Transcript Biochemistry of nutrition,vitamins

Bruno Sopko
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Introduction
Macronutrients
◦ Aminoacids, proteins
◦ Carbohydrates
◦ Fatty acids, cholesterol
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Regulation of macronutrient uptake
Micronutriets
◦ Fat-soluble vitamins
◦ Water-soluble vitamins
◦ Minerals
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Energy and nutrition homeostasis
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Exogenous Inputs–Environmental Signals
Metabolic Signals
Endocrine Signals
Neural Signals
Genes and Gene–Environment Interactions
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Aminoacids, proteins
Carbohydrates
Fatty acids, cholesterol
Fiber
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Digestion, absorption of the proteins
Protein turnover
Essential aminoacids
Interorgan cooperation
AA transport into the cell
Regulation of AA metabolism - anabolic
Regulation of AA metabolism - catabolic
Effect of AA on glucagon and insulin
secretion
Nitrogen balance
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Glucagon activates phenylalanine hydroxylase
by an adenosine 3′5′-cyclic monophosphate
(cAMP)-dependent mechanism.
Glucagon activates glutaminase and the
glycine cleavage enzyme, although the
mechanism of these effects remains obscure.
Glucagon and glucocorticoids induce the
synthesis of a number of amino acid
catabolising enzymes.
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Carbohydrates – intake
Carbohydrates - regulation
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Adipose tissue hormones
◦ Leptin
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Panecreatic hormones
GIT hormones
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Glucagon
Insulin
Pancreatic Polypeptide
◦ Reduces apetite by unknown mechanism
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Amylin
◦ Reduces food intake
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Ghrelin (produced mainly by
P/D1 cells lining the fundus of
the human stomach and
epsilon cells of the pancreas)
◦ appetite-regulating hormone
(leptin antagonist)
◦ growth hormone secretagogue
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Peptide YY (ileum and colon)
◦ potential proabsorptive hormone
◦ reduce appetite
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Incretins : Glucagon -Like
Peptides (GLP-1,2) and Glucose
-Dependent Insulinotropic
Peptide (gut)
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Oxyntomodulin (Parietal cells - stomach epithelial cells that secrete
gastric acid (HCl) and intrinsic factor)
◦ suppress appetite
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Cholecystokinin (I-cells in the mucosal epithelium)
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Bombesin - like Peptides
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Apo A-IV (intestine)
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Enterostatin (intestine by pancreatic procolipase)
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Obestatin (produced from the same prohormon as ghrelin)
◦ release of digestive enzymes and bile from the pancreas and gallbladder
◦ hunger suppressant
◦ inducing drug tolerance to opioids
◦ gastrin-releasing peptide (GRP)
◦ Neuromedin B (NMB)
◦ activate lecithin-cholesterol acyltransferase and cholesterylester transfer
protein in vitro;
◦ play a role in the regulation of appetite and satiety in rodent models;
◦ display anti-oxidant and anti-atherogenic properties in vitro and in rodent
models;
◦ modulate the efficiency of enterocyte and hepatic transcellular lipid transport
in vitro.
◦ reduction of insulin secretion
◦ increase in sympathetic drive to brown adipose tissue
◦ stimulation of adrenal corticosteroid secretion
◦ initiates a sensation of fullness of stomach
◦ antagonise growth hormone secretion and food intake induced by ghrelin
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Lipid soluble vitamins
◦ Vitamin A
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Water soluble vitamins
Minerals
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hydrophobic compounds, absorbed efficiently
with lipids,
transport in the blood in lipoproteins or
attached to specific binding proteins,
more likely to accumulate in the body,
more likely to lead to hypervitaminosis
Retinol
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Biologically active forms retinoids: retinol, retinal,
retinoid acid.
Major vit. A precursors
(provitamins) → plants
carotenoids.
Foodstaf of animals origin
contain most of vit. A in the
form of esters (retinylpalmitates) – retinol and long
fatty acid
Cyklohexan ring and isoprenoid
chain
 Retinol esters → hydrolysis by
pancreatic enzymes to retinol.
 b-caroten is cleaved to retinal by bcarotene 15,15´ dioxygenase
(cofactors iron and bile salts).
 Intestinal cells → esterification of
retinol → transported in
chylomicrons.
 Remnants of chylomicrons →
liver→ esterification (if the
concentration exceeds 100 mg,
esters are stored ).
 Transport of retinol to target
organs tightly bound to retinolbinding protein, RBP.
Transcription and cell differentiation
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Retinoic acid regulates the transcription of genes - acts through
nuclear receptors (steroid-like receptors).
Retinol
retinal
Retinol dehydrogease
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retinoic acid
Retinaldehyde dehydrogenasa
By binding to various nuclear receptors, vit. A stimulates (RAR –
retinoid acid receptor) or inhibits (RXR- retinoid „X“ receptor)
transcription of genes transcription. All-trans-retinoic acid
binds to RAR and 9-cis-retinoic acid binds to RXR.
Retinoic acid is necessary for the function and maintenance of
epithelial tissues.
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Vision
Gene transcription
Immune function
Embryonic development and reproduction
Bone metabolism
Haematopoieis
Skin health
Antioxidant activity
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cod liver oil
meat
egg
milk
dairy
products
 carrot
 broccoli
 spinach
 papaya
 apricots
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Calciol, vitamin D2 (cholecalciferol) → precursor
of calcitriol, D3 (1,25-dihydroxycalciferol).
Regulates with PTH calcium and phosphate level
(absorption, reabsorption, excretion).
Synthesis in the skin (7-dehydrocholesterol) UV
→ further transformation in the liver and
kidneys .
In addition to sunbathing:
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various fish species (salmon, sardines and mackerel, tuna,
catfish, eel), fish oil, cod liver
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eggs, beef liver, mushrooms
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Absorbed with the food fats and is dependent on the
presence of the bile salts (any disease which resulted in an
impairment of fat absorption likewise resulted in an
impairment of vitamin D absorption)
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Absorption is a passive process which is influenced by the
composition of the gut contents.
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Absorbed with the long-chain fatty acids and is present in
the chylomicrons of the lymphatic system.
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Vitamin E is a famil of a-, b-, g-, d- tocopherols
and corresponding tocotrienols izomers.
They are formed from chroman ring and
hydrofobic fytyl side chain.
The highest biological activity has a-tokoferol.
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Absorbtion from the small intestine (50 %)
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Its absorption is dependent on the presence of lipids
in the diet.
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Associated with plasma lipoproteins → liver uptake
through receptors for apolipoprotein E.
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a-tocopherol is bind to a-tocopherol transport
protein (a-TTP) → transported to the target organs
(the excess is stored in adipocytes, in muscle, liver).
b-, g- a d-tocopherols are transferred into the bile
and degraded.
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fortified cereals
seeds and seed oils, like sunflower
nuts and nut oils, like almonds and hazelnuts
green leafy vegetables,
broccoli
cabbage
celery
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Vitamin K is a group of lipophilic, hydrophobic
vitamins.
They are needed for the postranslation
modification of proteins required for blood
coagulation,
They are involved in metabolism pathways, in
bone mineralisation, cell growth, metabolism of
blood vessel wall.
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Vitamin K1
Vitamin K1 (phylloquinon) –
plant origin
Vitamin K2 (menaquinon) –
normally produced by bacteria
in the large intestine
K1 a K2 are used differently in
the body
Vitamin K2
◦ K1 – used mainly for blood
clothing
◦ K2 – important in noncoagulation actions - as in
metabolism and bone
mineralization, in cell growth,
metabolism of blood vessel
walls cells.
Synthetic derivatives of Vit.K
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Green leafy vegetables
vegetable oil
broccoli
Cereals
The absorption of K1 and K2 analogs occurs via an
active, energy-dependent transport process, whereas
K3 (menadione) analogs are absorbed by passive
diffusion.
Vitamin C
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Vitamin C is a water-soluble vitamin.
Almost all animals and plants synthesize their
own vitamin C, not man.
Vitamin C was first isolated in 1928 and in 1932
it was proved to be the agent which prevents
scurvy.
Vitamin C
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Vitamin C is a weak acid, called ascorbic acid or
its salts “ascorbates”.
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It is the L-enantiomer of ascorbic acid.
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The D-enantiomer shows no biological activity.
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Absorbed in the small intestine, primarily the
ileum, by an active transport system - both
sodium dependent and energy dependent.
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Cytochrome P450 oxidases (several)
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Dopamine-β-monooxygenase
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Peptidyl glycine α-amidating monooxygenase
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Cholesterol 7-α-hydroxylase
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4 Hydroxyphenylpyruvate oxidase
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Homogentisate 1,2-dioxygenase
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Proline hydroxylase
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Procollagen-proline 2-oxoglutarate-3-dioxygenase
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Lysine hydroxylase
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γ-Butyrobetaine, 2-oxoglutarate-4-dioxygenase
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Trimethyllysine-2-oxoglutarate dioxygenase
Deficiency of vitamin C
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Fatigue, personality changes, decline in psychomotor
performance and motivation.
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Vitamin C deficiency over 3-5 months results in
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symptomatic scurvy.
Scurvy leads to the formation of liver spots on the
skin, spongy gums, and bleeding from all mucous
membranes.
In advanced scurvy there are open, suppurating
wounds and loss of teeth. Severe scurvy may progress
to neuritis, jaundice, fever, dyspnea, and death.
Absorption
Place
B1-thiamine
specific active transport
mechanism
small intestine
B2-riboflavin
active carrier and is
energy and sodium
dependent
jejunum
B3-niacin
simple diffusion and
facilitated diffusion
small intestine
B5-panthotenic acid
facilitated diffusion
small intestine
B6
facilitated
diffusion may exist
small intestine
B7-biotin
facilitated diffusion
jejunum
B9-folic acid
carrier-mediated, pHdependent
jejunum
B12-cobalamin
B12 is bound to a carrier
protein
called intrinsic factor
distal portion of the
ileum
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Choline
Carnitine
Inositol
Pyrroloquinoline Quinone
Ubiquinone
Orotic Acid
Para-Aminobenzoic Acid (PABA)
Lipoic Acid
Bioflavinoids
Pseudovitamins
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Sodium
◦ Transported with other compounds
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Potasium
◦ Passive transport
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Chloride
◦ Passive transport
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Calcium (20% - 50 %)
◦ Vitamin D dependent
◦ Passive diffusion
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Phosphorus
◦ Active, saturable, sodium-dependent mechanism
(vitamin D)
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Magnesiun (30 % - 70 %)
◦ Passive diffusion
◦ Active diffusion
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Iron
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Zinc
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Copper
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Selenium
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Iodine
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Molybdenum
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Manganese
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Cobalt
◦ Haem bound
◦ Free
◦ Lactoferrin
◦ passive
◦ diffusion while the latter may involve the zinc-binding metallothionein protein and/or
a cysteinerich
◦ intestinal protein
◦ Active diffusion
◦ Selenocysteine
◦ Iodide ion, diffusion
◦ Diffusion
◦ Unknown
◦ interfere with the absorption of iron and in fact can completely block iron
uptake
◦ cobalamin
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Pyruvate carboxylase
Acetyl CoA carboxylase
Isocitrate dehydrogenase
Mitochondrial superoxide dismutase
Arginase
Glucokinase
Galactose transferrase
Hydroxymethyl transferase
Superoxide dismutase
Literature
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Thomas M. Devlin ed. Textbook of
biochemistry with clinical correlations, Fourth
edition (1997), Wiley and sons.
Christos S. Mantzoros, NUTRITION AND
METABOLISM, Underlying Mechanisms and
Clinical Consequences (2009), Humana Press,
a part of Springer Science+Business Media
Carolyn D. Berdanier (1998), ADVANCED
NUTRITION, Micronutrients
Others are cited directly on the pages