Term
| Iron Assessment Tests (7) |
|
Definition
Hemoglobin
Hematocrit
Serum iron
Serum ferritin (the storage protein)
Total Iron Binding Capacity (TIBC)
Transferrin saturation
Zinc protoporphyrin heme ratio (can detect iron changes on a day to day basis—very sensitive)
^ zinc is incorporated in heme |
|
|
Term
| What is hepcidin and what is its role? |
|
Definition
Hepcidin –
Peptide hormone secreted by liver
Reduces ferroportin expression in enterocytes (inhibits iron export into bloodstream)
In iron deficiency, hepcidin levels are low
In iron overload, hepcidin levels are high |
|
|
Term
| Describe the body's deliberate physiological changes during iron deficient state (3) |
|
Definition
DMT-1 expression increased
Ferroportin-1 expression increased
hepcidin levels are low |
|
|
Term
| Signs and symptoms of Iron overload (8) |
|
Definition
| Fatigue, depression, joint pain, increased skin pigmentation, liver disease (cirrhosis, hepatocellular carcinoma), cardiomyopathy, diabetes |
|
|
Term
| What is Hereditary hemochromatosis? (5) |
|
Definition
Hepcidin production problems that occur in 1 in 200 people
Results in increased iron absorption and inappropriate deposition in:
Liver, heart, pancreas |
|
|
Term
| Who is at risk for an iron deficiency? (8) |
|
Definition
Infants and young children
Adolescent girls
Women of childbearing years
Pregnant women
Female athletes
Increased Iron Losses:
Hemmorrhage, renal disease, parasitic infection (pregnant women) |
|
|
Term
| Signs and symptoms of an Iron deficiency |
|
Definition
Fatigue, depression, irritability, pallor, sensitivity to cold, intellectual impairment, decreased resistance to infection
Less Ferritin |
|
|
Term
| What is the most common nutritional deficiency in the world? |
|
Definition
| Iron deficiency; Estimates of ~10% of at risk groups in US, ~30-40% of population in developing countries |
|
|
Term
| General enzymatic reactions that require the presence of vitamin c to reduce iron (4) |
|
Definition
Carnitine synthesis
Collagen synthesis
Phenylalanine hydoxylase, tyrosine hydroxylase |
|
|
Term
| What antioxidant requires iron for proper functioning? |
|
Definition
|
|
Term
| What immune function does iron serve? |
|
Definition
| Myeloperoxidase (makes bleach (hypochlorous acid) to kill) |
|
|
Term
| What two molecules does iron carry O2 in? |
|
Definition
|
|
Term
| What are the two copper containing ferroxidase enzymes? |
|
Definition
| Ceruloplasmin (blood) or hephaestin (intestine) |
|
|
Term
| Where is iron stored in the body? (5) |
|
Definition
Inside cells iron stored in ferritin
In every cell, but mainly in hepatocytes (60%), bone marrow, spleen
Ferritin consists of 24 subunit globular protein
H and L subunits
Stores up to 4500 iron atoms in core |
|
|
Term
| What cells can release Iron from ferritin? (3) |
|
Definition
| Enterocytes hepatocytes and macrophages |
|
|
Term
| What must happen before iron is released from ferritin? |
|
Definition
| Release of iron from ferritin requires reduction to ferrous state |
|
|
Term
|
Definition
| Degradation product of ferritin; present in iron overload |
|
|
Term
| Which ion binds to transferrin? |
|
Definition
|
|
Term
| What are the enhancers of iron absorption? (9) |
|
Definition
Acids
HCl, ascorbic, citric reduce ferric to ferrous iron
Meat, fish, poultry (MFP)
Cysteine containing peptides help solubilize iron
Mucin
Secreted by stomach and intestine; thought to chelate iron
Iron deficiency (low iron status) |
|
|
Term
| What are the inhibitors of iron absorption? (12) |
|
Definition
Competitors for transport
Calcium, zinc, manganese, nickel
Formers of insoluble complexes
~ she said something about ‘Calcium’, oxalic acid, phytic acid, tannins
Physiological states
Reduced stomach acidity (can be induced by antacids), rapid transit time, good iron status |
|
|
Term
| What do DMT1 and DCYTB stand for and what are their roles? |
|
Definition
Duodenal cytochrome b (DCYTB) reduces ferric iron to ferrous iron
Divalent metal transporter 1 (DMT1) - absorbs ferrous iron |
|
|
Term
| Roughly what percentage of heme iron is absorbed? Non-heme iron? |
|
Definition
30% of heme iron is absorbed
Non-heme iron absorption – (not as efficient ~ 10%) |
|
|
Term
|
Definition
Hydrolyzed from hemoglobin or myoglobin by proteases in stomach and small intestine
Absorbed intact in a receptor mediated fashion (heme carrier protein)
Heme oxygenase degrades heme and frees iron INSIDE enterocyte |
|
|
Term
|
Definition
| Another name for R protein -- the protein that binds to b-12 in the STOMACH |
|
|
Term
| Explain the roles of Transcobalamin I and II (TcI, TcII) |
|
Definition
TcI is used for storage; made in liver
TcII is used for transport out of enterocytes to liver |
|
|
Term
| What is the protein name for b-12 receptor protein? |
|
Definition
| cubulin/megalin (both names refer to the same protein) |
|
|
Term
| Describe the process of b-12 absorption (9) |
|
Definition
in stomach:
Hcl denatures protein and activates pepsin
Pepsin breaks down protein releases b-12
R protein in stomach binds to b-12
IF released
In Ileum:
proteases breakdown R protein where b-12 then binds to IF
cubulin/megalin or vitamin b-12 receptor
in enterocyte b-12 binds to Transcobalamin II (TcII) in golgi apparatus
it then goes to liver where it is taken up or moves on to other tissues
the liver also produces TcI (used for storge) |
|
|
Term
| What form of THF is required for purine synthesis? Pyrimidine synthesis? |
|
Definition
Purine – 10 formyl THF
Pyrimidine 5, 10 methyl THF |
|
|
Term
| What leads to Macrocytic, megaloblastic cells in b-12 and Folate Deficiencies? |
|
Definition
| Folate is required for purine and pyrimidine synthesis which are required for nucleotide production, which are required for proper DNA replication which leads to the inability of erythrocytes to mature properly. |
|
|
Term
|
Definition
| Red Blood Cell Production. |
|
|
Term
| Name the rxn that thymidylate synthetase is responsible for? |
|
Definition
| deoxyuridylate (dUMP) --> deoxythymidylate (dTMP) |
|
|
Term
| What rxn is the MTHFR (motherfucker) responsible for? |
|
Definition
| N5,N10 methylene THF + NADPH + FADH2 --> N5 methyl THF + NADP + FAD |
|
|
Term
| B-12 Assessment Tests (4) |
|
Definition
Serum B12
Serum homocysteine
Deoxyuridine suppression test
Serum or urine methylmalonoic acid |
|
|
Term
| Who is at risk for a b-12 deficiency? |
|
Definition
Older population (due to reduced stomach pH)
Those with atrophic gastritis
Vegans
Kids breastfed by B12 deficient Moms
Those with a gastrectomy
Those with malabsorption |
|
|
Term
| What are the signs and symptoms of a b-12 deficiency? |
|
Definition
Pernicious Anemia -- Autoimmune depletion of IF
Megaloblastic anemia
Clinical features
Pallor, fatigue, shortness of breath
Paresthesia, altered gait
Memory loss, disorientation, delirium, dementia
Neurological symptoms frequent
SAM deficiency in nervous system
Not in notes:
Depression commonly associated
Asthma commonly associated
Low blood cell count (as part of pernicious anemia) |
|
|
Term
| What other enzyme besides met synthase requires b-12 and what does this enzyme do? |
|
Definition
MethylmalonylCoA Mutase – uses 5’ adenosylcobalamin
methylmalonyl-CoA --> succinyl-CoA
we don't need to know: required for the complete processing of BCAAs, odd chain fatty acids, thymine, and cholesterol |
|
|
Term
| Describe the excretion of b-12 (3) |
|
Definition
Not degraded
Most excreted bound to R protein via bile
Little urinary excretion |
|
|
Term
| What are the three forms of b-12 consumed? |
|
Definition
Cyanocobalamin - supplemental
Methylcobalamin – transport form
Hydroxycobalamin – storage |
|
|
Term
| Folic Acid; Digestion and Absorption (8) |
|
Definition
-Monoglutamate form is absorbed
-Hydrolysis of polyglutamate forms of folate via conjugases to monoglutamate form
Pancreatic conjugases
Membrane bound (Zn dependent)
Conjugase inhibitors in legumes, cabbage, and oranges
Carrier mediated, FBPs
In enterocyte, reduction to THF and methylated to 5-methyl THF
Carrier mediated exit from enterocytes
50% of food folate absorbed
Supplemental folate absorption is higher than from foods
1 dietary folate equivalent (DFE) = 1 mg food folate, or 0.6 mg fortified foods, or 0.5 mg supplemental folic acid (taken on empty stomach) |
|
|
Term
| Folate transport:Transport in portal circulation (3); Transport in circulation (1); Transport into Cells (3) |
|
Definition
Transport in portal circulation
Mainly 5-methyl THF - monoglutamate form
Receptor mediated uptake into hepatocytes
Folylpolyglutamate synthetase adds glutamate residues
Transport in circulation
Mostly as FBP-bound monoglutamate form (5-methyl THF)
Transport into cells
Carrier mediated
Polyglutamated in cells
Liver, kidney, hematopoietic cells |
|
|
Term
|
Definition
Liver contains most of body pool of folate
Enterohepatic circulation |
|
|
Term
|
Definition
Urinary excretion
Some intact, some metabolized
Fecal excretion - minimal
Folate secreted into bile |
|
|
Term
|
Definition
-Amino acid metabolism
Serine synthesis from glycine
Glycine degradation
-Histidine catabolism (FIGLU formation)
-Methoinine synthesis from homocysteine.
-Nucleic acid metabolism
Purine and pyrimidine synthesis |
|
|
Term
| Folate Deficiency Signs and Symptoms (6) |
|
Definition
-Gradual onset of symptoms
3-4 months to deplete stores so that tissue levels reduced
4-5 months – can’t make DNA, results in abnormal division of cells (red cells, enterocytes)
-Symptoms – weakness, fatigue, headache, irritability
-Megaloblastic anemia
-Neural tube defects |
|
|
Term
| Who’s at risk for a folate deficiency (3) |
|
Definition
-Diminished absorption
-Increased requirement – pregnancy, infancy, malignancy
-Genetic variants of MTHFR
50% reduction in activity
Increased risk of stroke, CHD, depression |
|
|
Term
|
Definition
-High dose supplementation may mask B12 deficiency.
This would cure the anemia, but would not address the neurological disturbances. |
|
|
Term
| Folate Status Assessment (3) |
|
Definition
-Plasma folate
Reflects recent dietary intake
-Red blood cell folate levels
-FIGLU excretion
Following histidine load |
|
|
Term
|
Definition
Formiminoglutamic acid (FIGLU) is an intermediate in the metabolism of histidine.
Used to test for b-12 or folate deficiency, or liver disease. |
|
|
