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Minerals ,trace elements
and vitamins
Karel Kotaska
Minerals
1. Macronutrients
building of the systems (water, proteins, fats, sacharides, lipids)
C, H, O, N, S
2. Dietary important minerals (More than 100 mg /day)
Ca, P, Mg, Na, K, Cl
3. Trace elements
Cr, Co, Cu, Fe, Mn, Mo, Zn, Se, I, F
4. Added elements (not essential for human)
Ni, Si, Sn, V, B, Li
5. Toxic ELEMENTS
Pb, Hg, Cd
Minerals
TRACE ELEMENTS AND
MINERALS
• Transport mechanisms of trace elements
–
–
–
–
–
albumin - Cu, Zn
transferin - Fe, Cr, Mn, Zn
aminoacids - Cu, (Fe in small amount)
transcobalamin - Co
globulins - Mn
TRACE ELEMENTS AND
MINERALS
• Elimination of minerals and trace elements
–
–
–
–
–
Bile – Cr, Cu, Mn, Zn
Urine – Co, Cr, Mo, Zn
pancreatic juice - Zn
sweat - Zn
mucotic tissue – Fe, Zn
Trace elements
Main biological functions
- catalysers of various chemical reaction, parts of
metalloproteins
- modulation of enyzmatic activities in inermedial
metabolism of aminoacids, lipids and sacharides
- Structural function in various cell components (nuclear
proteins, DNA, membranes)
Trace elements - RDA
RDA per os (men)
Zn
Fe
Cu
Se
Mn
Cr
Mo
J
F
Parenteral RDA
USA
UK
EU
11
9,5
9,5
3,2 - 6,5
168
145
145
50 - 100
8
8,7
9,0
1,2
µmol
143
155
161
20
mg
0,9
1,2
1,1
0,3 - 1,3
µmol
14
19
17
5 - 20
µg
55
75
55
30 - 60
µmol
0,7
1,0
0,7
0,4 - 0,8
mg
2,3
1,4
1-10
0,2 - 0,3
µmol
42
25
18-182
3-5
µg
35
> 25
10 - 20
1-4
> 0,5
0,2 - 0,4
µg
45
50 - 400
19
µmol
0,5
0,5 - 4,2
0,2
µg
150
140
130
131
µmol
1,2
1,1
1,0
1
mg
4,0
0,05/kg (children)
0 - 0,95
µmol
210
2,6/kg (children)
0 - 50
mg
µmol
mg
µmol
Preanalytical aspects of trace
elements investigation
Sample storage and collection
Blood
-Avoid contamimation
-Commonly used syringes can contamine sample with Fe, Mn, Ni, Cr and K
- Special collecting systeme with silicone coated syringes
- Zinc contamination if rubber cups are used
- Zn is about 5 to 15 % elevated in serum - is released from erythrocytes during
clotting
-hemolysis, elevation of Fe, Zn and Mn
Preanalytical aspects of trace
elements assays
Urine
- collection into polyethylene (PE) tubes (including PE caps)
- tubes are before use added 24 h in 10% nitric acid, immediately before
use tubes are washed by deionised water
Hair
- hair are collected from the top of the head (0,5 g) into PE bags or paper
envelopes
- Before assays are hair are washed according to the WHO guidelines
(acetone, water 3x, acetone).
Preanalytical aspects of trace
elements assays
Sample storage
- Urine, blood 3 days in 4C, 1 year at -20C,
- hair, nails after drying in closed PE tubes at room temperature
- Stabilization of samples by using HCl or HNO3 absolute (1% v/v) in some assays
Sample contamination
- is inevitable to use superclean reagents and water
Most important analytical
procedures for investigattion of
trace elements
●
●
●
●
●
●
●
●
●
●
●
●
Atomic absorption spectrometry with electrotermic atomization (ETA-AAS)
Flame atomic absorption spectrometry (FAAS)
AAS
ICP-AES
P-AFS
ICP-MS
NAA
XRFS
Voltammetry
Polarography
Immunochemistry
ISE
Copper
Copper
Copper
• Absorption in gut – metallothionein (Cu2+ is
insoluble). Intracelular protein involved in Cu
metabolism (distribution and cellular utilization of Cu).
• Ceruloplasmin (CP) - glycoprotein, Cu-dependent
feroxidase
– bond 6 – 7 Cu atoms
– 80 - 95% total plasma Cu ,
– oxidation of Fe2+ to Fe3+ during iron absorption in GIT
Copper
Wilson disease – autosomal recesive disease – Cu is not bind to
apoceruloplasmin
• Low serum or plasma Cu
• Loss of Cu - liver impairment, mental retardation
• Ceruloplasmin where Cu is missed does not acts as feroxidase.
Menkes disease – X-linked disease –impaired Cu absorption in intestine.
Signs:
– decreased Cu absorption,
– increased concentration of Cu in urine and abnormal cellular transporttwisted of the hair, arterial wall defect, delayed development, spasms
Childhood, early death (3 years of age)
Copper
Iron
Iron metabolism
Iron
Hemochromatosis – genetic disease
• Increased Fe absorption (2 – 3 mg/day instead of 1 mg)
increased Fe accumulation in tissues
• Middle aged men, in women signs occur 10 -15 years later
Symptoms
Liver cirrhosis, hepatomegaly, DM 2. type, arthropaties, bronze
skin
Iron
Hemosiderosis
• Hemosiderin - micelar form of Fe after feritine degradation
• Thalasemia and erythrocyte impairment
• Prolonged alveolar bleeding - Fe is accumulated in macrophages
• Lung fibrosis
Iron
Reference values
0 - 6 weeks
6 weeks - 1 year
1 - 15 years
11,0 - 36,0 µmol/l
6,0 - 28,0 µmol/l
4,0 - 24,0 µmol/l
males
15 - 60 years
90 - 150 years
7,2 - 29,0 µmol/l
7,0 - 23,0 µmol/l
Females
15 - 60 years
90 - 150 years
9,0 - 28,0 µmol/l
6,0 - 24,0 µmol/l
Molybdene
Important for various metalloenzymes :
– xantinoxidases
– aldehydoxidases
– sulfitoxidases
Molybden cofactor
• Dietary molybden intake interferes with Cu – less
utilization of CU in organism).
Manganese
• Increased concentration in mitochondria
• Activation of glycosyltransferases
• Inevitable for superoxiddismutases
and also other enzymes :
–
–
–
–
hydrolases
kinases
dekarboxylases
transferases
Mn deficiency increases concentration of glycoproteins and
proteoglycans
Zinc
Zinc
Zinc
• Important for nucleic acid synthesis
• Zn/Cu-superoxiddismutase – antioxidation processess
• Immunity – T lymfphocytes differentiation
• Correct gonadal function
•
Deficiency – decreased intake – systemic disorders
Zinc
• Acrodermatitis enterohpeatica
Reference values:
0 - 6 weeks
6 weeks - 60 years
60 - 90 years
90 - 150 years
9,1 - 13,7 µmol/l
9 - 16 µmol/l
9,6 - 16,4 µmol/l
8 - 15,1 µmol/l
Zinc
Reference values in various biological materials
Cobalt
• Part of cobalamine – vitamin B12 (pyrrolic
core).
•
Absorption in gut and incorporated in B12
Selenium
• Important part of glutathionperoxidase
– protection against peroxidation, oxidative stress, UV light, important for
metabolism of xenobiotics
Selenium
• Thyronine deiodinase - metabolic regulation of
thyroid hormones
3 types of deiodinase
Type I – 5´ deiodination
Type II - T4 toT3 deiodination
Type III – deiodination of T4 toT3 and T3 to T2
Selenium
• Translation tRNA – proteins
- lenghthening of polypeptide chain
Selenium
Importance of Se in immune systeme
– Lack of Se decrease T-lymfocytes function
– Decrease ability of antibody formation
Se poisoning – hemolytic anemia, degenerative changes in
parenchyme, hemosiderosis
Selenium
Reference values
6 months - 1 year
1 - 15 years
15 - 60 years
18 - 101 µg/l
58 - 121 µg/l
74 - 170 µg/l
Chromium

Regulation of glucose and lipid metabolism
Glucose factor (GTF) – control of glycemia, complex of Cr with
nicotinic acid and Gly,Glu, Cys
- binding of glucose to receptors
Fluoride
•Anorganic matrix teets and bones
•Lack - osteoporosis, karies
Iodine


thyreoid hormons
Lack of iodine - goiter
Borone
 utilization of Ca, Cu, Mn, N, glucose and triacylglycerols
 stabilization of biomembranes
 – inhibition of energetic metabolism and immune system
burning)
(respiration
Vitamins
Vitamins
RDA -vitamins
Vitamin
Males
Females
A
Retinol (mg)
1,00
0,80
pregnancy (after 4. month)
1,10
Elderly
1,50
Parenteral intake/24 hrs
1,00
B1
Thiamin (mg)
< 50 years
1,5
1,1
> 50 years
1,2
1,1
Parenteral intake/24 hrs
100 µg/100 kcal of diet
B2
Riboflavin (mg)
< 50 years
1,7
1,3
> 50 years
1,3
1,1
Parenteral intake/24 hrs
3,6
RDA -vitamins
Vitamin
Males
Females
B3
Niacin (mg)
< 50 years
19
16
> 50 years
15
14
Parenteral intake/24 hrs
40
B6
Pyridoxin (mg)
0,016 - 0,020 mg of B6/g of protein
< 50 let
2,0
1,6
> 50 let
1,7
1,7
Parenteral intake/24 hrs
4,0
B7
Biotin (µg)
< 50 let
30 - 100
> 50 let
30
Parenteral intake/24 hrs
60
RDA -vitamins
Vitamin
Males
Females
B12
CN-kobalamin (µg)
< 50 years
2,0
> 50 years
2,4
Parenteral intake/24 hrs
5,0
vitamin C (mg)
< 50 years
100
60
> 50 years
90
75
Parenteral intake/24 hrs
100
D
vitamin D3 (mg)
< 50 years
0,005
0,005
> 50 years
0,015
0,010
Pregnancy
Parenteral intake/24 hrs
0,005
0,005
RDA -vitamins
Vitamin
Males
Females
E
Tocopherols (mg)
< 50 years
10
8 - 10
> 50 years
15
15
pregnancy
13
Parenteral intake/24 hrs
10
K
vitamin K1 (mg)
< 50 years
0,080
0,065
> 50 years
0,060
0,060
Pregnancy
Parenteral intake/24 hrs
0,060
0,150
RDA -vitamins
Vitamin
Males
Females
Carotenoids
beta-carotene (mg)
1,6
Folic acid (mg)
< 50 years
0,20
0,18
> 50 years
0,40
0,40
pregnancy
Parenteral intake/24 hrs
0,60
0,40
Pantothenic acid (mg)
< 50 years
4–7
> 50 years
5
Parenteral intake/24 hrs
15
Reference values
Males
Females
Vitamin
A
Retinol
Serum - adults
1,05 – 2,27 µmol/l
0,83 – 1,75 µmol/l
Serum - newborns
1,22 – 2,60 µmol/l
Serum - choldren
1,05 – 2,80 µmol/l
B1
Thiamin
Serum
< 0,075 µmol/l
B2
Riboflavin
Whole blood
0,361 – 1,770 µmol/l
serum
0,133 – 0,478 µmol/l
B3
Niacin
Serum
2 – 12 mol/l
Whole blood
16 – 73 mol/l
Reference values
Males
Females
Vitamin
B6
Pyridoxin
Serum
0,106 - 0,638 µmol/l
Plazma
> 0,243 µmol/l
Erytrocytes
0,266 -1,330 µmol/l
Urine
> 0,320 µmol/l/d
B7
Biotin
Serum/plazma
0,15 - 0,37 µmol/l
Urine
0,03 - 0,25 µmol/l
B12
CN-kobalamin
Serum - newborns
0,118 – 0,959 nmol/l
Serum - adults
0,162 – 0,694 nmol/l
Serum - pregnancy
< 0,125 nmol/l
vitamin C
Plazma
Leukocytes
34 - 114 µmo/l
8
20 – 53 µg/10 leukocytes (1,14 – 3,00 fmol/leukocyte)
Reference values
Males
Females
Vitamin
D
vitamin D3
Serum - children: 1,25 (OH)2
0,075 – 0,175 nmol/l
Serum - adults: 1,25 (OH)2
0,050 – 0,200 nmol/l
Serum - summer - adults: 25–OH
50 – 300 nmol/l
Serum - winter - adults: 25–OH
25 – 125 nmol/l
Serum - summer – healthy (95% CI): 25–OH
41,6 - 192,4 nmol/l
E
Tocoferol
Serum - 0 – 1 month
8 – 28 µmol/l
Serum - 1 – 6 months
10 – 31 µmol/l
Serum - 6 months – 6 years
20 – 30 µmol/l
Serum - adults
19 - 35 µmol/l
Reference values
Males
Females
Vitamin
K
vitamin K1
Serum
0,3 – 2,64 nmo/l
Carotenoids
beta-carotene
serum: beta-carotene
0,93 - 3,72 µmol/l
Folic acid
Serum - adults
> 0,0135 µmol/l
Erythrocytes - adults
> 0,360 µmol/l
Serum - newborns
0,016 – 0,072 µmol/l
Panthotenic acid
Serum
4,7 – 8,4 µmol/l
Vitamin A and carotenoids
retinol, all-trans-3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)2,4,6,8-nonatetraen-1-ol
C20H30O
Mh: 286,4
Sources – liver, milk products and fat fishes,
yolk, yellow and orange vegatable, dried
apricots, leafy vegetable
- in plazma bind to retinol binding protein
(RBP).
-Carotenoids are bind coupled with LDL, HDL
and lipoproteins
- 80-90 % stored in liver
-beta-carotene is converted to vitamin A by
enzymatic oxidation
(A) all-trans retinol, (B) all-trans retinaldehyde,
(C) all-trans retinoic acid, (D) retinylphosphate
Vitamin A and carotenoids
Vitamin A and carotenoids
Vitamin A and carotenoids
Functions
●
retinal fotoreception
●
epitelial dysfunction
●
lipoprotein and subcellurar integrity
●
lysosomal stability
●
Act on the steroid and glykoprotein syntehsis
●
Main component of reproductions and embryogenesis
●
Tissue proliferation and diferetiation
●
Imunological integrity
●
Gene expression, cancerogenesis
●
Bone growth
●
antioxidants
Target organs
- Liver tissue (fyziological storages for 2 years).
- capacity is decreased in liver diseases, zinc defficiency (inevitable for Zn mobilization)
and alcoholism.
Vitamin A and carotenoids
Resorption
- in duodenum relevant to amount of fats, proteins, bile acids and pancreatic lipase
- Esters dissolved in fats and emulgated in bile are hydrolyzed in intestine to retinol and
are absorbetd to intestinal epitelia where retinal is formed
- Incorporated into LDL and HDL and stored in liver adipocytes.
Deficiency symptomes
- gloomy, xerophtalmia tongue inflammation, folicular hyperkeratosis or ichtyosis,
Keratinization of epitelial cells in respiratory, gastrointestinal and genitourenal tract
xerodermia, karies, lack of appetite.
Impaired immunity (low activity of T lymphocytes)
Vitamin A and carotenoids
Toxicity
Doses above 20x normal values for children and more 100x for adults.
Signs of toxicity
- Alopecia, anemia, head aches, dermatitis, diplopia, hepatomegalia, hypercalcemia,
hyperlipidemia, irregular menstruation, insomnia, patological births, bone disorders,
liver dysfunction, spontaneous abortions, vomitting.
Elevated levels
Diabetes mellitus, hepatomegaly, idiopathic hypercalcemia in children,
hypercholesterolemia, hyperlipidemia, hypervitaminosis A, vitamin A intoxication,
chronic renal diseases, pregnancy.
Decreased values
cystic fibrosis, hepatitis, hypothyreosis, kwashiorkor, malabsorption, malnutrition,
nefritis, fat absorption diseases, growth impairment, sprue, carcinoid, gloomy,
xerophtalmia, tuberculosis.
Vitamin A and carotenoids
Interfering factors causing decreased values
Alcohol, drugs (allopurinol, cholestyramin, diethylstilbestrol, neomycin).
Biochemical interactions of vitamin A intake
In serum
In urine
2+
↑ ALP, bilirubin, Ca , glucose, prothrombin ↑ urine volume
time
↓ erythrocyte count, hemoglobin, hematocrit,
leucocyte count, parathyrine
Therapeutic dosing
●
●
●
Gloomy
Acne
Oncological diseases prevention and therapy (i. e. promyelocytic leukemia)
Vitamin D
vitamin D3 - cholecalciferol
Two equivalent forms
C27H44O
Mh: 384,6
CAS: 67-97-0
vitamin D2
vitamin D3
synonymum
ergocalciferol
cholecalciferol
precursor
ergosterol
7-dehydrocholesterol
synthesis
syntetic (UV)
Skin (UV)
ergokalciferol contains double bond between
C22-23 and additional methylic group on
side chain
Vitamin D
Vitamin D metabolism
Vitamin D
Vitamin D regulation
Sources
-Fishes (mackerel, tuna, herring),
yolk, liver, milk, butter
- Concentrations of vitamin D and
metabolites in serum oscillate
according to the season (UV light)
and dietary intake
Vitamin D
Other vitamin D regulation
Vitamin D3
(active)
Vitamin D2
(inactive)
Vitamin D
vitamin D3 and gut
-Stimulation of calcium excretion without relationship to PTH.
-Synthesis and phosphorylation of (CaBP) by proteinkinases and calcium
transport activation in enterocytes
vitamin D3 and bones
- Colagen matrix induction and proliferation
- if Ca level is decreased, then vit D3 stimulates bone rsorption and osteoclast
and mobilizes Ca without relationship to PTH
- Vit D deficiency in childhood and adult results in rachitis and osteomalatia
- Therapeutic dosing of vitamin D during parathyreoideal impairment could lead due to
decreased calcium reabsoprtion in kidney to elevated concentrations of calcium in urine
and high risk of nephrolitiases and nephrocalcinosis.
Vitamin D
Vitamin D3 and kidney
- increase of 24-hydroxylase activity.
- increase of syntesis less active 24,25(OH)2 vitamin D3 and loss of 1,25(OH)2
vitamin D3 production
-Stimulation of CaBP expression – increased Ca and P reabsorption in dist al and
proximal tubule
Vitamin D3 and parathyreoid glands
-1,25(OH)2 vitamin D3 decreases PTH synthesis
Vitamin D
Other functions of 1,25(OH)2 vitamin D3
- Control of proliferaton and diferentiation of normal and tumor cells
- Induction of production and maturation of IL-1
- Deficiency elevated the prevalence and severity of autoimmune diseases (multiple
sclerosis, arthritis, juvenile diabetes), increased risk of tuberculosis
- Inhibition of proliferation and stimulation fibroblast and kearatinocytes differentiation
- Importance in maturity and function of hair folicules
- Regulation of muscle contractility .
- Increased acumulation of Ca2+
- Important in reproductive function
- Neuroprotective efect
- Decreases calcitonin production, increase of insulin secretion and synthesis
- Activation of adenohypophyseal hormones
Vitamin D
Elevated 25-OH-D levels with s hypercalcemia - iatrogenic vitamin D intoxication
Decreased 25-OH-D levels
Depletion
cause (= indication to 25-OH-D investigation)
low offer
Low diet, UV light insufficiency
Impaired absorption
malabsorption
low hydroxylation
chronic hepatocelular lesion and cholestasis
Renal loss
Nephrotic syndroma complex
iatrogenic
anticonvulsives
loss of vit D-binding protein
Vitamin E (tocopherol)
alfa-tocopherol, 2,5,7,8-Tetramethyl-2-(4',8',12'-trimethyltridecyl)-6-chromanol
tocol
R1
R2
R3
Mh
Tocopherol
alpha
5,7,8-trimethyl
CH3
CH3
CH3
C29H50O2
430,7
beta
5,8-dimethyl
CH3
H
CH3
C28H48O2
416,7
gama
7,8-dimetyl
H
CH3
CH3
C28H48O2
416,7
delta
8-methyl
H
H
CH3
C27H46O2
402,7
-
tocol
H
H
H
-
-
Vitamin E
reabsorbed in small intestine (35 %), then s incorporated to
chylomicrons and transported to tissuues contains lipoporitein
lipases
-
- Stored in fats (in mitochondrial phospholipides, endoplasmic
reticulum and plasmatic membrane of erythrocytes and
respiratory tract cells)
- Excreted in liver (70 – 80 %) during 7 days, 20 – 30 % in
urine (tocoferic acid and gama lacturonides)
Vitamin E
Functions
●
Organism protection against the free oxygen radicals leading to vit A
oxidation and DNA damage
● Synergistic function with Selenium
● Mutagenic inhibition in GIT
● Membrane integritiy of neurological cells
● Erytrocyte protection against hemolysis
● Deficiency leads to increased concentration of lipoperoxidic substances
and to the cell membrane damage with cell death
● Therapeutic dosing before cardiovascular and reperfusion procedures
Vitamin E
Antioxidant functions
Vitamin E
Deficiency
●
●
●
●
anaemia, short life of erythrocytes
increased thrombocytal agregability
morphological changes of peripheral neurons
decreased of serum creatinine concetration with increase of renal creatinine
excretion
Prolonged deficiency
●
●
●
●
●
●
muscle myopathy and necrosis
inclusion in reticuloendothelial cells in bone marrow
Hypo- aand areflexia
Spinocereberal ataxia
Myopathy
Retinopathy
Vitamin E
Elevated serum vitamin E concentrations
- Hyperlipidemia, liver fibrosis, increased dietary vit E intake ,
pregnancy, renal failure
Decreased serum vitamin E concentrations
- Abetalipoproteinemia, hemolytic anemia, celrebellar ataxia, bile
tract atresia, coeliac disease, chronic cholestasis, liver cirrhosis,
enecefalomalatia, enteritis, gluten enteropathy, cystic fibrosis,
hemolysis, malabsorption, pancreatic tumors, peripheral
neuropathy, chronic pancreatitis, premature delivery, imbalances
in lipid resorption
Vitamin E
Interfering factors decreased serum vitamin E concentrations
● drugs (anticonvulsives, ethanol, phenobarbital, phenytoin, cholestyramin,
carbamazepine, clofibrate).
Biochemical interaction of vitamin E
- Urine
 aminolevulic acid, uroporphyrin
Sources
Sprouting corn (wheat) cotton oil , poppy, nuts, yolk
Toxicity
gastrointestinal problems, fatigue, headache, muscle weakness , coagulation
defects (together with Vitamin K deficiency).
Vitamin K
vitamin K1
C31H46O2
Mh: 450,7
vitamin K3 (menadione)
Esential cofactor acts in posttranslational
carboxylation of glutamic acid
-Important in coagulation factors (II, VII, IX a X )
and other important proteins (protein C, protein S
(Protein S free, Protein S total)
-Reaction is inhibited by anticoagulant substances
(warfarin)
For this reason is Vitamin K1 specific
antidotum of oral anticoagulants
(dicumarols).
vitamin K1 (phyloquinone)
Vitamin K
Vitamin K
-Resorption in intestine (10 – 80 %), bile, pancreatic enzymes and
correct fat absorption is necessary
- Absorption in lymph, late is transported to liver and other tissues. Liver
stored phylocinones (10 % ) and menachinones (90 %)
-Excretion – bile, urine
(60 - 70 % of phyloochinones is excreted in urine and faeces during
several days)
Symptoma of defficiency
Petecchia, bleeding
Vitamin K
Sources
- green leaves vegetable, vegatable oils.
- Menachinones are in ferrmented diets (cheese, yoghurts) and ruminant livers
Therapeutic indications
●
●
warfarine intoxication
anticonvulsives (phenobarbitalu, diphenylhydantoin) in pregnancy
Deficiences
●
●
●
●
lipid malabsorption
drug interaction
high doses of vitamin A and E
liver fibrosis
Signs of defficiency
●
bleeding (from petecchia to infaust hematemesis, melena, hematuria, hematoma)
Vitamin K
Prolonged deficiency
●
●
●
●
●
●
●
liver diseases
chronic pancreatitis
sprue
bile diseases, cholestasis
coeliac disease
inflammatory gut diseases
antibiotic therapy of gut infection
Possible reasons of decreased serum values
●
●
●
●
●
●
●
●
●
●
diarrhoea,
cystic fibrosis,
hypoprothrombinaemia,
chronic diseases treated by antibiotics
chronic lipid malabsorption
breast milk poor to vitamin K,
hemorhagic disease of newborns,
obstructive hepatitis,
gastrointestinal tract diseases
pancreatic diseases, liver, hemorrhagic diseases
Vitamin K
Interfering factors decreasing serum concentrations
 drugs – (vitaminu K antagonists, antibiotics, anticoagulants, cholestyramin,
hydantoins).
Vitamin K supplementation can affect various biochemical parameters:
in serum
In urine
 bilirubin (newborns),
 catecholamines
 proteins
17-hydroxycortikosteroids,
 erytrocytes
 porphyrins
Vitamin C
L-ascorbic acid, L-Threoascorbic acid, vitamin C
C6H8O6
Mh: 176,1
(A) Ascorbic acid,
(B) Dehydroascorbic acid
Source
Orange fruits and juices, strawberries, wild roses, parsley tops, black currant,
horsereadish, vegetables, potatoes.
Vitamin C
Storage in organism are to 35 – 40 days
Reference values
vitamin C in serum: 34 - 114 µmo/l
vitamin C in leukocytes: 20 – 53 µg/108 leukocytes (1,14 – 3,00 fmol/leukocyte)
Daily changes in serum is around 25 %, higher concentration – early morning, during
day slight decrease, maximal elevation – summer, minimal – winter,
in women – maximal elevation during ovulation
Low concentrations in serum
Alcoholism, anemia, febrilia, hemodialysis, hyperthyreoidism, smoking, malabsorption,
Tumors, obesity, acute and chronic inflammatory diseases, rheumatoid diseases, lead
Poisoning, high diet intake of Fe, scurvy, steatorhea, stress, pregnancy
Low concentrations in leukocytes:
Gastroduodenal diseases, post operations
Vitamin C
Elevated demand of vitamin C
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pregnancy, breast feeding (vitamin C is transported to breast milk)
surgical treatment, polytrauma, burns
tumors, x ray
parenteral diet
high vitamin E dosage
smoking
prolonged stress
chronic infection
prolonged expozition to cold
hyperthyreosis
hemodialysis
HIV
alcoholism
poisning
skin diseases
atherosclerosis
Vitamin C
Vitamin C in diet can effect several biochemical parametres
In serum
↑ oxalate
↓ TG
↓ uric acid
In urine
↑ glucose (false elevation)
↑ hemoglobin
↑ uric acid
crystals – cystin, oxalaty, urates
In faeces
↑ blood
Vitamin C
Drug interaction
 high vitamin C could decrease pH in urine and affect renal tubular reabsorption of
acid and basic drugs
 high doses intract with disulphiram –alcohol interaction
 Doses more than 10 g of vitamin C can decrease coumarin anticoagulants in GIT
Plasma concentration of vit C is decreased by acetylsalicylate, aminopyrine,
barbiturates,.p.o. kontracepties with estrogene.
Toxic effects
Extremely high doses (5 – 15 g/day) - sleeplessness, diarhoea, nausea, stomach
spasms, eczema
long time – osmotic diuresis
Vitamin B1 (Thiamin)
vitamin B1 x HCl, thiaminpyrophosphate (TPP) is cofactor
C12H17ON4S× HCl
Mh: 337,3
-Act in saccharide metabolism (glycolysis, pentosa-phosphate cycle, pyruvate – alpha
oxo glutarate change)
-Transketolase/transaldolase oxidative carboxylation affect periferal and central
nervous systeme functions and heart cells function
- Absorption in upper part of small intestine
Vitamin B1 (Thiamin)
Deficiency symptoms
Polyneuritis (beri-beri)
-Dried form of beri-beri –neurological impairment (peripheral nerves, sensoric and
motoric impairment in legs, parestezia, weaknesses)
-Wet form of beri-beri – dyspnoea, hepatomegaly, heart ailment, tachycardia,
generalized oedema, oliguria, ketone accumulation, lactate acidosis due to hypoxia,
metabolic acidosis
-Alcoholism - Wernicke encephalopathy (confusedness, ataxia, nystagm,
ophthalmoplegia)
Vitamin B1 (Thiamin)
Decreased serum levels
Alcoholism, megaloblastic anemia, beri-beri, dementia, diabetes mellitus, subacute
necrotic encephaloalopathy, prolonged hyperalimentation, lactation, dialysis, periferal
neuropathy, diarrhoea, feever, chronic liver diseases, impaired pyruvate oxidase
activity, heart ailment, hyperthyreosis, pregnancy,tumors, impaired dietary intake,
excessive tea drinking.
Interfering factors decreasing serum concentrations
Drugs (barbiturates).
Elevated serum levels
Hodgkin disease, leukemia polycythemia vera.
Sources
Yeast, bran, liver, rolled oats, rice, nuts, buckwheat, asparagus, black bread, wheat
sprouts, potatoes, beans.
Vitamin H (Biotine)
Biotin, vitamin B7
C10H16O3N2S
Mh: 244,3
Sources
yolk, liver, soya, chocolade,cauliflower, wheat, pea, yeast,
sea fishes.
Basic metabolic functions
-Carboxylation
- Carboxyl bond to N1 biotin is forming active intermediate
carboxybiotin-enzym (HCO3-, ATP, Mg2+ and acetyl-CoA).
Vitamin H (Biotin)
Function - carboxylation
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acetyl-CoA, propionyl-CoA, pyruvate,
fatty acid synthesis,
PUFA metabolism
propionic acid oxidation,
leucine oxidation
gluconeogenesis,
catabolism of branched aminoacides
cholesterol metabolism
cell growth
- decreased of muscle pain, ihibits hair greying and falling, improve nail quality, helps in
skin diseses
Vitamin H (Biotin)
Deficiency symptomes
rare
anorexia
nausea, vomiting
paleness
muscle pains
dried skin, hair falling
elevated cholesterol and bile acids
concentrations
● depression
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Important demand
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alcoholism
patients after gastrectomia
burns
pregnancy and breast-feeding
Low serum values
● inborn metabolic disorders
(-methylkrotonate, -hydroxyisovalerate,
-hydroxypropionate),
● prolonged parenteral diet
Pyridoxin (Vitamin B6)
Pyridoxin
pyridoxal, vitamin B6, pyridoxalphosphate (PLP)
C8H9O3N
Mh: 167,2
(A) pyridoxin, (B) pyridoxal, (C) pyridoxamine, (D) pyridoxic acid
Pyridoxin (Vitamin B6)
Active vitamin B6 forms and metabolites
Water soluble vitamin, syntetized in pllants and microorganisms, termal unstable
Pyridoxin (Vitamin B6)
Transport and metabolism
Pyridoxin (Vitamin B6)
Function
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enzymatic reactions
tryptophane conversion to nicotinic acid and sfingosin synthesis
glykogenphosphorylase activation in delta aminolevulic acid synthesis
DNA and heme synthesis
niacin synthesis (from tryptophan)
synthesis of neurotransmitters (serotonine, dopamine, noradrenaline, GABA)
taurine synthesis
myelin synthesis
hormone modulation effects
heme synthesis
immune functions
Pyridoxin (Vitamin B6)
Pyridoxin (Vitamin B6)
Sources
yeast, wheat sprouts, black bread, bananas, potatoes, nuts, sunflower seeds,
buckwheat,bran, harsh rye flower, meat (chocken, fish, liver), legumes
Deficiency symptoms
- sideroblastic anaemia,
- inborn apoenzyme abnormalities coupled with pyridoxal phosphate (newborn mental
retardations, skelet deformities, thrombosis, osteoporosis, aminoacidurias, vision
impairment)
- elevated homocysteine levels in adults
- eye corners and mind corner infections, folicular hyperkeratosis (= increased keratin
production and increased growth of skin cells around the hair pouches)
Pyridoxin (Vitamin B6)
Increased utility: hyperthyreosis, chronic infections
Indications to suplementation (doses up 300 mg during 6 months):
● vitamin B6 deficiency
● isoniazid therapy prophylaxion (10 – 20 mg/100 mg of isoniazide) to suppress
neurotoxicity
● homocystinuria, homocysteinemia
● sideroblastic anemia due to vitamin B6 deficiency
● adjuvant therapy of vomiting during gestation (50 – 80 mg/day).
● carpal tunnel syndroma
Decreased serum concentrations - chronic alkoholism, sideroblastic anemia, asthma
bronchiale, diabetes mellitus in gestation, dialysis, acute myocardial infarction, smoking,
lactation, leukemia, malabsorption and malnutrition, pelagra, preeklampsia,renal failure,
pregnancy, uremia
Pyridoxin (Vitamin B6)
Interfering factors decreased serum pyridoxine
concentrations:
Amiodarone, anticonvulsives, carbamazepine, cyclosporiny,
disulfiram, ethanol, hydralazine, isoniazide, L-dopa, oral
contraceptives, penicilamine, phenobarbital, phenytoin,
primidon, teophylin, tricyclická antidepressants
Excess
Sensoric neuropathy
Pantothenic acid
Coenzyme A (CoA), CoASH
- hydrolyzed in intestine and reabsorbed by gut
C9H16O5NNa
Mh: 241,2
- 70 % is eliminated in urine
- coenzyme A and esters
- essential in lipid and sacharide metabolism
Sources
-Animal products, grains, vegetables, syntetized in human intestinal mucosa
Pantothenic acid
Pantothenic acid
Function
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energy release from saccharides, lipides and ketonic aminoacids
heme and sterol synthesis
acetylation and gluconeogenesis
importance in lipid synthesis
Deficiency symptoms (rare)
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burning foot syndroma (impaired acetylation capacity)
hearing impairment
fatigue, and depression
sleep disorders
neurocirculation diseases
renal impairment
worsened wound healing
immune disorders, relevance to infections
Pantothenic acid
Therapeutic importance
● chromic malnutrition
● prolonged catabolism
● ethanol intoxication
Low serum levels occur in:
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mental anorexia,
immunodeficiency
sepsis
malabsorption syndroma
prolonged parenteral nutrition
Niacin (Vitamin B3)
Nicotinic acid, nicotinamide, vitamin B3, NAD+, NADP+, NADH, NADPH
C6H5O2N
Mh: 123,1
- absorbed from stomach and small
intestine
- oxidation metabolism, coenzymes,H+
transportation
- target tissues – muscles and liver
svalovina.
Sources
(A) nicotinic acid, (B) nicotinamide,
(C) nicotinamide adenine dinukleotide phosphate
- Meat (liver, tuna fish, poultry),
- Sunflower seeds, peanuts, black bread,
legumes, yeast
Niacin
Niacin cofactors
Functions
oxidation-reduction reaction
citrate cycle
saccharide metabolism
synthesis and oxidation of fatty acids
cellular metabolism
vasodilatation
NAD and NADPH coenzymes
hydrolyzed NAD takes part in DNA
replication
● total cholesterol to LDL transformation
● DNA reparation
● apoptosis
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Niacin
Niacin excretion
NAD synthesis
Niacin
Niacin defidciency
Pelagra - „three D disease": dermatitis, diarrhoea, dementia.
● gastrointestinal signs due to inflammation in vomititng and diarrhea
● pigment rash in UV light impact
● depresion, irritability, deyorientation, halucination, catatonia
Elevated niacine levels (overdosing):
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vasodilatation (headache, nausea, vomitting)
fulminant liver failure
severe forms of hepatitis
thrombocytopathia
myopathy
impaired sacharide tolerance during high dose treatment in diabetics
Niacin
Decreased serum levels
-alcoholism, liver cirrhosis, dietary defficiency of niacin, Hartnup disease, leucine
overdose, pelagra.
Increased serum levels - pregnancy
Interfering factors causing decrease of serum concentrations drugs - isoniazide
increase - oral contraceptives
Biochemical interactions:
vitamin B3 dosing can affect some biochemic values:
Serum
ALP, ALT, apolipoprotein A-I, glucose, GGT, HDL-cholesterol, histamin, insulin,
catecholamines, uric acid, growth hormone
 beta-lipoprotein, total cholesterol, LDL-cholesterol, P, phospholipids, pre-beta LP, TAG,
VLDL cholesterol, FFA
urine
 glucose, ketones, Na
K
Riboflavin
vitamin B2, coenzymes FMN (flavinmononukleotide, riboflavinmonophosphate ), FAD
(flavinadenindinukleotid, riboflavinadenosindifosfát)
C17H20O6N4
Mh: 376,4
-flavinmononukleotide (FMN) or
flavinadendinukleotide (FAD) are active forms
- dehydrogenases and oxidases
- redox processes (oxidative phosphorylation,
synthesis and degradation of FA)
- part of important enzymes (xantin oxidases,
gluthathionreductases, amino acid oxidases
Sources
Cheese, egg, liver, meat, broccoli, parsley, yeast, milk products
Riboflavin
Riboflavin metabolism
Riboflavin
Riboflavin as cofactor
Riboflavin
Function
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electrone transport in Krebs cycle
oxido-redukction processes in aminoacids, sachcarides, purines and pyrimidines
integrity of cell membrane and erythrocytes
antioxidant function (glutathionreductase cofactor)
detoxication of drugs and xenobiotics
Deficiency symptoms
corneal and conjunctival inflammation, neurologic diseases, ariboflavinosis – delayed
growth and high risk of epitelial inflammation
Decreased serum levels
Chronic alcoholism, anorexia nervosa, coeliac disease, dermatosis, hypothyreosis,
stress, infectious enteritis, conjunctivitis, malabsorption, tumors, low protein diet with
high sacharide intake, bile duct obstruction, liver diseases, chronic diarrhoea, gut
resection, dermatitis, pregnancy, sprue.
Vitamin B12
alpha-(5,6-Dimethylbenzimidazolyl)cyanocobamide, CN-kobalamin, adenosylkobalamin
(AdoCbl) a metylkobalamin (MeCbl)
C63H88O14N14PCo
Mh: 1355,4
-syntetized in microorganisms
- target organs - liver (ca 50 %;
3 – 5 mg), muscles and kidney
Sources
- meat, liver, milk products, yeast
droždí.
- Cooking significantly eliminate B12
activity
Vitamin B12
Active metabolites
R
Me- B12
CH3
Metylcobalamine
AdoB12
5´deoxyadenosine
Deoxyadenosylkobalamine
OHB12
OH
Hydroxykobalamine
CN- B12
CN
cyanokobalamine
Active
cofactors
Therapeutic
forms
Deficiency
Deficiency in diet or malabsorption, drug and alcohol
interaction
4 stages
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decrease of plazma concentration
decrease of intracelular concentrations
metabolic impairment
clinical manifestation of deficiency
Vitamin B12
Signs of deficiency
● megaloblastic anemia
● pernicious anemia
● methionine metabolism disorders (impaired DNA synthesis with abnormal formation of
nuclear erythrocytes – storage of megaloblasts in bone marrow)
● impaired purine and pyrimidine synthesis
● homocystinuria
● methylmaloate aciduria
● parestesia, orientation disorders due to impaired myelin synthesis
● confuseness, bradypsychie
● depression
● memory weakness
Vitamin B12
Therapeutical efects
● parenteral application is not approved (anaphylactic reactions).
● in elderly substituion is questionable
● during substitutional therapy control of serum K, Fe, folate, hemoglobin,
MCV, retikulocytes levels is necessary.
● thromboembolic complication in patients with heart ailment
● interpretace of vitaminu B12 concentration is related to folate concentration in
erythrocytes
• Schilling test is performed in cases of impaired vitamin B12 resorption
(chronic gastritis, intestinal deficiency).
● Suspect defficiency is associated with increased methylmalonate and homocysteine
excretion
Vitamin B12
Functions
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antipernicious effect
erythrocyte maturation
neuronal function
DNA/RNA synthesis cofactor
cellular proliferation
hemathopoiesis
myeline synthesis
nucleoprotein formation
enzymatic reaction (metylmalonyl-CoA mutase, methylation)
valine metabolism
folate coenzyme recyclation
Vitamin B12
Why investigate vitamin B12 levels?
● diferential diagnosis of megaloblastic anemias to avoid: CNS disorders, chronic
stomach insuficiency with mucous athrophy after resection, intestinal parasitie
diseases, chronic liver and kidney failure, in vegetarians
Decreased serum levels
Achlorhydria, alphaa-thalasemia, chronic alkoholism, anemia, dementia,
divertikulotitis of the jejunum, cystická fibrosis, gastrectomy, chronic atrophic
gastritis, delirium, hemodialysis, hypermetabolic states, hyperthyreosis, primary
hypothyreosis, chronic pancreatitis, pankreatic insufficience, smoking, leukemia,
malnutrition, multiple myeloma, intestinal tumors, drugs
Vitamin B12
Elevated serum levels
Liver cirrhosis, diabetes mellitus, liver dystrophia, acute and chronic hepatitis,
induced cholestasis, leukemia, leukocytosis, protein malnutrition,
myeloproliferative disorders, chronic renal failure, congestive heart failure, elevated
erythrocyte count, tumors with liver metastases, uremia.
Interfering factors increased serum concentrations
drugs- anticonvulsives, estrogens, vitamin A, vitamin C.
Intrinsic factor and vitamin B12
IF is secreted by parietal cells in upper part of the stomach
- Inevitable role in vitamin B12 absorption from diet
Macrocytic
anemia
Folate
determination
Vitamin B12
determination
low B12
Normal B12
IF Ab
investigatio
n Pernicious
Algorithm of B12 investigation
Plasma tHcy
tHcy > URL
tHcy < URL
Folate and vitaminu B12 in serum
Folate > 7.5 nmol/l and B12 > 200
pmol/l
No deficiency
URL – upper reference limit
Folate < 7,5 nmol/l
Folate deficiency
B12 < 200 pmol/l
Vitamin B12 deficiency
Folic acid
Pteroyl-L-glutamic aqcid, vitamin M, tetrahydrofolate, 10-formyltetrahydrofolate, 5metyltetrahydrofolate
C19H19O6N7
Mh: 441,4
-Active resorption in proximal part of
small intestine
- transport as free form or coupled with
albumin
-Resorption is associated with inteatinal
mucose
- target organ - liver
Sources
Yeast, leaf vegetable, nuts, liver, kidney, orange juice
Structural forms
Folic acid
Folic acid
Folic acid metabolism
Folic acid
Function
● methionin synthesis (synergy with B12)
● normal function of erythrocytes and leukocytes
● coenzyme in purine synthesis
● DNA synthesis
● conversion of homocysteine to methionine
● conversion of serine and glycine
● histidine degradation
● cellular growth and differentiation
● important role in lipid metabolism
● anticancerous efect
● neural tube deffects prevention (1 month before conception 4 – 5 mg of folic acid
until the end of thirt month of gestation).
Folic acid
Deficiency symptoms
-megaloblastic anemia
-pernicious anemia in pregnancy
-neural tube defects in pregnancy
-cardiovascular diseases
Signs of deficiency
Macrocytic anemia, trombocytopenia, defects of digestion (tongue burn,
mucosal inflammation, diarrhoea, ulceration), depression, psychic instability
Folic acid
Increased utility of folates
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alcoholism,
wound healing and regeneration
pregnancy
energetic metabolism
Therapeutic dosing of folate
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megaloblastic anemia
malnutrition
malabsorption
alcoholism
neurological diseases
Folic acid
Decreased serum levels
Alcoholism, amyloidosis, anemia, anorexia nervosa, liver cirrhosis, coeliac disease,
Crohn disease, vitamin B and C deficiency, dermatitis herpetiformis, diabetes mellitus,
peritoneal dialysis, diabetic enteropaty, partial gastrektomy, hemodialysis, chronic
hemolysis, hepatoma, starving, homocystinuria, hyperthyreosis, hypothyreosis,
infectious diseases, breast feeding, leukemia, lymphoma, folate malabsorption,
smoking,dermatitis, chronic heart disease
Increased serum levels
Vitamin B12 deficiency, transfusion vegetarianism
Interfering factors decreasing derum concentrations
Alcohol, aminopterine, ampicoilin, antiepileptics, antimalarics, azulfadin, barbiturates,
cycloserin, erythromycin, estrogens,phenobarbital, fphenytoin, chloramfenicol,
isoniazid, karbamazepin, oral contraceptives, acetylsalicilate, metformin, methotrexat,
nitrofurantoin, penicillin, pentamidin, sulfasalazin, tetracyklin, triamteren.