Lecture 17 - micronutrients part 4 Flashcards
What foods is iron found in?
a lot of different foods at low levels
rich in liver, meats and plant sources
What are the two forms that iron can be found in foods?
- heme - within the porphyrin ring of hemoglobin and myoglobin) - animals
- non-heme - plants
What are the two states that iron can be found as in the body and in food?
Fe3+ (ferric) and Fe2+ (ferrous)
What are the three functions of iron in the body?
- oxygen transport
- redox rxns - active component of ETC
- iron metalloenzymes
Is iron RDA higher in men or women?
women due to menses
how much of the iron we ingest is absorbed?
10-18%
How is non-heme iron absorbed?
HCl and proteases cleave non-heme iron from food components in the stomach to release mostly ferric iron
the acidic environment of the stomach converts most Fe3+ into ferrous
any remaining fe3+ is reduced into Fe2+ by a reductase enzyme in the small intestine
Fe2+ is taken up into the intestinal cells by the divalent metal transporter1 (DMT1)
How is heme iron absorbed?
released from hemoglobin/myoglobin by proteases in the stomach and small intestine
heme is taken up in the small intestine by heme carrier protein (HCP1)
inside intestinal cells, the heme porphyrin ring is broken down by heme oxygenase, releasing Fe2+ and protoporphyrin
How is Fe2+ used once absorbed?
either used in intestinal cells (stored) or transported through blood via ferroportin
What are factors that influence iron absorption?
chelators
enhancers
inhibitors
What are chelators?
small organic compounds that form a complex with a metal ion
- this can affect iron absorption
- if the iron-chelate is soluble , then absorption is enhanced
- if the iron-chelate is insoluble, then absorption is inhibited
What are some examples of enhancers?
vit C (reducing agent) and some evidence for pectin
What are some examples of inhibitors?
polyphenols (in tea and coffee), oxalic acid (in spinach), and insoluble fibres
How is iron transported in the blood?
in the ferric Fe3+ form bound to transferrin (carrier protein)
Why is it important that iron is bound by a carrier?
unbound ferrous iron has a high redox activity and can readily lose an electron, increasing free radical production
What are the steps to iron absorption and attachment to transferrin?
- in SI, Fe2+ converts to Fe3+ once absorbed by ferroportin
- transferrin binds to Fe3+
- oxidation of Fe2+ by ceruloplasmin necessary to attach iron to transferrin
- transferrin receptor binds to transferrin Fe3+ complex
- Fe3+ is reduced by NADPH, FADH2, Vit C
What is ferritin?
iron storage protein - iron is readily available from ferritin
What is hemosiderin?
complex of ferritins and denatured proteins found mostly in macrophages that engulfed RBC’s iron is poorly available from hemosiderin
How is heme formed steps?
- glycine + succinyl CoA uses B6 to become 5-amino levulinate
- 5-amino levulinate becomes porphyrin
- porphyrin uses Fe2+ to make heme
- heme can go to cytochromes, hemoglobin or myoglobin
What are two heme-dependent enzymes?
- catalase (an enzyme in out oxidant defense system) - concerts H2O2 to H2O
- thyroid peroxidase - addition of iodides to thyroglobulin protein
Why is iron important in heme?
iron is critical due to its presence in heme, which enables transport of e- through ETC (cytochrome), oxygen transport to tissues (hemoglobin) and oxygen storage within a tissue (myoglobin)
What are the four groups that iron deficiencies are seen in?
- infants and young children
- adolescents in their early growth spurts
- females during childbearing years
- pregnant women
What are the general symptoms of an iron deficiency?
fatigue, pallor, weakness, hair loss, irritability, brittle or grooved nails, impaired immune function
what are the short term consequences of iron deficiency in fetal development/early childhood?
- lower test scores on mental development
- lower test scores on moto development
- some improvements in test scores after treatment with iron
What can occur if there is an iron toxicity?
- hemochromatosis - increased iron absorption
- hemosiderosis - iron deposition in tissues
- can be treated with iron chelators and blood letting
Where is copper found in foods?
content varies widely in foods
- oysters, shellfish, whole grains, beans, nuts, potatoes, organ meats, dark leafy greens
What is copper sensitive to?
how food is produced and handled
What is coppers function as a component of many important enzymes?
- ceruloplasmin - necessary for iron metabolism
- cytochrome c oxidase - key enzyme in ETC
- superoxide dismutase - necessary for oxidant defense system
- dopamine monoxygenase - norepinephrine production
- tyrosinase - involved in melanin formation
- acts as an enzyme cofactor in many redox
How is copper digested?
Cu2+ is bound to AA, HCl and pepsin release Cu2+
How is copper absorbed?
specific transporters
Where is copper absorbed?
small intestine
What must copper turn into to be absorbed?
Cu2+ must be reduced to Cu1+ to be absorbed
What are the enhancers and inhibitors for copper?
enhancer chelators
inhibitor chelators - high levels of metal ions in the diet promote the production of metallothionein which binds all metal ions and prevents absorption
Where is absorbed copper transported?
to liver bound to protein where it gets incorporated into ceruloplasmin
What disease can be caused by a copper deficiency?
menke’s disease (kinky hair syndrome)
- X linked genetic disease (mutation in the ATP7A gene on X chromosome) inborn error of metabolism in which the body cannot absorb enough copper
what are the symptoms of Menkes disease
anemia, hypopigmentation of skin, bone abnormalities, thrombosis
How can Menkes disease be treated?
copper supplements
What disease can be caused by copper toxicity?
wilson’s disease
- caused by a buildup of copper in body
- normally excess cu excreted in bile, people who have wilsons cannot do this, due to mutation in ATP7B gene
- cu accumulates in other organs, brain, kidneys and eyes
What are the symptoms of Wilson’s disease
drooling
slurred speech
problems swallowing
problems walking
cognitive impairment
What are the treatments for Wilson’s disease?
low copper diet
chelation therapy
zinc therapy
Where is zinc found in the body?
found in all organs, tissue sand body fluids - typically as Zn2+
What are some zinc food sources?
oysters, red meat, poultry
What are three functions of zinc?
- zinc containing metalloenzymes - provide structural integrity (stabilizes tertiary protein structure) and/or plays a role at reaction site of enzyme
- oxidant defense system
- DNA binding (formation of zinc fingers)
What must be done to zinc in order for it to be absorbed?
zinc must be released from AA, done by HCL in stomach and digestive enzymes in SI
what are the two mechanisms which zinc can be absorbed by?
- carrier-mediated (ZIP4 primary mechanism)
- simple diffusion
What are the enhancers and inhibitors of zinc?
enhancer chelators - organic acids, prostaglandins
inhibitor chelators - antacids, phytic acid, oxalic acid, metallothionein
Why is there a higher zinc RDA in males?
support testosterone function
What occurs if there is a zinc deficiency?
- common in humans
- poor absorption can be caused by phytic acid in grains
- in children, zinc deficiency can slow growth (inadequate cell division), poor wound healing, delayed sexual maturation (deficient testosterone synthesis), and impaired taste (insufficient taste proteins)
What happens if there is a zinc toxicity?
- neurological problems, numbness metallic taste, nausea
- causes cu deficiency due to the activation of metallothionein
