & Metabolism of Lipid-Soluble Vitamins
Vitamin D3 (cholecalciferol) is synthesized
in skin by UV radiation: Cholecalciferol is
Vitamin D3 (Cholecalciferol) formed from 7-dehydrocholesterol through
photochemical reaction in the skin

In the liver, cholecalciferol is hydroxylated to

form calcidiol (storage form of vitamin D).

In the kidney, calciol is hydroxylated into

1,25-dihydroxycholecalciferol (calcitriol)
hormone, which is the most active and
potent form of Vitamin D

Function of 1,25-dihydroxycholecalciferol:
1. Regulates calcium uptake in gut
2. Regulates calcium levels in kidney and bone
3. Regulates gene expression

Baynes JW & Dominiczak MH. 2018. Medical Biochemistry. Elsevier Health Sciences.
 Structure, Function & Metabolism of Lipid-Soluble Vitamins
2/04 1:06 PM Page 362 mac76 mac76:385_reb:

Vitamin E (Tocopherols) Dietary vitamin E is a mixture of several

compounds, known as tocopherols. Ninety
percent of vitamin E present in human tissues
10 Lipids
Structure of vitamin E family is in the form of α-tocopherol
(tocopherols).R 1 –R 3 can be methylated
d and cone cells of the retina to light, in a variety of combinations. R 4 is a
euronal signal to the brain. This role of
Vitamins E and K and the Lipid Quinones Are
polyisoprenoid chain. It is absorbed from the diet in the small
Oxidation-Reduction Cofactors
ibed in detail in Chapter 12. intestine with lipids.
was first isolated from fish liver oils; liver, Vitamin E is the collective
Baynes name for MH.
JW & Dominiczak a group of
lk, and butter are good dietary sources. closely related 2018.
lipidsMedical Biochemistry. all of
called tocopherols,
!-carotene, the pigment that gives car- which contain a substitutedElsevier Healthring
aromatic Sciences.
and a long iso- It is the most abundant natural antioxidant
atoes, and other yellow vegetables their prenoid side chain (Fig. 10–22a). Because they are hy-
olor, can be enzymatically converted to drophobic, tocopherols associate with cell membranes,
ciency of vitamin A leads to a variety of lipid deposits, and lipoproteins in the blood. Tocopherols
humans, including dryness of the skin, are biological antioxidants. The aromatic ring reacts
ous membranes; retarded development
Aromatic
with and destroys the most reactive forms of oxygen Tocopherol function:
d night blindness,(chromanole)
an early symptom
ring com- radicals and other free radicals, protecting unsaturated
diagnosing vitamin A deficiency. ■
Long isoprenoid side chain
fatty acids from oxidation and preventing oxidative 1. Serve as antioxidants: protects lipid
from oxidation by reactive oxygen
CH3 species (ROS) - the aromatic ring
HO CH3 CH3 CH3 reacts with and destroys free radicals
ntioxidant CH2 CH2 CH2 CH CH2 CH2 CH2 CH CH2 CH2 CH2 CH CH3
2. Involved in immune function, cellular
CH3 O CH3
CH3 signalling, gene expression
Nelson DL, Lehninger AL & Cox MM. 2008. Lehninger Principles of Biochemistry. Macmillan.
O

CH3 CH3 CH3 CH3

od-clotting
quinone) CH2 CH C CH2 "CH2 CH2 CH CH2 ! 2 CH2 CH2 CH CH3

O O
uronal signal to the brain. This role of
Oxidation-Reduction Cofactors
ed in detail in Chapter 12.
as first isolated from fish liver oils; liver, Vitamin E is the collective name for a group of
k, and butter are good dietary sources. closely related lipids called tocopherols, all of
!-carotene, the pigment that gives car- which contain a substituted aromatic ring and a long iso-
toes, and other yellow vegetables their prenoid side chain (Fig. 10–22a). Because they are hy-
lor, can be enzymatically converted to drophobic, tocopherols associate with cell membranes,
iency of vitamin A leads to a variety of lipid deposits, and lipoproteins in the blood. Tocopherols
umans, including dryness of the skin, are biological antioxidants. The aromatic ring reacts
us membranes; retarded development with and destroys the most reactive forms of oxygen
Structure,
night blindness, Function
an early symptom com- & radicals
Metabolism of radicals,
and other free Lipid-Soluble Vitamins
protecting unsaturated Vitamin K is a group of compounds that vary in
iagnosing vitamin A deficiency. ■ fatty acids from oxidation and preventing oxidative
the number of isoprenoid units. Two main
vitamers:
CH3 Vitamin K (Phylloquinone) 1. Phylloquinone (vitamin K1):
HO CH3 CH3 CH3
ioxidant CH2 CH2 CH2 CH CH2 CH2 CH2 CH CH2 CH2 CH2 CH CH3
• Found mostly in plants
CH3 AromaticOring CH3
Long isoprenoid side chain
• In the body it is the circulating form
CH3 2. Menaquinones (vitamin K2):
• Intestinal microflora converts from
O
phylloquinone
CH3 CH3 CH3 CH3
d-clotting • Hepatic stores
uinone) CH2 CH C CH2 "CH2 CH2 CH CH2 ! 2 CH2 CH2 CH CH3
• Subtypes differ by isoprenoid units
O

Vitamin K is widely distributed in plants,

Nelson DL, Lehninger
O O AL & Cox MM. 2008. Lehninger Principles of Biochemistry. Macmillan.
Absorption of vitamin K depends on the ability
lood
nt Structures of theCH
different forms of vitamin K to absorb fat
OH
CH2 C CH3
O
Vitamin K functions in blood clotting:
O The aromatic ring undergoes oxidation and
CH3O CH3
chondrial CH3 CH3
Baynes JW & Dominiczak
MH. 2018.
CH3Medical
reduction during the formation of
nzyme Q)
) CH3O CH2 CH C CH2 "CH2 CH C CH2 ! n
Biochemistry. Elsevier
CH2 CH C CH3
prothrombin. Prothrombin is a protein crucial
Health Sciences.
O in blood clot formation

O
CH3
CH3 CH3 CH3
hloroplast
! 4 to 8) CH3 CH2 CH C CH2 "CH2 CH C CH2 ! n CH2 CH C CH3
O
Hyper- and Hypo-vitaminosis of Lipid-Soluble Vitamins

Vitamins 365

Fat-soluble vitamins are associated with A. Vitamin supply

body fat and are often stored in tissues,
with circulating concentrations kept Healthy
relatively constant. nutrition Vitamin require-
ment satisfied
Hypovitaminosis occur in:
Vitamin poisoning
• Inadequate diet
Poor nutrition Vitamin
• Fat malabsorption (low fat diet, Malnutrition A and D
Antibiotics
disease of liver or gallbladder, Disturbed Vitamin intake Hypervitaminosis
inflammatory bowel diseases such as resorption
e
rdos Excess
celiac or Crohn’s) Hypo- Ove vitamins
Diseases
vitaminosis Urine
Hypervitaminosis occurs frequently in
lipid-soluble vitamins (especially A and
B. Lipid-solubleKoolman
vitamins
J, Röhm KH, Wirth J, & Robertson M. 2005. Color Atlas of
D) because it can be stored in the body Biochemistry. Volume 2. Stuttgart: Thieme.
* Adult daily Provitamin Functional form Important for
* requirement

β-Carotene
Retinal Sight
A Vegetables
H3C CH3 CH3 CH3 Fruit Visual pigments
CH2OH

CH3 Retinol Retinol Sugar

transport
1 Coenzyme
Milk

Hyper- and Hypo-vitaminosis of Lipid-Soluble Vitamins
Toxicity signs: CNS (headache,
nausea), liver (hepatomegaly),
skin (dryness and alopecia)
Teratogenic in excess
Vitamin A
Night blindness (xerophthalmia)
Skin keratinization
Elevated calcium levels cause
blood vessel contraction, high
blood pressure, calcinosis
Vitamin D
Rickets (in children):
poor mineralization
Extremely rare, but deficiency cause
Osteomalacia (in adults):
demineralization
Hypervitaminosis occurs frequently in lipid-soluble
vitamins because it can be stored in the body
Vitamin K toxicity has not been
A high intake of vitamin E can
reported
antagonize vitamin K and
potentiate anticoagulant activity,
leading to a bleeding diathesis.
Vitamin E Vitamin K
Impaired blood clotting &
hemorrhage
severe neurological dysfunction. Small % of newborns suffer
from hemorrhagic disease of
the newborn
Structure, Function & Metabolism of Water-Soluble Vitamins

B-Complex Vitamins
Important Coenzymes in Which B Vitamins are Present B-complex vitamins are essential
B Vitamin Coenzymes Groups Transferred for normal metabolism and serve
Thiamin (B1) Thiamin pyrophosphate (TPP) Aldehyde as coenzymes in many reactions
Riboflavin (B2) Flavin mononucleotide (FMN) Hydrogen atom
in carbohydrate, fat, and protein
Flavin adenine dinucleotide (FAD) metabolism
Niacin (B3) Nicotinamide adenine dinucleotide (NAD+) Hydrogen atom
Nicotinamide adenine dinucleotide phosphate (NADP+) The greater the caloric intake, the
larger the requirement for B
Panthothenic Acid Coenzyme A (CoA) Acyl group vitamins. Increased energy
(B5)
supply, in particular from simple
Pyridoxine (B6) Pyridoxal-5-phosphate (PLP) Amino group
Pyridoxine-5’-phosphate (PNP)
carbohydrates, requires increased
Pyridoxamine-5’-phosphate (PMP) amounts of B vitamins.
Biotin (B7) Biotin Carboxyl group (carbon
dioxide)
Folate (B9) Tetrahydrofolate Single carbon groups aside
from carbon dioxide

Cobalamine (B12) Methylcobalamin Methyl groups, hydrogen

atom
 Oily fish, eggs, and dairy products are good
rines aresources
fortified ofwith the additional information onpresent
the measurement of vitamin A,
vitamin A. In some countries, breakfast cereals of vitamin
and marga- referAvitamin.
inChapter Carotenoids,
developed 37. andcountries.
in The major
Vitamin Bdietary blindness inThiamin
1 (Thiamin)
the world. pyrophosphate
The earliest feature (Fig. 56.3A;
is nightalso known as thiamin
blindness; eraldehyde 3-phosphate and D-xylulose 5-phosphate with
green vegetables, carrots, andtoother yellow red fruits,
rines are fortified with the vitamin. Carotenoids, present carotenoid,
in
are also a source of retinoids, β-carotene,
typically is cleaved
providing up to 25% in intestinal mucosa
Nature, by is
this
Function, aand diphosphate)
reversible,
Sources but the other is aocular cofactor in several are
manifestations enzyme-catalyzed
not. erythrose 4-phosphate to form fructose 6-phosphate and
green vegetables, carrots, and other yellow and red dioxygenase fruits, Vitamin B 1 (Thiamin)
of vitamin A in developed to countries.
form retinal, whichdietary can be reduced topyrophosphate
retinol.
Decreased(Fig. reactions,
mucin including
secretion causes the conversion ofcharacter-
xerophthalmia, pyruvate to acetyl- glyceraldehyde 3-phosphate. It also has a role in the catabo-
are also a source of retinoids, typically providing up to 25% Nature, Function,The andmajor
Sources Thiamin 56.3A; also known as thiamin
of vitamin A in developed countries. The major dietary
β-carotene, is
carotenoid, However, the recovery
cleaved
Thiamin of retinol
in intestinal
pyrophosphate (Fig.is56.3A;
mucosa incomplete,
by a also known and
diphosphate) 6 μg
as thiaminizedis ofabycofactor CoA in (pyruvate
keratinizing several dehydrogenase
metaplasia complex),
enzyme-catalyzed
squamous 2-oxoglutarate
of the conjunc- lismtoof branched chain amino acids and is involved in the
carotenoid, β-carotene, is cleaved in intestinal mucosadioxygenase to form
carotene
by a retinal, which
isdiphosphate) can
equivalent isto aonly be reduced 1 μg inof several
cofactorto retinol. reactions,
retinol.enzyme-catalyzed including the
tivae, leading conversion
succinyl-CoA of pyruvate
to the formation to
(2-oxoglutarateacetyl-
of areas ofdehydrogenase
white, thickened complex),synthesis
and of acetylcholine and γ-aminobutyric acid.49
dioxygenase to form retinal, which can beHowever, reduced tothe recovery ofreactions,
retinol. retinol isincluding
incomplete, the and 6 μg of of pyruvate
conversion CoA (pyruvate
to acetyl- dehydrogenase two complex),
reactions 2-oxoglutarate
in the pentose to phosphate pathway catalyzed
carotene is equivalent toCoA 1 μg of retinol.
only (pyruvate epithelium
succinyl-CoA (2-oxoglutarate (Bitot spots). Similar
dehydrogenase complex), and changes in the cornea lead Thiamin is essential for the metabolism of all living organ-
However, the recovery of retinol is incomplete, and μg of
6Deficiency and Toxicity dehydrogenase complex), 2-oxoglutarate to byand transketolase: -xylulose 5-phosphate
Dcatalyzed with D-ribose
carotene is equivalent to only 1 μg of retinol. succinyl-CoA (2-oxoglutarate dehydrogenase reactionsto
twocomplex), andinsoftening
the pentose ulceration
phosphate pathway(keratomalacia), which, both isms but is synthesized only in plants, bacteria, and fungi.
Deficiency Vitaminand Toxicity Atwo deficiency
reactions is in the
the commonest
pentose phosphate preventable cause
by transketolase:
pathway of D-xylulose
directly
catalyzed and5-phosphate
indirectly
5-phosphate to with
through formD-ribose
sedoheptuloseto7-phosphate
predisposing infection, and The glyc-best sources of the vitamin are wheat germ and the outer
Deficiency and Toxicity blindness
Vitamin A deficiency in
by the
is the world. preventable
commonest
transketolase: The earliest
D-xylulose causefeature
of is 5-phosphate
5-phosphate night
with blindness; to formblindness.
cause
D-ribose eraldehyde
sedoheptulose Other 3-phosphate
7-phosphate
less dramatic and glyc- and D-xylulose include
manifestations 5-phosphate parts withof other grains (thiamin deficiency used to be common
Vitamin A deficiency is the commonest preventable blindness in the world.
this
cause of The
is reversible, earliest
5-phosphate but feature
theform
to is night
other blindness;
ocular
sedoheptulose eraldehyde
manifestations
7-phosphate andare 3-phosphate
not.
glyc- and D-xylulose
erythrose 5-phosphate with
4-phosphate toparticularly
form fructose 6-phosphateinand
increased susceptibility to infections, respiratory, areas where rice is the staple and was consumed as polished
blindness in the world. The earliest featurethis is reversible,
is night blindness;
Decreasedbut the eraldehyde
other ocular3-phosphate
mucin manifestations
secretion andare
causes not.
D-xylulose
xerophthalmia, erythrose 4-phosphate
5-phosphate with
character- to form fructose 6-phosphate and
this is reversible, but the other ocular manifestationsDecreased mucin are not.secretion causes xerophthalmia,
erythrose 4-phosphate to character- glyceraldehyde
form fructose 6-phosphate presumed
and 3-phosphate. toglyceraldehyde
be related
It also has ato role the3-phosphate.
in decreased
It also has a role in the catabo-
the catabo- mucin secretion. The rice, ie, with the husk removed), yeast, and eggs. The recom-
Decreased mucin secretion causes xerophthalmia, ized by squamous
ized by keratinizing
character- keratinizing metaplasia
glyceraldehyde squamous metaplasia
of the conjunc-
3-phosphate. It also has a role of the
lismin conjunc-
ofthebranchedabsorption
catabo- chain amino lism of branched
of vitamin
acids and A isfrom chain
the gut
involved in amino
requires
the acids
theand is involved in
formation the daily intake is not less than 1.4 mg, the requirement
mended
ized by keratinizing squamous metaplasia tivae, leading
of the tivae,
to theleading
conjunc- lism to
formation of ofthe formation
areas
branched ofchain
white, of areas
thickened
amino acids andof white,
issynthesis
involved thickenedofthemixed micelles,
ofinacetylcholine synthesis
and andof aacetylcholine
γ-aminobutyric acid.49
functional and γ-aminobutyric
deficiency may occur acid.in
49
being higher with carbohydrate-rich than fat-rich diets and
Structure, Function & Metabolism of Water-Soluble Vitamins epithelium (Bitot changes
spots). inSimilar γ-aminobutyric
andchanges lead in the corneaissevere
49
tivae, leading to the formation of areas of epithelium (Bitot
white, thickened spots).synthesis
Similar of acetylcholinethe cornea Thiamin
acid. lead malabsorption
essential Thiamindespite
for the metabolism isofessential
all living for the metabolism
organ-
an adequate dietary supplyof allofliving organ-
in men compared with women. The body’s stores of thiamin
epithelium (Bitot spots). Similar changesto in softening
the cornea toandlead ulceration
softening Thiamin
and is essential for
(keratomalacia),
ulceration the metabolism
which, both
(keratomalacia), of allwhich,
isms living
but isorgan-synthesized
both only
isms in plants,
but isbacteria,
synthesized and fungi.only in plants, bacteria, and fungi.
to softening and ulceration (keratomalacia), directlywhich, both
and indirectly isms
through but predisposing
is synthesized to only in plants, bacteria,
infection, The best and the
fungi.
sources vitamin.
of the vitamin are wheat germ and the outer are more limited than those of most other vitamins, and
directly and indirectly through predisposing cause to
directly
infection,
blindness.
and
Other less
indirectly
Thedramatic
best sources ofthrough
the vitamin
manifestations
predisposing
are wheat germ
include
toof infection,
partsand the
other outer Vitamin
grains (thiamin
The best
toxicsources
A isdeficiency inused
excess; of the
to beacute
common
vitamin
ingestionare wheat
of largegerm
quan- and the manifestations
outer of deficiency may arise within 30 days of
cause blindness. Other less dramatic manifestations cause
include
increased susceptibility blindness.
toparts Other less
of otherparticularly
infections, dramatic
grains (thiamin manifestations
deficiency used
respiratory, to be where
in areas include
common tities
rice iscan parts of
causeandraised
the staple other grains
intracranial
was consumed (thiamin deficiency used
pressure, with headache,
as polished to be common
inadequate intake. Cases of acute clinical thiamin deficiency
increased susceptibility to infections, particularly presumed toincreasedbe related tosusceptibility
respiratory, in areas where
the decreased mucin to infections,
rice is the staple and
secretion. The particularly
was consumed
rice, ie,respiratory,
as polished
with nausea, andinvomiting.
the husk removed), areas where
yeast, riceThe
andChronic
eggs. is the staple and
recom-
excessive was consumed
intake can cause as polished have been reported in starved individuals refed with a high
B-Complex Vitamins
presumed to be related to the decreased mucin secretion.
absorption of The
vitamin
presumed A rice,
from
to beie,the
with
gutthe
related husk
requires
to theremoved),
the formation
decreased yeast, and mended
mucin eggs. Thedaily
secretion. recom- intake
The is not rice, less than 1.4 mg,
ie, with thethehuskrequirement
removed), yeast, and eggs. The recom-
absorption of vitamin A from the gut requires the formation
of mixed micelles, and a mended
functional daily intake is not
deficiency may less
occurthanin1.4 mg,being the requirement
higher with carbohydrate-rich than fat-rich diets and
of mixed micelles, and a functional deficiency absorption of vitamin A from the gut requires the formation mended daily intake is not less than 1.4 mg, the requirement
severemay occur
malabsorption in being
despite anhigher
adequatewith carbohydrate-rich
dietary supply of than fat-rich diets and with women.
in men compared The body’s stores of thiamin
severe malabsorption despite an adequatethe dietary
vitamin. of mixed
supply of micelles,
in men compared and a with functional
women. The deficiency
body’s are may
stores
more of occur
limitedinthan those
thiamin being higher
of most otherwith
H carbohydrate-rich
vitamins, and H than fat-rich diets and
severe malabsorption despite an adequate dietary supply of in men compared N
the vitamin. are more limited
Vitamin A is toxic in excess; acute ingestion of large quan- than those of most other vitamins, and
manifestations of deficiency may arise O with
within 30 days women.
of OThe body’s stores of thiamin
Vitamin A is toxic in excess; acute ingestion tities ofcan
large quan-
the
cause vitamin.
raised manifestations
intracranial of deficiency
pressure, may arise within
with headache, inadequate30 days of Cases ofare
intake. acutemore
clinicallimited
thiaminthan those of most other
deficiency H vitamins, and
B (Thiamin)
tities can cause raised intracranial pressure, with headache,
1
nausea, and vomiting.
nausea, and vomiting.
Chronic excessive intake can cause VitaminChronic B (Riboflavin)
inadequate intake. Cases of acute clinical thiamin deficiency
A isbeen
have
excessive
toxic intake acute
2 excess;
in
reported
can cause ingestion
in starved individuals
have
refed B (Niacin/Nicotinic Acid)
of been
large reported in starved
with a quan-high 3 individuals refed
manifestations of with
deficiency
H
B (Pantothenic Acid)
a high may arise Owithin 30 days of 5 O
tities can cause raised intracranial pressure, with headache, inadequate intake. Cases of acute O clinical thiamin deficiency HO
S
nausea, and H vomiting. Chronic H
excessive intake can cause have been reported in starved individuals refed with a high C Nicotinic acid
H H N H
O
O NO + O
O
H H N
O
Structure

N N
O H
O O
H O H H O H
O HO NN H
S
O S O HO O
C Nicotinic
H acid H C Nicotinic acid N N O
H H
+ O + O H N N O H
N N
O O N O H
N N O
H
N N H H
O O O H HO O O O
N N S H H
N
H
N N
O H
H
N A O Thiamin
C Nicotinic acid B Riboflavin D Pantothenic acid
N N H H
H N
N
H N
NH
O
+ O H O FIGURE 56.3 Thiamin (A), riboflavin (B), nicotinic acid (C), and pantothenic acid (D).
O H N O
H O O N N O O O
A Thiamin B Riboflavin A ThiaminD BPantothenic acid
Riboflavin D Pantothenic acid O H
Its active form TPP acts as a FIGURE 56.3 Thiamin (A), riboflavin (B), nicotinic Coenzyme in oxidoreductase
FIGURE acid56.3
(C), and Coenzyme in oxidoreductase
pantothenic
Thiamin
N acid (D).
(A), riboflavin (B), nicotinic acid (C), and pantothenic acid (D).
H
N Downloaded for Gita Soraya (gsoraya@student.unimelb.edu.au)
Is a component of coenzyme A,
N O
coenzyme in pyruvate reactions: constituent of FAD reactions: the active form NAD involved in numerous metabolic
at The University of Melbourne from ClinicalKey.com.au by Elsevier on July 11, 2019.
H N N H O For personal use only. No other uses withoutH + permission. Copyright ©2019. Elsevier Inc. All rights reserved.
N H
dehydrogenaseDownloaded for Gita Soraya (gsoraya@student.unimelb.edu.au)
Downloaded
and FMD which act as electron
at The University of Melbourne
for Gita Soraya
For personal use only. No other uses without permission. Copyright involved in electron transfer, and
H Inc. All rights reserved.
from ClinicalKey.com.au by at
(gsoraya@student.unimelb.edu.au)
©2019.
For personal useElsevier
only. No
Elsevier on July 11,
The University of2019. O
Melbourne from ClinicalKey.com.au by Elsevier on July 11, 2019.
other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
O pathways
O
A Thiamin B D
carriers in the TCA (Krebs) cycle NADP as a reducing agent in Riboflavin + Pantothenic acid
FIGURE 56.3 Thiamin (A), riboflavin (B), nicotinic acid (C), and pantothenic acid (D).
Role in oxidative and electron transport chain synthetic pathways
Function

decarboxylation of β-
ketoglutarate and also in the ConversionForof retinol tootherretinoic
Downloaded for Gita Soraya (gsoraya@student.unimelb.edu.au) at The University of Melbourne from ClinicalKey.com.au by Elsevier on July 11, 2019.
personal use only. No uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.

metabolism of branched-chain acid

amino acids.
Conversion of tryptophan to
Role in synthesis of GABA and niacin
acetylcholine(neurotransmitters)

Burtis CA, Bruns DE. 2014. Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics. Elsevier Health Sciences.

deficiency are Hartnup disease (in which there is a defect in
the absorption of tryptophan from the gut) and the carcinoid
syndrome (in which diversion of tryptophan to the synthesis
of 5-hydroxytryptamine reduces the amount available for
nicotinic acid synthesis).54
Nicotinic acid (but not nicotinamide) has a role in the
management of dyslipidemias, the basis of which is uncon-
nected with its function as a vitamin.55 It acts at various points
in lipid metabolism with a net effect of modestly reducing
plasma LDL cholesterol concentration and increasing HDL
cholesterol concentration and is used as a secondary agent
to be used with statins in the management of hypercholes-
Structure, Function & Metabolism
terolemia and as a first-line agent in the treatment of hyper-
triglyceridemia. Its acceptability to patients is limited by its
tendency to cause flushing in the doses used therapeutically
(which are far higher than normal requirements), a problem
that has to some extent been ameliorated by combining it
B-Complex Vitamins
with other agents selected to prevent this side effect.
Deficiency and Toxicity
The classic disease of nicotinic acid deficiency is pellagra
(remembered by generations of doctors as the “four B6 (Pyridoxine)
Ds”—
dermatitis, diarrhea, dementia, and death). As alluded to
earlier, it is particularly associated with areas where maize
is the staple food,Vitamin B6 consists
but it can occur of countries
in developed three substituted
as
part of generalized malnutrition and inpyridoxamine
chronic alcoholism. and pyridoxal
Structure
Vitamin B5 (Pantothenic Acid) and supplementation is required in patients treated with Assessment of Status
them.61,62 There is no evidence that a high dietary intake of Biotin status can be assessed by meas
Nature, Function, and Sources pyridoxine is harmful, but high doses of supplements may CoA activity in lymphocytes, the urina
Pantothenic acid (see Fig. 56.3D) is a component of coen- cause a peripheral sensory neuropathy. Various upper limits (both decreased in deficiency), or the
zyme A and thus is involved in numerous essential metabolic for daily intake have been recommended; in the United States, 3-hydroxyisovaleric acid (increased) (s
pathways. A pantothenic acid derivative is required for the it is 100 mg.
activity of acyl-carrier protein, an enzyme involved in fatty Vitamin B9 (Folic Acid, Vitamin M)
acid synthesis.57 Pantothenic acid is widely available in food- Assessment of Status Nature, Function, and Sources
stuffs, including cereals, meat, egg yolk, milk, and vegetables. The various forms of the vitamin can be measured in Folic acid (pteroyl L-glutamic acid) is
The recommended daily intake is 5 mg. plasma using liquid chromatography–mass spectrometry. of a group of substances that have
The normal plasma concentration of pyridoxal phosphate, variety of metabolic processes, notably
Deficiency and Toxicity the major circulating form, is 7 to 52 mg/L in men and and methionine metabolism. The prin
Isolated, spontaneous deficiency of pantothenic acid has not 2 to 26 mg/L in women. Further details are provided in ring folates are tetrahydrofolate (THF
ofbeenWater-Soluble Vitamins
unequivocally described although experimental defi-
Chapter 37. 10-formyl THF, all of which contain
glutamate residues (Fig. 56.6). The m
ciency leads to fatigue, apathy, and numbness and painful Vitamin B7 (Biotin, Vitamin H) is 5-methyl THF. Folic acid per se com
paresthesia (“burning heels”). Toxicity has not been described. Nature, Function, and Sources normal dietary folate intake. The maj
Biotin (Fig. 56.5) is essential for several single-carbon green leafy vegetables, yeast, and nut
Assessment of Status daily intake is 400 μg. Normal body sto
transfer reactions. The reactions have two stages, first the
Pantothenic acid can be measured in plasma by bacteriologic ATP-dependent carboxylation of a biotin prosthetic group 10 mg, so the clinical consequences o
assay (see Chapter 37), but in practice, this is rarely required to form N-1’-carboxybiotin followed by carboxylation of the become manifest for several weeks.
in a clinical setting. substrate (eg, pyruvate carboxylase; pyruvate → oxaloacetate) Folate derivatives can act as both a si
and acetyl Co-A carboxylase (acetyl Co-A → malonyl CoA).63 purine, thymine, and glycine synthesis
Vitamin B6 (Pyridoxine) The first is a B 7 (Biotin
step / Vitamin
in gluconeogenesis and anH) anaplerotic of homocysteine to methionine) and
Nature, Function, and Sources reaction that sustains the tricarboxylic acid cycle; the second of serine to glycine and breakdown of
Three interconvertible compounds have vitamin B6 activ- Its role in purine and thymine synthe
pyridines:
ity: pyridoxine pyridoxal,
phosphate, pyridoxamine phosphate, and O H essential for the synthesis of DNA an
56.4).58 Pyridoxal phosphate O the major effect of deficiency, a mega
pyridoxinephosphate (Fig.
Chapter 72).67

CHO CH2OH CH2NH2 Deficiency

Folate deficiency can arise as a result o
HO CH2OH HO CH2OH HO CH2OH H H malabsorption, increased utilization (
N lytic anemias) or loss (eg, dialysis, infl
O S dermatoses), or the use of certain d
H3C N H 3C N H 3C N methotrexate, and trimethoprim are
N
phenytoin can decrease the intestinal
Pyridoxal Pyridoxine Pyridoxamine H H and ethanol both decreases absorption
FIGURE 56.5 Biotin. tion. (Macrocytosis is a frequent findi
O O O
CHO CH2OH CH2NH2
The active
HO form of CH vitamin
2OPO
– B6, HO pyridoxalCH phosphate
2OPO
– HOand pyridoxamine
CH2OPO–
Downloaded for Gita Soraya (gsoraya@student.unimelb.edu.au) at The University of Melbourne from ClinicalKey.com.au by Elsevier
Biotin is a coenzyme within Formultienzyme complexes responsible
personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
is the most important coenzyme in the amino acid metabolism:
O– O– O– for carboxylation reactions in lipogenesis and gluconeogenesis and in
involved
H 3C N in conversionH3reactions
C N such as transamination,
H 3C N
Function

the catabolism of the branched-chain amino acids

decarboxylation,
Pyridoxal 5-phosphate
dehydrogenations.
Pyridoxine 5-phosphate Pyridoxamine 5-phosphate
It is56.4
FIGURE alsoStructures
involvedof thein carbohydrate
various forms of vitamin Band
. (Fromlipid metabolism
Marshall WJ, Lapsley M, Day AP,
6
Ayling RM. Clinical biochemistry: Metabolic and Clinical Aspects. 3rd ed. Edinburgh: Elsevier; 2014.) Can be synthesized by gut flora
Pyridoxine is involved in the synthesis of neurotransmitters (serotonin
and adrenaline),
Downloaded for Gita Soraya (gsoraya@student.unimelb.edu.au) at The sphingosine, heme
University of Melbourne from ClinicalKey.com.au by Elsevier on July 11, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.

Burtis CA, Bruns DE. 2014. Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics. Elsevier Health Sciences.
Structure, Function & Metabolism of Water-Soluble Vitamins

B-Complex Vitamins
B9 (Folic Acid) Vitamin B12

One of the most complex

low-molecular-weight substances
Structure

A cobalamin structure
(contains cobalt tetrapyrrole)

Coenzyme in single-carbon transfer reactions:

• Synthesis of nucleic acid
Coenzyme in single-carbon transfer reactions: • Erythrocyte production
• Methylation (important for gene expression and metabolism) • Metabolism of folic acid
Function

• Synthesis of serine, glycine, choline, methionine

• Synthesis of purine and pyrimidine (nucleic acid) Involved in rearrangement reactions. For example, they act as
coenzymes in the conversion of methylmalonyl-CoA to succinyl-CoA
Active forms: tetrahydrofolate, 5-methyl tetrahydrofolate (N 5 MeTHF) and in the formation of methionine from homocysteine
and N 10 -formyltetrahydrofolate-polyglutamate
Synthesized solely by bacteria. It is found only in animals, and is
absent in all plant. Its absorption requires intrinsic factor (IF)
Burtis CA, Bruns DE. 2014. Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics. Elsevier Health Sciences.
Structure, Function & Metabolism of Water-Soluble Vitamins

Vitamin C (Ascorbic Acid)

Vitamin C functions as electron donor (reducing agent)

in several enzymatic reactions involved in the synthesis of
collagen, carnitine, and monoamine neurotransmitters

Antioxidant and scavenger of free radicals

Facilitates intestinal absorption of iron

Hyper- and Hypo-vitaminosis of Lipid-Soluble Vitamins

No toxicity reported Peripheral

No toxicity reported Hepatotoxicity No toxicity reported
neuropathy

Vitamin B1 Vitamin B2 Vitamin B3 Vitamin B5 Vitamin B6

Beri-Beri (peripheral nerve Angular stomatitis: Pellagra (4 Ds): No cases reported Neurologic
damage): inflamed corners of the Dermatitis, symptoms: irritability,
Dry – peripheral neuropathy mouth Dementia depression,
and muscle weakness Diarrhea convulsions
Wet – additional edema Glossitis: inflamed Death
x failure
and heart tongue Sideroblastic
x anemia:
characterized by the
Wernicke-Korsakoff presence of nucleated
Syndrome (CNS lesion): red blood cells with
acute encephalopathy iron granules
followed by chronic
psychosis
 Hyper- and Hypo-vitaminosis of Water-Soluble Vitamins

Peripheral neuropathy No toxicity reported Toxicity uncommon Indigestion, diarrhea

Vitamin B7 Vitamin B9 Vitamin B12 Vitamin C

Regular consumption of raw egg In pregnancy, deficiency causes Pernicious anemia: Scurvy:
(contains avidin which binds to fetal neural tube defects. Megaloblastic anemia with Perifollicular hemorrhages,
biotin) can cause deficiency spinal cord degeneration hemorrhage from mucous
(alopecia, dermatitis, conjungtivitis). Megaloblastic anemia: the membranes, poor wound
Cook eggs to denature avidin. presence of enlarged blast cells Neuropathy healing, behavioural changes
x in the bone marrow
Subclinical maternal deficiency Behavioral changes
causes congenital malformations Neuropathy
Minerals – Learning Objectives

1 Definition and classification of minerals

2 Daily requirements and sources of minerals

3 Structure, function, and metabolism of the minerals

4 Consequences and manifestations of mineral excess and deficiencies

Definition and Classification of Minerals

Minerals Definition

Minerals are inorganic nutrients which serve

numerous biochemical and physiological functions.
The organism is incapable of producing most Minerals
minerals on its own

Macrominerals Microminerals

Minerals Classification Required in large Required in small

amounts amounts (<100
Based on the amount we require, minerals are (>100 mg/day) mg/day)
classified into macrominerals and microminerals
(trace elements)
 Na 100 Table salt 1.1-3.3 membrane potential,
mineral metabolism
Vegetables, fruit, Membrane potential,
K 150 cereals 1.9-5.6 mineral metabolism
Bone formation,
Nutrients 363 Ca 1 300 Milk, milk products 0.8 blood clotting,
signal molecule
Bone formation,
A. Minerals Mg 20 Green vegetables 0.35
cofactor for enzymes

Mineral
Mineral
(g) * Daily Requirement
Content Major source Daily requirement
(g) and Sources
Functions/Occurrence Cl 100 Table salt 1.7-5.1 Mineral metabolism
Bone formation, energy
Meat, milk,
P 650 cereals, vegetables 0.8 metabolism, nucleic
Water 35 000- Drinks 1200 Solvent, cellular buil- acid metabolism
40 000 Water in solid ding block, dielectric, S-containing Lipid and carbohydrate
900 S 200 amino acids 0.2 metabolism,
foods coolant, medium for
From metabolism 300g transport, reaction partner (Cys and Met) conjugate formation

Macroelements (daily requirement >100 mg) Microelements (trace elements) (mg

Osmoregulation, Meat, liver, eggs, Hemoglobin, myoglobin,
membrane potential, Fe 4-5 vegetables, potatoes, 10 cytochromes,
Na 100 Table salt 1.1-3.3
mineral metabolism cereals Fe/S clusters
Zn 2-3 Meat, liver, Zinc enzymes
Vegetables, fruit, Membrane potential, cereals 15
K 150 cereals 1.9-5.6 mineral metabolism
0.02 Found in many Enzymes
Mn foodstuffs 2-5
Bone formation,
Ca 1 300 Milk, milk products 0.8 blood clotting, Meat, vegetables,
Cu 0.1-0.2 2-3 Oxidases
signal molecule fruit, fish
Bone formation, Co <0.01 Meat Traces Vitamin B12
Mg 20 Green vegetables 0.35
cofactor for enzymes
Cr <0.01 0.05-0.2 Not clear
Cl 100 Table salt 1.7-5.1 Mineral metabolism
Cereals, nuts,
Bone formation, energy Mo 0.02 legumes 0.15-0.5 Redox enzymes
Meat, milk,
P 650 cereals, vegetables
0.8 metabolism, nucleic
acid metabolism Se Vegetables, meat 0.05-0.2 Selenium enzymes
S-containing Lipid and carbohydrate
S 200 amino acids 0.2 metabolism, Seafood,
(Cys and Met) conjugate formation I 0.03 iodized salt, 0.15 Thyroxin
drinking water
Microelements (trace elements) (mg Requirement not known Metals Non-metals
Meat, liver, eggs, Hemoglobin, myoglobin, Drinking water
Fe 4-5 vegetables, potatoes, 10 cytochromes, F (fluoridated), tea, milk 0.0015-0.004 Bones, dental enamel
cereals Fe/S clusters
Zn 2-3 Meat, liver,
cereals 15 Zinc enzymes *
Content in the body of a 65 kg adult

Found in many
Mn 0.02 2-5 Enzymes
foodstuffs Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
Koolman J, Röhm KH, Wirth J, & Robertson M. 2005. Color Atlasreserved.
All rights of Biochemistry. Volume
Usage subject 2. Stuttgart:
to terms Thieme.of license.
and conditions
Cu 0.1-0.2 Meat, vegetables, Oxidases
fruit, fish 2-3

Co <0.01 Meat Traces Vitamin B12

Cr <0.01 0.05-0.2 Not clear

Cereals, nuts,
Mo 0.02 legumes 0.15-0.5 Redox enzymes

Se Vegetables, meat 0.05-0.2 Selenium enzymes

Seafood,
 Macromineral
Sodium (Na) and Potassium (K)

Sodium (Na+) and Potassium (K+) are essential cationic

minerals known as electrolytes

Functions:
1. Maintain extracellular osmolality and intracellular
volume
2. Electrophysiological role in maintaining cell membrane
potential and impulse transmission:
• K+ is the main intracellular cation (30x higher than
extracellular levels) Hyper and Hypokalemia can cause
• Na+ is the main extracellular cation (in the cell it is 10x life-threatening arrythmia
higher than K+)
 Calsium homeostasis is controlled by the
Macromineral parathyroid hormone (PTH) and by Calcitriol

PTH:
• PTH excreted when extracellular calcium levels
Calcium (Ca) decrease
• Works on bone (osteolysis), renal (calcium
reabsorption, and increases 1-alfa-hydroxilase
which synthesises vitamin D
Calsium (Ca2+) is the most prevalent mineral in the body
Calcitriol (Vitamin D)
It is mostly in the bone in the form of calcium salt. It can • Cholecalciferol is obtained from diet or 7-
also be found in plasma to perform various biochemical dehydrocholesterol in skin exposed to UV. In
processes: kidneys calcitriol is formed from hydroxylation by
• Muscle contraction 1-alfa-hydroxylase
• Blood coagulation • Calcitriol works with PTH to increase calcium
uptake in gut
• Secondary messenger 8 1 Structure and Function of the Kidney

• Glycogen breakdown and activator of the Krebs Fig. 1.8 PTH action in
response to low serum
cycle calcium (–) Parathyroid
glands
(+)

Low
serum

Deficiency: calcium

• Mostly caused by hypoparathyroidism, vitamin D Calcium PTH

deficiency, dietary deficiency

• Slows bone formation Bone
Activates

• Neuromuscular hyperexcitabilty
vitamin D
Activates osteoclasts Kidney

Stimulates calcium
Findlay M & Isles C. 2015.
reabsorption by tubules Clinical Companion in
Vitamin
Gut D Nephrology. Springer
International Publishing
Stimulates calcium reabsorption by
intestine

Fig. 1.9 The Renin- Angiotensin I

Angiotensin-Aldosterone
system ACE
Renin
Angiotensin II
Direct
vasoconstriction
Low BP (+)
BP
sodium
depletion

Raised BP
 Macromineral
Magnesium (Mg)
Magnesium is an intracellular cation mainly found
in muscle and bone
Function
• As cofactor in > 300 enzyme-catalyzed
reactions, mainly for energi metabolism and
synthesis of nucleic acids or proteins
• Controls transmembrane ion channels and
membrane excitability
Excess
• Rare, because Mg is readily
excreted by kidneys
• Hypermagnesemia often occur in
renal failure
Deficiency
• Mainly caused by over-processing
of food, diuretic use, and alcohol
intake
• Hypermagnesemia often leads to
hypokalemia and hypocalcemia
Symptoms of hypomagnesemia:
weakness, tremor, arrythmia
 Macromineral
Chloride (Cl)

Chloride is the major extracellular anion Function

• Fluid and electrolyte balance
Homeostasis • Production of HCl (gastric juice)
• Absorption from diet in the form of • Transport of CO2 in the blood (chloride
either sodium or potassium chloride shift)
through the small intestine Na+/Cl-
symporter Excess
• Homeostasis of chloride is controlled by Hyperchloremic acidosis
the same mechanism behind sodium
and potassium homeostasis
• Chloride levels often parallel with
sodium levels
 Macromineral
Phosphorus (P)
As much as 85% of phosphorus is found in the bone in
the form of hydroxyapatite crystals [Ca10(PO4)6(OH)2].
The rest is found in soft tissue and extracellular fluid
Deficiency
• Deficiency of phosphate is rare
• Sever hypophosphatemia is dangerous

Physiologic/biochemical function of phosphorus:

• DNA and RNA component Excess
• Secondary messenger (cAMP, IP3) Hyperphosphatemia common in the renally
• Acid-base balance: Na2HPO4) an important H+ impaired patient
buffer
• Hemoglobin transport (2.3-biphosphoglycerate)

Structural function of phosphorus

• Essential component of bone mineral
• Essential component of tooth enamel
• Phospholipids: essential component of cell
membrane
Micromineral 80% of the body’s total iron is classified as
functional iron:
Iron (Fe) • 65% of functional iron is a main
componen of hemoglobin (role in
transport of blood O2)
• 10% of functional iron is in the form of
myoglobin (binding of O2 in muscle)
• 2.5% of functional iron is in the form of
cytochoromes, which plays a role in the
respiratory chain and oxidative
metabolism
• The rest play a role in various key
enzymes

19% of the body’s total iron is non-

functional iron (deposit)

1% of the body’s total iron circulates in

blood bound to transferrin
 Micromineral
Metabolism and Transport of Iron
Iron (Fe) • Iron is obtained from the diet
• Iron is absorbed in the proximal small
intestine, and absorption is enhanced by
ascorbic acid
• Absorbed iron is either deposited in
enterocytes in the form of ferritin (Fe3+),
or transported in plasma by hephaestin
and ferroportin
• Iron is transported in plasma bound to
transferrin
• Iron is utilized by erythroblasts to form
hemoglobin
• Old erythrocytes are destroyed by
macrophages in the reticuloendothelial
system

Baynes JW & Dominiczak MH. 2018. Medical Biochemistry. Elsevier Health Sciences.
 Micromineral Iron deficiency

Occur mostly in children, pregnant and

Iron (Fe) menstruating women, elderly

Deficiency disturbs erythropoiesis, which

Iron excess
results in microcytic and hypochromic anemia
Hemochromacytosis is an autosomal recessive disorder
resulting in increased iron absorption. This results in iron
accumulation in the skin, heart, liver, pancreas.

Hyperpigementation in hemochromacytosis. Source www.merckmanuals.com

 Micromineral
Iodine (I)

Several mountain populations still experience goiter due Iodine is obtained from diet and
to iodine deficiency (endemic goiter) transported to the thyroid gland

Iodine function: synthesis of thyroxine

and triiodothyronine hormones. Both
hormones control the adult basal
metabolic rate and also growth in children

Iodine deficiency
In children it causes goiter and disturbed
growth in children.
In pregnant women it results in dwarfisme
and mental retardation in the child

Eastman CJ, Zimmermann MB. The iodine deficiency disorders. In Endotext [Internet] 2018 Feb 6. MDText.com, Inc.
 Micromineral
Zinc (Zn)

Zinc function: Zinc deficiency:

• Zinc is contained in + 100
metalloenzymes associated with
carbohydrate and energi metabolism,
protein synthesis and degradation,
and nucleic acid synthesis
• Role in immune function, cell division,
and cell growth
• Role in spermatogenesis
• Role in maintenance of skin integrity
and wound healing
• Very common
• In children: growth retardation,
• Skin lesion and delayed wound
healing
• Impaired immune function
Zinc Excess:
May interfere with copper
absorption à copper deficiency
and anemia
 Micromineral
Copper (Cu)

Cu Function:
• As cofactor in enzymatic reactions
• Is a component in several important molecules:
ceruloplasmin, superoxide dismutase, cytochrome
oxidase
• Role as scavenger towards reactive oxygen species

Copper metabolism
• Copper is absorbed in the small intestine, and enters
plasma bound to albumin
• Cu-Albumin complex is taken by liver and forms
apoceruloplasmin (facilitated by ATP7B which is a form
of ATPase) and then released into the circulation
• Copper is excreted in the bile

Baynes JW & Dominiczak MH. 2018. Medical Biochemistry.

Elsevier Health Sciences.
 Micromineral Copper excess:
• Copper can accumulate in tissue
Copper (Cu) • Chronic accumumlation: liver cirrhosis
• Acute accumulation: hemolysis, damage
to liver and brain cells
• Autosomal dominant inherited
Copper deficiency: metabolic defect Wilson's disease: due
to mutations in the gene coding for the
Can occur during reduced intake or excess loss (eg: ATP7B ATPase the liver's capacity to
during renal dialysis) synthesize ceruloplasmin is
compromised. This results in a reduced
Deficiency manifests itself as a microcytic incorporation of copper into
hypochromic anemia resistant to iron therapy ceruloplasmin and in its cellular
accumulation. Copper accumulates in
tissues such as the brain and cornea.
Patients present with neurologic
symptoms or liver cirrhosis and have
typical Kaiser–Fleischer rings in the
cornea
 Micromineral
Selenium (Se), Chromium (Cr)

Selenium is a component of Chromium is a component of the

selenoprotein. Eg: glutation peroxidase, protein chromodulin . Chromodulin
iodothyronine deiodinase (which assists the binding of insulin with
produces the thyroid hormone T3) insulin receptor

Chromium deficiency:
Selenium deficiency: Impaired glucose tolerance due to
• Decline immune function and reduced effectivity of insulin
cognitive problems
• Pain and muscle weakness
• Hair loss
• Causes growth problems in children
 Micromineral
Fluoride (F)
Example of fluorosis (excess fluoride)
Fluoride effects bone structure and tooth
enamel

In the teeth, fluoride increases resistance

towards acids produced by oral bacteria

Excess fluoride causes changes in the

colour of the teeth
 Micromineral
Manganese (Mn) dan Cobalt (Co)

Mangan has an important role in enzyme Cobalt is a component of

activity and is a component of various cobalamin or vitamin B12
metalloenzymes such as oxidoreductase,
hydrolase, mutase, transferase, ligase

Mangan deficiency:
Rare, and usually found in malnutrition.
Symptoms are nonspecific: nausea, dermatitis,
impaired growth of hair and nails.
 References

1. Nelson DL, Lehninger AL & Cox MM. 2008. Lehninger Principles of Biochemistry. Macmillan.
2. Koolman J, Röhm KH, Wirth J, & Robertson M. 2005. Color Atlas of Biochemistry. Volume 2.
Stuttgart: Thieme.
3. Blanco G & Blanco A. 2017. Medical biochemistry. Academic Press.
4. Devlin TM. 2011. Textbook of Biochemistry with Clinical Correlations. John Wiley & Sons.
5. Scanlon VC & Sanders T. 2018. Essentials of Anatomy and Physiology
6. Bender DA & Mayes PA. 2003. Vitamins and Minerals. In: Harper’s Illustrated Biochemistry
26th ed. McGraw-Hill.
7. Satyanarayana U & Chakrapani U. 2013. Biochemistry. Elsevier.
8. Eastman CJ, Zimmermann MB. 2018. The Iodine Deficiency Disorders. InEndotext [Internet]
2018 Feb 6.
9. Baynes JW & Dominiczak MH. 2018. Medical Biochemistry. Elsevier Health Sciences.
10. Brody, T. 1998. Nutritional biochemistry. Elsevier.
11. DeMan JM, Finley JW, Hurst WJ, Lee CY. 1999. Principles of food chemistry, 4th Ed.
Gaithersburg, MD: Aspen Publishers.
12. Burtis CA, Bruns DE. 2014. Tietz Fundamentals of Clinical Chemistry and Molecular
Diagnostics. Elsevier Health Sciences.