Chapter 6: Anorganic nutrients

Anorganic nutrients

General principles

• Alkali metals are completely filtered by glomerulus

• Vegetable foods are rich in K

• Trace-element are less bioavailable in vegetable foods

• Meat is rich in Na and trace elements, poor in Ca, Ca/P «1

• Cows milk rich in Ca, but poor trace elements

• Strong regulation in uptake and excretion

Salt intake

Important food sources

• Meat and meat analogues

• Cereals and cereal products

• Milk products and subsitutes

• Spices and sauces

Na intake is underestimated: salt addition during preparation or added at the table are not taken into account

Macro - elements: Sodium, potassium and chlorine

Macro-element	Location	Function
Na+	extracellular, skeleton	Absorption: active transport (Na-K-ATPase) Excretion: urine (low) + sweat
K+	intracellular	Absorption: active transport (Na-K-ATPase)
Cl-	extracellular, gastric acid	Absorption: passive or specific transport (cystic fibrosis) Excretion: gastric juice

Na absorption

1) Decrease of plasma Na + blood pressure → release of renin and angiotensin II in the bloodstream

2) Angiotensin II stimulates synthesis of aldosteron in the adrenal cortex

3) Increased absorption of Na by jejenum and ileum (angiontensin II) + increased reabsorption of Na by colon (aldosteron) + decrease excretion in urine

Hyperkalemia

= too much K in extracellular water → release of aldosteron → increased K-uptake by cells

Hyponatraemia

= sodium levels in the blood are reduced

Hypertension

= high blood pressure

• When sodium intake is higher than recommendation with highly efficient hormonal regulation of the sodium balance

• low intakes of Ca and K stimulate Na-induced hypertension

DASH

= Diet Approach to Stop Hypertension

• lower amount of total and saturated fat and cholesterol

• higher amounts of K, Ca, Mg, fiber and protein

• highest reduction at lowest level of sodium intake

• ↓ = pull strategy, → = push strategy

Macro - elements: Calcium and phosporus

• present in the skeleton:

  • chondroitin

  • osteoblasts (Ca incorporating cells)

  • osteoclasts (Ca mobilizing cells)

• Ca/P proportion = 2/1

Ca	P
kinases calmoduline	buffer nucleic acids ATP

Signal function of ATP

1) Binding of an extracellular stimulant (hormone) to membrane receptor

2) Fosfolipase C ↑

3) Convertion of fosfatidylinonositol-diP in DAG and IP3

4) IP3 can increase the Ca-concentration which, together with DAG, activates a protein kinase C

5) Influence on the cell function

Hormone regulation Ca content in body

• Hormones

  • Calcitonine

  • Parathyroid hormone (PTH)

  • sex hormones

• deregulation → lower osteoblast activity

Ca absorption (Small intestine)

• transcellular absorption: active transport, vitamin D, mainly at low Ca uptake, low for elderly

• paracellular absorption: passive diffusion, mainly at high Ca uptake

• influence of Ca-salts and gastric juice

P absorption (Small intestine)

• duodenum: Na-dependent, vitamin D

• jejenum and ileum: passive diffustion

• better organic than anorganic

Ca excretion → maintain Ca/P ratio

Low free calcium in blood	High free calcium in blood
increase PTH → induces: increase uptake of calcium from the intestine increase uptake of calcium and phosphor from skeleton decrease of Ca excretion	decrease PTH → induces: decrease uptake of calcium from the intestine decrease uptake of calcium and phosphor from skeleton increase of Ca excretion

hyperfosfataemia and hypocalcaemia

hyperfosfataemia	hypocalcaemia
too high phosphate in blood binds to free calcium → induces hypocalcaemia	too low free calcium in blood stimulates PTH release

• Causes: insufficient hormonal regulation or cow’s milk instead of maternal milk

• Who: newborns

• Consequences: less stable bone structure

Ca retention as a function of intake

• supplementation of Ca in children and adolescents → improvement in total bone mineral content in the body

• Sufficient Ca-intake during growing phase of life remains important to develop a sufficient amount of bone mass

• Ca-intake below reference value of 400 - 500 mg/d => osteoporosis

• acid products → osteoclast activity ↓

• physical activity ↓→ osteoclast activity ↓

Solution to maintain bone fraction after bone growth = calcium and vitamin D

Macro - elements: Magnesium

• complex formation with ATP via phosphate

• Na-K ATPase sensitive for Mg shortage

• use against hyperventilation

Macro - elements: Sulphur

• Present in S-containing amino acids and mucines, free sulphate in blood plasma

• Sulphate incorporated via PAPS in tyrosine of secretory proteins

• Role in detoxification, urinary excretion of suphated conjugates

GSH

= Glutathion

• Glu-Cys-Gly

• GSH = protects cells

• GSSG = oxidised form

Metabolism of glutathion

• Reabsorption of AA in the kidneys (glutamyl-transpeptidase)

• Glutathion peroxidase: Detoxification of H2O2 and ROOH

• Thiol transferase: Regeneration of SH-groups in protein and coenzyme A

• Non enzymatic inactivation of radicals

• GSH-S-transferase: Detoxification of carcinogenic epoxides

Trace- or oligo-elements

• Relation to concentration in the body (< 50 mg/kg)

• essentiality: cfr. physiological function

  • Influence analytical methods

  • Different from contamination

  • Difference in requirement for Co or vitamin B12

• Broad spectrum of metabolic activities

Element	Mainly occuring in
Fe	liver blood
Cu	liver eyes blood
Zn	testes
Mn	/
I	thyroid gland
Se	liver kidneys

Classified according to essentiality

• Essential for humans

• Essential for humans with small chance of deficiency

• Essential at extreme low concentrations

Demonstrating essentiality (deficiency) is difficult because it is not only determined by different intakes, but also by

• Differences in absorption determined by the chemical form of the element and interactions with other nutrients

• Differences in excretion depending on the conditions

• Differences in requirements depending on the physiology

• Choice of physiological criterium

  • depletion of reserves in the liver

  • Reduction in serum concentration

  • Metabolic artefacts (enzymatic activity)

  • Clinical symptoms (anemia during Cu-deficiency)

Response = concentration dependent

deficiency zone → optimal zone → pharmocological zone → toxicity zone

Trace- or oligo-elements: Utilisation

→ general model of homeokinesis

1) absorption is

• regulated by saturation level

• regulated by synthesis of transport- and/or storage proteins in the enterocytes

• inhibited by vegetable foods

2) Excretion is

• non-urinary, but difficult (eg. sweat, hair…)

Trace- or oligo-elements: amplifying effect

= large amounts of trace element can cause large biological effects because they act on processes with high turnover

Examples

• Cr → large differences in energy metabolism

• Co → important for protein synthesis

Trace- or oligo-elements: Interactions of trace elements and vitamins in radical formation

Trace- or oligo-elements: Iron

3 unique mechanisms for regulation of iron balance

1) Storage of Fe (ferritin)

2) Reuse of Fe (from erythrocytes)

3) Regulation of Fe absorption

Iron absorption

Luminal phase	Mucosal uptake and transport
Solubilisation of Fe from the food Influence pH and valency (ferrous vs ferri) Stimulation: haem, vitamin C, cystein, organic acids Reduced: phytate, polyphenols and fibre Animal (40% haem) vs vegetable (100% non-haem) food	mucosal block theory Only intracellular transport after saturation of ferritin Transport by transferrin in blood in function of needs

Flow chart iron

• Red blood cell: Fe2+ in center of haemoglobin → oxygen transport

• Muscles: Fe2+ bound to myoglobin

• proteins: Fe3+ bound to these

  • transport

    • transferrin

    • lactoferrin

  • storage

    • ferritin

    • hemosiderin

What to do to improve Fe solubility

1) pH ↓

2) Valency (Fe3+ vs Fe2+)

3) Haem

Trace- or oligo-elements: Iron - Regulation iron absorption and Mucosal block

Low body iron demand → iron stored

1) High plasma iron → liver

2) Hepcidin ↑ → ferroportin (FPN) ↓

3) Iron export to blood ↓

4) Iron concentration in enterocyt ↑ → IRP’s get signal

5) Saturation in enterocyte from iron in ferritin → IRP’s inhibit ferritin and DMT1 transporters

6) When enterocyte is saturated → iron in intestine doesn’t get absorbed

High body iron demand → iron absorbed and mobilized

1) Low plasma iron

2) Hepcidin ↓ → ferroportin (FPN) ↑

3) Iron export to blood ↑

IRP deficient

• ferritin expression is more pronounced with stronger effects of Fe deficiency on DMT1 expression

Trace- or oligo-elements: Iron - How to improve iron status

• Increase in meat consumption

• supplementation with iron tablets

• fortification (adding iron to cereal flours)

• biofortification (enhancing iron content and bioavailability in staple crops = genetic engineering)

Trace- or oligo-elements: Iodine

• T3 = triiodothyronine

• T4 = thyroxine

Thyroid hormones important for

• foetal development

• Regulation metabolic activity

• Heat production

• Thyroid hormones (= tyrosine + iodine) remain bound to thyroglobuline during storage in the thyroid gland

• Proteolytic enzymes: thyroglobuline → blood

• TSH stimulates hormone production + thyrocide hormone

• Blockings

  • (1) Thyocyanates and perchlorates block iodine-uptake

  • (2) thiouracil inactivates oxidizing enzymes

  • (3) sulfonamides interfere in the condensation with tyrosine

Stap	Voldoende jodium	Jodiumtekort (= goiter)
Synthese T3/T4	normale synthese	onvoldoende synthese
Feedback op hypothalamus (thyroid stimulating hormone)	negatieve feedback → TRH ↓	negatieve feedback valt weg → TRH ↑
Hypofyse (thyrotropine stimulating hormone)	TSH-secretion ↓	TSH-secretion ↑
Thyrocyten	normale grootte	hypertrofie + hyperplasie

Trace- or oligo-elements: Selenium

• Toxic element for Se-rich soils

• Se shortage

• Absorption as selenomethionine

• Excretion as urine

• Functions: Selenoproteins

  • anti-oxidant defence and thyroid metabolism

  • cytoplasmatic and membrane (phospholipid) hydroperoxide GPx, selective formation

• Potential link with immune function, intestinal cancers, cardiovascular disease