VITAMINS,WATER and

MINERALS METABOLISM

By:
SYAHRIJUITA
BIOCHEMISTRY DEPARTMENT,MEDICAL FACULTY
HASANUDDIN UNIVERSITY
September 2014
Topic:
1.VITAMINS : 2.WATER :
Defenition Structure
Water soluble vit Function
Fat soluble vit Metabolism
& Metabolism
3. MINERALS :
Defenition
Classification
Metabolism
OBJECTIVES
1. Can explain about defenition,
structure,function and vitamins
metabolism
2. Can explain about
structure,function and water
metabolism
3. Can explain about
defenition,classification, and minerals
metabolism
all amounts

Defenition:
 Vitamins : essential organic compounds
that the animal organism is not capable of
forming itself, although it requires them in
small amounts for metabolism.
. Vitamin requirements vary from species to species and
are influenced by:
- age
- sex
- physiological conditions such as :
pregnancy, breast-feeding, physical exercise
- nutrition
Classification
Functions:
 Most vitamins are precursors of
coenzymes  water soluble
 Visual process (A)
 Precursors of hormones (D)
 Act as antioxidants (E)
 Coagulation factors (K)
etc
Metabolism of Vitamins
 Metabolism
 A healthy diet usually covers average daily vitamin
requirements.
 By contrast, malnutrition,malnourishment (e. g., an
unbalanced diet in older people, malnourishment in
alcoholics,ready meals), or resorption disturbances
lead to an inadequate supply of vitamins from which
hypovitaminosis,
or in extreme results avitaminosis. Medical
treatments that kill the intestinal flora—
e. g., antibiotics—can also lead to vitamin
deficiencies (K, B12, H) due to the absence of
bacterial vitamin synthesis.
Metabolism
 The causes of vitamin deficiencies can
be treated by improving nutrition and
by administering vitamins in tablet
form.
 An overdose of vitamins only leads to
hypervitaminoses, with toxic
symptoms (vitamins A and D )
 Normally, excess vitamins are rapidly
excreted with the urine.
Structure and Function
VITAMIN A

 The active forming of vitamin A : retinol, retinal, and

asam retinoat.
 β-karoten is precusor vit A from diets
 Retinol : coenzim, synthesis of glycoprotein and
mucopolisacarida.
 Retinal : visual process as retina pigmen  rodopsin.
 Asam retinoat : growth factors
 Vitamin A stored in hepar
 Vitamin A deficiency can result in night blindness, visual
impairment, and growth disturbances.
 Overdoses vitamin A was toxic (hepatospenomegali,
bone pain, vomit, dan diare
 Vitamin D
 Vitamin D (calciol, cholecalciferol) is the precursor of
the hormonecalcitriol (1",25-dihydroxycholecalciferol
 Together with two other hormones (parathyrin and
Calcitonin,) calcitriol regulates the calcium metabolism .
 Calcitriol can be synthesized in the skin from 7-
dehydrocholesterol, an endogenous steroid, by a
photochemical reaction.
 Vitamin D deficiencies only occur when the skin receives
insuficient exposure to ultraviolet light
 vitamin D is lacking in the diet.
 Deficiency is observed in the form of rickets in children and
osteomalacia in adults 
in both cases, bone mineralization is disturbed.
 Vitamin E

 The Actve forming of Vitamin E : alfa

tocopherol
 related compounds only occur in plants
(e. g., wheat germ).
 In the lipid phase, vitamin E is mainly
located in biological membranes,
 as an antioxidant it protects unsaturated
lipids against ROS and other radicals
 Vitamin K
 The active forming of Vitamin K :phylloquinone
and similar substances with modified side chains are
involved in carboxylating
glutamate residues of coagulation factors in the liver
 The form that acts as a cofactor for carboxylase is
derived from the vitamin by enzymatic reduction.
 Vitamin K antagonists (e. g., coumarin derivatives)
inhibit this reduction and consequently carboxylation as
well.
 This fact is used to inhibit blood coagulation in
prophylactic treatment against thrombosis.
 Vitamin K deficiency occurs only rarely, as the
vitamin is formed by bacteria of the intestinal flora.
Structure and Function
 VITAMIN B1

 Vitamin B1 = thiamine
 The aktive forming : tiamin difosfat
coenzim.
 Defisiensi thiamine can results disturbance
of cell energy forming, beri-beri (i
neuropaty, insufisients of hepar, dan atrofi
of muscle
VITAMIN B2
 Vitamin B2 = riboflavin

 prekursor coenzim FMN (flavin mononukleotida)

and FAD (flavin dinukleotida).
 Defisients of vitamin B2 with symptoms:
glossitis, seboroic, stomatitis angularis, cheilosis,
and fotofobia.
VITAMIN B3
 Vitamin B3 = niasin
 prekursor coenzim NAD (nikotinamida adenin
dinukleotida) dan NADP (nikotinamida adenin
dinukleotida fosfat)
 Defisients of vitamin B3 can results skin damage
(pelagra), gastrointestinal distrub, and
depression.
VITAMIN B5
 Vitamin B5 = Panthotenat acid
 Biosinthesis of koenzim A  metabolism of carbohidrat,
fatty acid, and amino acid.
 Defisients of vitamin B5 is rare because easy to take it
from many diet.

VITAMIN B6
 The name is pyridoxin
 The aktive forming is piridoksal fosfat, coenzim for
biosinthesis and catabolism and amino
acid,glycogenolysis.
 Defisients vitamin B6 : rare
 Isoniazid and penicillamin made complex relationships
with B6,  results defisients.
VITAMIN B12

 The name =cobalamin.

 Only synthesis by mikroorganisma,  found only
animals diets and not from plants.
 Defisients ofvitamin B12 can results anemia
pernisiosa.

VITAMIN H
 The name = Biotin.
 coenzim for carboksilation reaction (exp; asetil KoA
karboksilase → lipogenesis)
 Found in many diets and can be synthesis by
intestinal bacteria
 Defisients is rare, but can results from long antibiotic
therapy and consumption of many original egg 
avidin
 FOLAT

 As anion of folat acid, Formed by one derivat pteridin, 4-

amino benzoat, and glutamat acid.
 Reduction of folat can results tetrahidrofolat  coenzym
C1 metabolism (biysinthesis serin, metionin, cholin,
glysin, and nucleotida purin)
 Defisients of folat is often occurdisturbance of
gangguanabolism nucleat acid and lipid metabolism
 Defisients of folat often made anemia megaloblastic
 Intake folat must increase at pregnant trimester 2 and 3
because in this fase, there increased blood cells
proliferat.ion
VITAMIN C

 Vitamin C = ascorbat acid

 Needed as coenzim for biosynthesis of colagen
 ( protein connecting). The collagen is the basic
substance of matrixextracelluler and bone .
 Tyrosine degradation, catecholamine synthesis, and
bile acid biosynthesis
 Vitamin C is an important antioxidant like vitamin E
 Defisiense of vitamin C can results scorbut (scurvy).
 Scurvy is characterized by easily bruised skin, muscle
fatigue, soft swollen gums, decreased wound healing
and hemorrhaging, osteoporosis, and anemia
Structure Of Water
The water molecule :
 is a irreguler

 has tetrahedran with

oxygen at its center

 The 105 degree angle
between the hidrogens
 Forms Hidrogens bonds
The Functions of Water
 Water is an ideal biologic solven
 Influences the structure of biomolecule
 stabilizer
 Water is an excellent nucleophile
Water Steady State
Amount Ingested = Amount Eliminated

Pathological losses:
vascular bleeding (H20,
Na+)
vomiting (H20, H+)
diarrhea (H20, HCO3-).
Body Fluids and
Fluid Compartments

 The percentage of total body water: 45-75%

 Intracellular compartment
 2/3 of body water (40% body weight)
 Extracellular compartment
 1/3 of body water (20% body weight)
 the blood plasma (water=4.5% body weight)
 interstitial fluid and lymph (water=15% body
weight)
 transcellular fluids: e.g. cerebrospinal fluid,
aqueous humor (1.5% BW).
The normal composition of the major body fluid
compartments is approximately as follows
(mmol/l, except Ca2+)

Constituent Plasma Intestitial Fluid Intracellular Fluid

Na 142 145 12
K 4 4,1 150
Ca 1–2 1–2 <10 mol/L*
Mg 0,75 – 1,5 2
Cl 103 113 4
HCO3 25 27 12
Protein 60 25

* Free ionic Ca2+ is very low inside cells, total calcium may be
much higher (1-2mmol/l)
Body Water Distribution
•Individual variability (lean body mass)
–55 - 60% of body weight in adult males
Input
–50 - 55% of body weight in adult female
–~42 L For a 70 Kg man.

RBC PLASMA WATER

ECF
5% 3L
20% 14 L
CELL WATER INTERSTITIAL
40% 28 L FLUID
COMPARTMENT
15% 10 L
TRANSCELLULAR WATER

1% 1L
Body Fluid and Electrolyte Balance

• Water input and output

 The role of the kidneys in maintaining
balance of water and electrolytes
The regulation of body water balance
 thirst sensation
 control of renal water excretion by ADH
 Defenition of Minerals

Inorganic elemental atoms that are essential nutrients.

Not changed by digestion or metabolism.
 Functions of Minerals
 Some participate with enzymes in
metabolic processes (cofactors)
 Some have structural functions (Ca, P in
bone; S in keratin)
 Acid-base and water balance (Na, K, Cl)
 Nerve & muscle function (Ca, Na, K)
 Unique functions (e.g., heme, B12,
thyroid hormones)
Classification
 Macro or Major minerals  Micro or Trace minerals
 Sodium, potassium, (body needs relatively
magnesium, calcium, less)
phosphorus, sulfur,  Chromium, manganese,
chloride iron, cobalt,
molybdenum, copper,
zinc, fluoride, iodine,
selenium, silicon, tin,
arsenic, nickel…
 Present in body tissues  Present in body tissues
at concentrations >50 at concentrations <50
mg/kg (50 ppm) or
mg/kg (50 ppm) or
 Needed < 100 mg/d
 Needed > 100 mg/d
Nutritionally Important Minerals
Macro Trace
Element g/kg Element mg/kg

Ca 15 Fe 20-50
P 10 Zn 10-50
K 2 Cu 1-5
Na 1.6 Mo 1-4
Cl 1.1 Se 1-2
S 1.5 I 0.3-0.6
Mg 0.4 Mn 0.2-0.5
Co 0.02-0.1
Minerals in Foods
 Found in all food groups.
 More reliably found in
animal products.
 Often other substances in
foods decrease absorption
(bioavailability) of minerals
 Oxalate, found in spinach,
prevents absorption of most
calcium in spinach.
 Phytate, form of phosphorous
in most plants makes it poorly
available
Mineral Interactions
Factors Affecting Requirements
 Physiological state/level of production
 Interactions with other minerals
 Tissue storage
 Form fed
 inorganic vs organic forms
 Na selenite vs Na selenate vs selenomethionine
Deficiencies and Excesses
 Most minerals have an optimal range
 Below leads to deficiency symptoms
 Above leads to toxicity symptoms
 Mineral content of soils dictates mineral
status of plants (i.e., feeds)
 May take many months to develop
 Time impacted by body stores
Requirements and Toxicities
Element Species Requirement, Toxic level,
mg/kg mg/kg
Cu Cattle 5-8 115
Swine 6 250
Co Cattle 0.06 60

I Livestock 0.1 ?

Se Cattle 0.1 3-4

Horses 0.1 5-40
The Major Minerals: an Overview
 Macrominerals
 Needed in > 100 mg/d
 Calcium
 Phosphorus
 Magnesium
 Sodium
 Chloride
 Potassium
Bioavailability, & Regulation of
Major Minerals
 Bioavailability
 Influenced by genetics, aging, nutritional status &
other food compounds
 Absorption
 Small intestine & large intestine
 Regulation
 Kidneys & small intestine
Calcium
 Most abundant mineral
in animal tissues
 99% Ca in skeleton
 Present in:
 Blood & other tissues
 Lots of functions
 Bone structure
 Nerve function
 Blood clotting
 Muscle contraction
 Cellular metabolism
 Calcium
 Both Ca and P are required for bone
formation and other non-skeletal functions
 Dietary ratio of 1:1 to 2:1 is good for most
animals (exception is laying hen, 13:1;
Ca:nonphytate phosphorous)
Calcium Absorption
 Dependent on Vitamin D
 Ca binding protein in intestinal epithelial cell
 Absorption depends on need
 Particularly high during growth, pregnancy and
lactation
 Bioavailability decreased by
 Phytates (grains)
 Oxalates
 Wheat bran
 Low estrogen levels (postmenopausal women)
 Calcium Regulation
 Plasma Ca is regulated variable
 Normal plasma concentration is 8-12 mg/dl
 Calcium Regulation
 Three hormones involved in regulation
 Vitamin D3
 from kidney
 Parathyroid hormone (PTH)
 from parathyroid gland
 Calcitonin
 from thyroid gland
 PTH and Vitamin D3 act to increase plasma Ca,
while calcitonin acts to decrease plasma Ca
Responses to Low Blood Calcium
 Parathyroid hormone (PTH) released
 Stimulates conversion of inactive form of
vitamin D to calcitrol
 Increases in blood calcium
 Small intestine
 Resorption at kidneys & blood
Regulation of
Calcium
Homeostasis
 Calcium Deficiencies
 Rickets
 in growing animals
 Osteomalacia (osteoporosis)
 in adult animals
 Milk fever (parturient paresis)
 in lactating animals
Calcium and Bone Health
 Bone growth is
greatest during
“linear growth”
 Peaks out at around
age 30
 Calcium in bones
used as reservoir for
other needs.
 Maintains blood
calcium homeostasis
Calcium and Osteoporosis
 Around age 40,
bone breakdown
exceeds formation.
 Ideally, want very
high bone mass
when this begins.
 By age 65, some
women have lost
50% of bone mass.
Prevention is the Key
 Maintain adequate
calcium and vitamin D
intake—many
recommend
supplements?
 Most are absorbed
similarly
 Costs vary widely
 What’s wrong with dairy
products?
 Perform weight-bearing
exercise
 Take estrogen
supplements?
Structural Functions of Calcium:
Bones & Teeth
 Bones
 Osteoblasts
 Bone formation
 Osteoclasts
 Breakdown of older bone
 Hydroxyapatite
 Large crystal-like molecule
Regulatory Functions of Calcium
 Stimulates blood clotting
 Muscle contractions
 Transmission of nerve impulses
 Vision
 Regulation of blood glucose
 Cell differentiation
 Cofactor for energy metabolism
Focus on Foods: Milk, Calcium, &
Chronic Disease
 Associations of reduced risk of chronic
disease:
 Degenerative diseases
 Heart disease
 Lowers blood pressure
 Cancer
 Breast, prostate, colon
 Obesity
Calcium Toxicity
 Deposition in soft tissue

 Impaired kidney function

 Interference of other nutrient

absorption
 Iron & zinc
Phosphorous
 Functions
 Similar to calcium
 Vitally important in energy metabolism
 ATP
 sugar phosphates
 Phosphoproteins
 Deficiencies include
 Rickets or osteomalacia
 Pica (depraved appetite) – chewing of wood,
bones
 Low fertility and poor milk production or growth?
Phosphorous
 Impact on environment has scientists
revisiting nutritional requirements
 Requirements are being lowered without
any negative effects on reproduction or
milk production
 Bioavailability could be improved if
phytate P can be reduced
 Main source of P in grain
Phosphorus (P)
 Component of cell membranes & walls
 Found in all foods
 Structural & functional roles in body
 Energy metabolism
Metabolism & Regulation of
Phosphorus in the Body
 Small intestine
 Vitamin D-dependent active transport
 Simple diffusion

 Concentrations controlled by:

 Calcitriol, PTH, calcitonin
Functions of Phosphorus
 Phospholipids
 Component of:
 DNA & RNA
 ATP
 Protein synthesis
 Energy metabolism
 Maintenance of blood pH
 Forms hydroxyapatite
Phosphorus Toxicity
 Mineralization of soft tissues
Sodium
 Absolutely an essential nutrient, but has been
“demonized” like cholesterol.
 Typical intakes way higher than what is
needed in humans; added to livestock diets.
 Body usually gets rid of excess quite easily.
 Functions
 Acid-base and osmotic balance of body fluids
 Major cation of extracellular fluid
 Nerve transmission
 Transport and absorption of sugars and amino acids
Sodium and Health
 High blood sodium is
associated with high
blood pressure and
risk of heart disease
 However, high blood
sodium rarely due to
dietary excess.
 Again, genetics and
other factors are
involved.
Sodium & Chloride
 Commonly found together in foods

 Join via ionic bonds to form salt

 Added freely to foods during:

 Processing
 Cooking
 A meal
Did you know…
 Salt free means:
 Less than 5 mg sodium/serving

 Very low salt means:

 Less than 35 mg sodium/serving

 Low salt
 Less than 140 mg sodium/serving
Dietary Sources & Bioavailability
 Table salt
 Monosodium glutamate
 Highly processed foods
 Condiments
 Some meats, dairy products, poultry &
seafood
 Bioavailability
 Affected by malabsorption
Regulation of Sodium & Chloride
in the Body
 Small intestine
 Sodium absorbed first
 Chloride second
 Sodium
 Absorbed with glucose
 Also actively absorbed in colon
 Water absorption
Regulation of Sodium in Blood
Functions of Sodium & Chloride
 Electrolytes
 Fluid balance
 Sodium
 Nerve function
 Muscle contraction
 Chloride
 HCl production
 Removal of carbon dioxide
 Immune function
Sodium & Chloride Deficiencies
 Infants & children
 Diarrhea and vomiting
 Athletes
 Endurance sports
 Symptoms
 Nausea, dizziness, muscle cramps, coma
Overconsumption of Sodium
Chloride
 Increased blood pressure
 Susceptible individuals
 Elderly
 African Americans
 Those with:
 Hypertension
 Diabetes
 Chronic kidney disease
Focus on Food – Salt: Is It Really
So Bad?
 Salt sensitivity affected by:

 Genetics
 Exercise
 Responsiveness of renin-angiotensin-
aldosterone system
Chlorine
 Functions
 Acid-base and osmotic regulation
 HCl and chloride salts in gastric secretions
 Deficiencies
 Metabolic alkalosis
 Increased bicarbonate compensates for
decreased Cl
 Growth retardation
Sulfur
 Component of amino acids
 cystine, cysteine, and methionine for
bioactive and structural proteins
 wool contains about 4% sulfur
 Chondroitin sulfate is a constituent of
cartilage
 Deficiency is related to protein
deficiency
Magnesium
 Functions
 Associated with Ca and P
 70% of Mg in skeleton
 Enzyme activation (e.g., pyruvate dehydrogenase)
 Deficiency
 Hypomagnesemic tetany (grass tetany)
 early lactating cows on grass
 poor nervous and muscular control
Magnesium (Mg): Dietary
Sources & Bioavailability
 Green leafy vegetables, seafood,
legumes, nuts, dairy products,
chocolate, brown rice, whole grains

 Bioavailability influenced by:

 Calcium
 Phosphorus
Metabolism & Regulation of
Magnesium in the Body
 Stabilizes enzymes
 Neutralizes negatively charged ions
 Energy metabolism
 Cofactor for over 300 enzymes
 DNA & RNA metabolism
 Nerve & muscle function
Magnesium Deficiency & Toxicity
 Deficiencies
 Alcoholics
 Abnormal nerve & muscle function
 ? increase risk for CVD & type 2 diabetes
 Toxicity
 Large dose supplements
 Intestinal distress, alterations in heart beat
Potassium
 Functions
 Regulation of osmotic and acid-base balance
 Major cation of intracellular fluid
 nerve and muscle excitability
 Cofactor for several reactions in carbohydrate
metabolism
 Major salt in ruminant sweat
 Increases requirement in heat stress
 Typically high in forages
 Potassium (K): Dietary Sources &
Bioavailability
 Legumes, potatoes,
seafood, dairy
products, meat,
fruits/veg

 Bioavailability
 High
Regulation & Functions of
Potassium in the Body
 Absorption in small intestine & colon
 Blood potassium regulated by:
 Kidneys
 Aldosterone increases excretion
 Electrolyte
 Maintains fluid balance
 Muscle function
 Nerve function
 Energy metabolism
Potassium Deficiency & Toxicity
 Deficiency
 Diarrhea & vomiting
 Diuretics
 Hypokalemia
 Symptoms
 Muscle weakness, constipation, irritability,
confusion, ? insulin resistance, irregular heart
function, decreased blood pressure, difficulty
breathing
 Toxicity
 Supplementation
The Trace Minerals: An Overview
 Inorganic atoms or molecules

 Microminerals or trace elements

 < 100 mg/day needed

Bioavailability & Regulation of
Trace Minerals
 Bioavailability influenced by:
 Genetics
 Nutritional status
 Nutrient interactions
 Aging
 Absorbed in small intestine
 Circulated in blood
 Deficiencies & toxicities rare
 Except genetic disorders & environmental
exposure
 Functions of Trace Minerals in the
Body
 Cofactors
 Metalloenzyme
 Components of nonenzymatic molecules
 Provide structure to mineralized tissues
Trace Elements (minerals)
 Need small amounts of these.
 Found in plants and animals.
 Content in plant foods depends on soil
content (where plant was grown).
 They are difficult to quantify biochemically.
 Bioavailability often influenced by other
dietary factors (especially other minerals)
 Iron
 Most common nutrient
deficiency in the world.
 Functions
 Oxygen transport via hemoglobin
 Thus, necessary for ATP
production!
 Essential component of many
enzymes
 Immune function
 Brain function
 Iron deficiency/toxicity thought to
slow mental development in kids.
Iron in the Body
 70% of iron in body is functional; found
in enzymes and other molecules
 >80% of this found in red blood cells
 30% of iron is in storage depots or
transport proteins
 Iron absorption, transport, storage and
loss is highly regulated.
Iron Absorption
 Primary regulator of
iron homeostasis
 1-50% of iron is
absorbed.
 If body needs more
iron, it increases
amount of “transferrin”
an iron carrying protein.
 Iron can also be stored
in another protein called
“ferritin”
Iron Absorption
 Transport across
 Brush border
 Basolateral membrane
 Heme iron
 Chemical modification not needed
 Nonheme iron
 Reduced to ferrous form
 Ferritin
Effect of Iron Status on Iron
Absorption
Effect of Iron Status on Iron
Absorption
 Iron deficiency
 Increases production of transport proteins
 Decreases ferritin production
 Adequate or excess iron
 Decreases production of transport proteins
 Iron Circulation, Uptake Into
Cells, & Storage
 Transferrin
 Delivers iron to body
cells
 Transferrin receptors
Iron Circulation, Uptake Into
Cells, & Storage
 Iron storage compounds

 Ferritin
 Main storage form
 Hemosiderin
 Long-term storage
 Absorption, cont.
 Iron from animal sources
much better absorbed than
that from plant sources
 Absorption of iron from
plant sources increased by
 Vitamin C
 Meat in diet
 Absorption is decreased by
 Phytates (grain products)
 Polyphenols (tea, coffee)
 Other minerals (calcium, zinc)
Iron Deficiency Anemia
 Public health concern in U.S. and around the
world.
 Infants, children, pregnant and lactating
women most at risk.
 Symptoms
  hemoglobin concentration of blood
  red blood cell size
 Cognitive problems, poor growth, decreased
exercise tolerance.
Iron (Fe): Dietary Sources
 Heme iron
 Bound to a heme group
 Shellfish, beef, poultry, organ meats
 Makes up
 Hemoglobin, myoglobin, cytochromes

 Nonheme iron
 Green leafy vegetables, mushrooms, legumes,
enriched grains
 ~85% of dietary iron
Bioavailability of Iron
Influenced by:
 Form

 Heme
 Ferric
 Ferrous
 Iron status
 Presence/absence of other dietary
components
Enhancers of Nonheme Iron
Bioavailability
 Vitamin C & stomach acid
 Convert ferric to ferrous iron

 Meat factor
 Compound in meat, poultry, seafood
 Meat + nonheme iron
Inhibitors of Nonheme Iron
Bioavailability
 Chelators

 Phytates
 In vegetables, grains, seeds
 Polyphenols
 Some vegetables, tea, coffee, red wine
Functions of Iron
 Oxygen transport: hemoglobin

 Iron reservoir: myoglobin

 Cellular energy metabolism

Oxygen Transport: Hemoglobin
 Most abundant
protein in red blood
cells
 4 protein subunits +
4 iron-containing
heme groups
 Delivers oxygen to
cells
 Picks up carbon
dioxide
Iron Reservoir: Myoglobin
 Found in muscle cells
 Heme group + protein subunit
 Releases oxygen to cells when needed
for:
 ATP production
 Muscle contraction
Cellular Energy Metabolism
 Cytochromes
 Heme-containing complexes
 Function in electron transport chain
 Allow conversion of ADP to ATP
 Iron as cofactor
 Electron transport chain
 Citric acid cycle
 Gluconeogensis
Other Roles of Iron
 Cytochrome P450 enzymes

 Cofactor for antioxidant enzymes

 Protects DNA, cell membranes, proteins

 Cofactor for enzyme to make DNA

Iron Deficiency
 Most common nutritional deficiency

 At-risk groups
 Infants, growing children, pregnant women

 Pica
Mild Iron Deficiency
 Signs
 Fatigue
 Impaired physical work performance
 Behavioral abnormalities
 Impaired intellectual abilities in children
 Body temperature regulation
 Influences immune system
Severe Iron Deficiency: Iron-
Deficiency Anemia
 Microcytic hypochromic anemia
 Small, pale red blood cells
 Inability to produce enough heme
 Decreased ability to carry oxygen
 Decreased ATP synthesis
Focus on Clinical Applications:
Measuring Iron Status
 Serum ferritin concentration
 < 12 micrograms/L
 Total iron-binding capacity
 > 400 micrograms/dL
 Serum transferrin saturation
 < 16%
 Hemoglobin concentration
 Men < 130 g/L Women < 120 g/L
 Hematocrit
 Men < 39% Women <36%
Basics of Iron Supplementation
 Ferrous Iron
 Best absorbed
 Other terms:
 Ferrous fumarte
 Ferrous sulfate
 Ferrous gluconate

 Ferric Iron
Iron Toxicity
 Medicinal or supplemental iron
 Most common cause of childhood
poisoning
 Symptoms
 Vomiting, diarrhea, constipation, black
stools
 Death
 Excess deposited in liver, heart,
muscles
Special Recommendations for Vegetarians
& Endurance Athletes
 Vegans
 Needs are 80% higher
 Iron supplements
 Heme + nonheme iron foods
 Endurance athletes
 Increased blood loss in feces/urine
 Chronic rupture of red blood cells in feet
 Needs are 70% higher
Copper (Cu): Dietary Sources &
Bioavailability
 Forms
 Cupric
 Cuprous
 Organ meats, shellfish, whole-grain
products, mushrooms, nuts, legumes
 Bioavailability decreases with
 Antacids
 Iron
Absorption, Metabolism, &
Regulation of Copper
 Absorbed in small intestine & stomach
 Influenced by Cu status
 Ceruloplasmin
 Excess incorporated into bile &
eliminated in feces
Functions of Copper
 Cofactor for metalloenzymes in redox
reactions:
 ATP production
 Cytochrome c oxidase
 Iron metabolism
 Neural function
 Antioxidant function
 Superoxide dismutase
 Connective tissue synthesis
Copper Deficiency & Toxicity
 Deficiency
 Hospitalized patients & preterm infants
 Antacids
 Signs & Symptoms
 Defective connective tissue, anemia, neural
problems
 Toxicity
 Rare
Copper
 Functions
 Essential for normal absorption, transport
and mobilization of iron and hemoglobin
synthesis
 Integral component of many enzymes
(e.g., cytochrome oxidase)
 Stored in most tissues, especially liver
Copper Deficiency
 Anemia
 Depigmentation of hair or wool
 Black sheep are sometimes kept as
indicators of marginal Cu deficiency
 Loss of wool crimp (“steely” wool)
 Bone disorders
 Central nervous lesions with muscular
incoordination
Induced Copper Deficiency
 Caused by relatively high levels of Mo
and/or S
 Site of interaction is in the rumen
 Formation of insoluble Cu salts including
sulfides and thiomolybdates
 Net effect is decreased Cu absorption
Induced Copper Toxicity
 Occurs with “normal” dietary levels of
Cu and “low” levels of Mo and S
 Accumulates in liver
 Sheep are more susceptible than cattle
or pigs
Iodine
 Function
 Essential component of
thyroid hormones
 Important for regulation
of body temperature,
basal metabolic rate,
reproduction and
growth.
 Regulation in body
 Almost all is absorbed.
 Excess removed in urine.
Dietary Sources
 Seafoods
 Milk/dairy products
 Iodized salt
Iodine Deficiency
 Goiter (less severe)
 Enlarged thyroid gland due to body’s
attempt to increase thyroid hormone
production
 Cretinism (more severe)
 Severe iodine deficiency during
pregnancyserious problems in baby
 Stunted growth, deaf, mute, mentally retarded.
 Iodine Deficiency Disorders
 Cretinism  Goiter
Absorption, Metabolism, &
Regulation of Iodine
 Absorbed in small intestine & stomach
 Taken up by thyroid gland
 Thyroid-stimulating hormone regulates
uptake
Functions of Iodine
 Component of:
 Thyroxine (T4)
 Triiodothyronine (T3)
 Regulates energy metabolism, growth,
development
 Signs of deficiency
 Severe fatigue
 Lethargy
Focus on Food: Iodine Deficiency &
Iodine Fortification of Salt

 1920s – “Goiter Belt”

 Statewide campaigns
 Started providing iodized salt to children
 Goiter almost eliminated
 Current – Public Health working to
eradicate goiter internationally
Iodine Toxicity
 Hypothyroidism
 Hyperthyroidism
 Formation of goiters
Absorption, Metabolism, &
Regulation of Selenium
 Most Se enters blood
 Incorporated into selenomethionine
 Makes selenoproteins
 Stored in muscles
 Maintenance of Se through excretion in
urine
Functions of Selenium
 Component of glutathione peroxidase
 catalyzes removal of hydrogen peroxide

GSH + H2O2 GSSG + H2O

GSH = reduced glutathione
GSSG = oxidized glutathione
 Component of iodothyronine-5’- deiodinase
 Converts T4 to T3
 Improves killing ability of neutrophils
 Reduces the prevalence and severity of mastitis
Selenium
 Protects cells from autooxidative
damage
 Shares this role with vitamin E
 Important antioxidant
 Deficiencies
 White muscle disease in lambs and calves
 Skeletal and cardiac myopathies
 Exudative diathesis (hemorrhagic disease)
in chicks
Selenium Content of Soils
Selenium
 Toxicity
 Blind staggers or alkali disease
 Range between minimum requirement and
maximum tolerable level is narrow
 Supplementation must be done with care!
 FDA regulations allow two forms of inorganic
Se (Na selenite and Na selenate) to be used
 0.3 mg of supplemental Se/kg of DM is maximum
 Organic form available
Selenium Deficiency & Toxicity
 Deficiency
 Keshan disease
 Toxicity
 Garlic-like odor of breath
 Nausea
 Vomiting
 Diarrhea
 Brittleness of teeth & fingernails
Chromium (Cr): Dietary Sources,
Bioavailability, & Regulation
 Food content depends on soil
 Whole grains, fruits/veg, processed
meats, beer, wine
 Bioavailability affected by:
 Vitamin C
 Acidic medications
 Antacids
 Transported in blood to liver
 Excess excreted in urine & feces
Functions of Chromium
 Regulates insulin
 Growth & development
 Lab animals
 Increases lean mass
 Decreases fat mass
 Ergogenic aid
 Chromium picolinate
Chromium Deficiency & Toxicity
 Deficiency
 Hospitalized patients
 Elevated blood glucose
 Decreased insulin sensitivity
 Weight loss
 Toxicity
 Rare
 Industrially released chromium
Manganese (Mn): Dietary Sources &
Regulation

 Whole grains, pineapples, nuts,

legumes, dark green leafy vegetables,
water
 <10% absorbed
 Excess incorporated into bile & excreted
in feces
Functions of Manganese
 Cofactor for metalloenzymes
 Gluconeogenesis
 Bone formation

 Energy metabolism

 Cofactor for superoxide dismutase

Manganese Deficiency & Toxicity
 Deficiency
 Rare
 Scaly skin, poor bone formation, growth
faltering
 Toxicity
 Rare
 Mining
 Liver disease
 High water levels
Molybdenum (Mo): Dietary
Sources
 Food content depends on soil
 Legumes, grains, nuts
 Absorbed in intestine
 Circulated to liver via blood
Functions of Molybdenum
 Redox reactions

 Cofactor for several enzymes

 Metabolism of:
 Sulfur-containing amino acids
 DNA & RNA

 Detoxifying drugs in liver

Molybdenum Deficiency & Toxicity
 Deficiency
 Rare
 Toxicity
 No known effects in humans
 Animals – disrupts reproduction
Zinc (Zn): Dietary Sources &
Bioavailability
 Bioavailability influenced by:
 Phytates
 Iron
 Calcium
 Animal sources
 Acidic substances
Absorption, Metabolism, &
Regulation of Zinc
 Requires proteins to:
 Transport zinc into enterocyte
 Metallothionine
 Bind zinc within cell
 Excess excreted in feces
 Genetic influences
 Acrodermatitis Enteroathica
 Zinc deficiency even
with adequate
amounts of dietary
zinc
 Supplementation
 Infants
 Growth failure
 Red/scaly skin
 Diarrhea
 Human Genome
Project
Functions of Zinc
 Cofactor
 RNA synthesis
 Stabilizes proteins
that regulate gene
expression
 Zinc fingers
 Antioxidant
 Stabilizes cell
membranes
Zinc Deficiency & Toxicity
 Deficiency  Toxicity
 Decreases appetite
 Increases morbidity
 Decreases growth
 Skin irritations,
diarrhea, delayed
sexual maturation
 Supplements
 Poor immune
function
 Depressed levels of
HDL
 Impaired copper
status
 Nausea, vomiting,
loss of appetite
Fluoride
 99% is found in
bones and teeth
 Function
 to promote
mineralization of
calcium and
phosphate.
 Inhibits bacterial
growth in
mouthdecreases
cavity formation.
Fluoride (F-): Dietary Sources,
Bioavailability, & Regulation
 Not an essential nutrient
 Potatoes, tea, legumes, fish w/bones,
toothpaste, added to drinking water
 American Dental Association
 Fluoridation 1-2 ppm
 Absorbed via small intestine
 Circulates in blood to liver & then teeth &
bone
 Excess excreted in urine
Functions of Fluoride
 Part of bone & teeth matrix
 Stimulates maturation of osteoblasts
 Topical application decreases bacteria in
mouth
 Fewer cavities
Fluoride Deficiency & Toxicity
 Deficiency
 None known
 Toxicity
 GI upset, excessive production of saliva,
watery eyes, heart problems, coma
 Dental fluorosis
 Skeletal fluorosis
Cobalt
 Known since 1930s
that a wasting
disease was
associated with Co
deficiency in plants
and soils
 Starved for glucose!
 Vitamin B12 was
found to contain Co
Vitamin B12
Cobalt Deficient Areas of the US
Cobalt and Vitamin B12
 Injection of Co-deficient sheep and
cattle with Vitamin B12 was as effective
as feeding Co in curing the disease
 Injection of Co had no effect
 Microbial synthesis of Vitamin B12 was
the key!
Functions of Cobalt and Vitamin B12
 Essential coenzyme for
 Propionate metabolism
 methylmalonyl CoA to succinyl CoA
 DNA synthesis
 Bacterial synthesis of methionine
Other Trace Minerals
More research needed about:
 Nickel

 Aluminum

 Silicon

 Vanadium

 Arsenic

 Boron
 Referens
 Harper’s Ilustrated Biochemistry 27th ed.
(Robert K Murray, Daryl K. Granner, Victor W.
Rodwell, 2006)
 Medical Biochemistry (John Baynes, Marek H
Dominiczak, 2005)
 Color Atlas of Biochemistry (Koolman, 2005)
 The Medical Biochemistry Page
(www.themedicalbiochemistrypage.org)
 Konsultasi kuliah: Bagian Biokimia FK UNHAS
atau syahrijuitakadir @yahoo.com