Magnesium Flashcards
1
Q
Explain the physicochemistry of magnesium
- Is it bound or free floating?
- Why is it unique?
- How abundant is it?
A
- Magnesium functions as divalent ion with atomic weight of 12
- Mg - highly abundant cation. 4th in body overall (after Ca, K, and Na) but 2nd within the cell
- Usually bound to other ligands and molecules (often not available in free form) chelates with anionic ligands to provide support to structures
- Unique in that it can bind to highly charged molecules (anions) that other ions cannot and acts primarily as a stabilizer and ‘complexer’ - often can compete with calcium
- Magnesium has large hydrated volume (compared to calcium) and typically not as flexible in it’s binding state. Prefers to bind than accept
2
Q
How is magnesium distributed through the body and what is its abundance?
A
- 54% in skeleton (540mmol) and 45% in soft tissue (450 mmol). Other 1% in extracellular fluid
- Of extracellular fluid 60^ is free, 30% is protein bound, and 10% is complexed with other macromolecules
3
Q
What are the general physiological functions of magnesium?
A
- Magnesium functions as divalent ion to complex to organic phosphates and nucleic acid
- Mg is essential for effective aerobic and anaerobic metabolism
- Mg is intimately apart of essential functions such as:
1. Cellular energy metabolism (lipid and CHO metabolism)
2. Nucleic acid and protein synthesis (transcription, translation, etc.)
3. Second messenger systems (hormones and neurotransmitters)
4. Ion channel (acts as stabilizer for function of channels)
4
Q
How is magnesium related to ADP/ATP conformation?
A
- Binds to outer phosphate groups allowing to accept/donate phosphate group
- Without magnesium cannot interact with substrates
5
Q
How is magnesium related to glycolysis?
A
- Needed for Steps 1,3,7,9, and 10
- Sometimes interacting with the enzyme themselves, requiring energy or making energy
- Needed for glycolysis to go ahead as it helps with enzyme stabilization
- It is able to make substrates more effective
6
Q
How does Magnesium effect nucleic acids and protein synthesis?
A
- Divalent cations such as Mg2+ bind specifically to phosphate groups on Nucleic Acids
- Phosphate binding allows Mg2+ to be very effective as shielding agents for NA (compared to mono-valent ions). This prevents degradation.
- Mg2+ ion has an influence on the DNA double helix equivalent to that of 100-1000 Na+ ions (Mg likes to bind so less is needed in comparison to Na)
- Most NA or nucleotides require Mg2+ ion for activity and for structural stabilization (helps stabilize helical structure of DNA)
7
Q
How does magnesium impact the Adenylate cyclase system?
A
- Magnesium impacts the Adenylate Cyclase System. Present at nearly every step of the process
- Receptor interfaces with guanine nucleotide-binding protein (G-protein)
- Activation of G-protein sub-units require the presence of both GTP (guanosine triphosphate) and Mg2+
- Mg2+ also thought to bind directly onto G-protein to further enhance activity of the interactions and stabilization within the bilayer
- Mg2+ also required for ATP to drive cyclic AMP link and to provide energy for the Kinase A step
Overall, Mg2+ provides structural integrity to prevent degradation, direct protein interactions with different subunits, and phosphate molecules that need magnesium
8
Q
What second messenger systems does magnesium impact?
A
- Adenylate cyclase system
- Phosphoinositol cycle
9
Q
How does magnesium effect the phosphoinositol cycle?
A
- receptor interfaces with guanosine nucleotide-binding protein (G-protein) to attach to Phospholipase C enzyme
- Phospholipase C in turn hydrolases PIP2 to generate diacylglycerol and IP3 (Intracellular signaling molecule)
- Mg2+ provides phospholipid substrate for PIP2 reaction
- De-phosphorylation (ER effect), inverse relationship between the presence of Mg2+ and deactivation of IP3 (Turns signalling off)
- Mg-ATP also drives Protein Kinase C step for further functional effects
- **Impacts muscle regulation
Don’t want IP3 to linger. Need to turn it off right after release, if you don’t have magnesium you can’t turn it off and you will have greater concentrations of calcium above what the homeostasis level is. Magnesium and calcium concentrations inverse of one another
10
Q
How does magnesium impact ion channels?
A
- Mg important role in many ion channels
- Mg necessary for the active transport of potassium OUT of cells by the well known Na/K/ATPase pump (but also passively by K+ channels
- ATP synthase also dependent on Mg2+ activity
- Direct effect on the conformation of potassium channels (more common in the myocardial tissue)
- Mg sensitive ion channels - conformational shape changes when magnesium is attached or unattached
11
Q
During different stages of an action potential what channels are open? How does magnesium impact these channels? How would depletion of magnesium then effect them?
A
- During depolarization there is an influx of sodium into the cytosol and no effect by magnesium
- As the cell slightly repolarizes then plateus Potassium leaves and calcium enters the cytosol. Magnesium inhibits and inactivates the calcium channel. Depletion of Mg would cause prolonged calcium influx and thus have prolonged depolarization
- During stage 3 where there is major depolarization, potassium goes out into cytosol. Mg inhibits this action
- During basal levels, potassium is leaving the cell but NaKATPase works to pump it back in and sodium to be pumped out. Mg acts to block outflow of K and is a cofactor for ATPase. Depletion would cause reduced activity of ATPase and intracellular K loss (because there is nothing blocking outflow). This would utimately cause retarded depolarization and a depolarized RMP
12
Q
What are the dietary sources of magnesium?
A
- Uniquitous in foods
- Moderate/severe depletion is rare (e.g. dietary restriction or disorder)
- High (Rich) dietary sources - legumes, grean leafy vegetables (anything with chlorophyll as magnesium likes to bind), nuts, ‘unpolished’ grains
- Moderate dietary sources - meats, fruits, dairy products (beverages, chocolate)
- Note: Mg in water - increases “hardness” = More Mg salts (softening can decrease Mg content)
13
Q
What is the basis for recommended intakes of Mg for breastfed infants, children, adults, pregnancy?
A
- Breastfed infants - AI based on breast milk and solif foods
- Children - have extrapolated results from balance studies in older children (EAR’s set that are based on changes in body wt and ht)
- Adults - RDA’s set at EAR + 20%. Men higher than women because of larger size
- Pregnancy - higher because of increased wt gain
14
Q
What has more Mg, formula or breast milk?
A
- Cow’s milk and soy-based have higher Mg than human milk, no evidence that formula needs to have more Mg, but manufacturers provide higher Mg in case there is a problem with bioavailability
15
Q
What are the magnesium RDAs across the life cycle?
A
16
Q
In general, how is magnesium absorbed?
A
- Absorption is inverse to amount ingested
- Normally - 30-50% is absorbed
- Absorbed alon entire intestine - but mostly in ileum and lower jejunum
- Passive AND active Mg transport systems - this would account for increased absorption when intake is lower
- Influenced by fiber and protein
- Tightly regulated
22
Q
If you were buying a magnesium supplement, what is the best to buy?
A
- Magnesium citrate is better absorbed than other organic magnesium supplements tested. Has the greatest bioavailability. Best for short term acute recovery
- Oxides have large amount of magnesium but not as bioavailable. May be better for short duration
- Absorption may be increased if deficient in magnesium
23
Q
How does magnesium enter the cell?
A
- Paracellular absorption involving Claudin-16/10 with calcium
- Active transcellular entry by TRPM6. Once in the cell, leaves as sodium comes in. NA/K/ATPase pumps sodium out and potassium in
26
Q
How much of Magnesium and potassium is actually excreted?
A
- Reabsorption is effective but can lose 5% during diuresis, + loss of K+
- Reabsorption mainly occurs in thick ascending limb (65-75%)
- Tubules = the rest
28
Q
What are the causes of magnesium deficiency?
A
- Mg depletion is usually a secondary disease (because reabsorption is usually very effective)
- GI tract; excessive secretion or impaired absorption
- Vomiting/diarrhea can cause decreased absorption
- Kidney dysfunction (depletion generally related to increased urinary excretion)
- Chronic electrolyte imbalances (diuretics)
- Osmotic diuresis
- Pressure diuresis
