Magnesium Flashcards
Physicochemistry characteristics of magnesium
Functions as a divalent ion and is usually found bound to other ligands and molecules, chelating with anionic ligands.
* Can bind the highly charged anionic molecules
* acts primarily as a stabilizer and complexer
* large hydrated volume and is typically not flexible in its binding state, so not a buffer
Abundancy of Mg in the body
highly abundant cation - 4th in body overall after Ca, K and Na.
* 2nd within the cell.
Distribution of Mg
Mostly in the skeleton and soft tissue
* 1% is extracellular and 0.6% is actually free ion in serum
What are some general physiological functions of Mg?
- cellular energy metabolism of FAT and CHO
- structural stabilizer
- nucleic acid and protein synthesis
- Second messengar systems
- Ion channels
What are some common molecules that require Mg in their structure?
Needed for structural stabilization and function
* ADP/ATP conformation
* Enzymes in glycolysis
Mg role in ADP/ATP conformation
- structure requires Mg to stabilize the phosphate groups
- Mg allows ATP and ADP to accept or to give up a phosphate group.
Where is Mg neccessary in glycolysis?
These structures require Mg to interact with substrates
* Step 1: Glucose to G-6-P
* Step 3: F6P to FBP
* Step 7: 1,3 BPG to 3-PG
* Step 9: 2PG to PEP
* Step 10: PEP to Pyruvate
Mg role in nucleic acid and protein synthesis
Mg 2+ binds specifically to phosphate groups on Nucleic Acids which allows Mg2+ to be very effective as shielding agents for NA (compared to mono-valent ions)
* Mg 2+ ion has an influence on the DNA double helix equivalent to that of 100-1000 Na+ ions.
* Most NA or nucleotides require Mg 2+ ion for activity and for structural stabilization
What second messenger systems is Mg necessary for?
- Adenylate cyclase system
- phosphoinositol cycle
Mg in the adenylate cyclase system
In this system a receptor interfaces with guanine nucleotide-binding protein (G-protein) and there is a reaction cascade to induce a response
* Activation of G-protein sub-units require the presence of both GTP and Mg 2+ and Mg is also thought to bind directly onto G-protein to further enhance activity of the interaction
* Mg 2+ also required for ATP to drive cyclic AMP link and to provide energy for the Kinase A step.
Mg in the phosphoinositol cycle
In this cycle a receptor interfaces with guanine G- protein to attach to Phospholipase C enzyme
which in turn hydrolyses PIP2 to generate diacylglycerol and IP3 which IP3 releases Ca2+ from ERA
* Mg2+ provides phospholipid substrate (ATP) for PIP2 reaction
* Mg2+ dephosphorylates IP3 to deactivate it
* Mg-ATP also drives Protein Kinase C step for further functional effects
Mg2+ function in ion channels
Mg2+ has a direct effect on the conformation of potassium channels by inserting in the tertiary structure (more common in the myocardial tissue)
* Mg 2+ necessary for the active transport of potassium OUT of cells by the Na+K+ ATPase pump
* also passively by K+ channels
* ATP synthase also dependent on Mg 2+ for activity
Cardiac excitation and potential effects of Mg depletion
- inhibits influx of Ca2+ so in depletion there is prolonged influx and depolarization
- Blocks outflow of K+ so with depletion K+ is lost from cytsol leading to retarded repolarization and depolarized resting membrane potential
- Mg is a co-factor for ATP so there is reduced activity which also leads to a depolarized resting membrane potential
How prevalent is Mg in food?
Mg2+ is fairly ubiquitous in foods
What are some rich dietary sources of Mg?
- legumes and tofu
- green leafy veg’s (anything with chlorophyll)
- nuts
- ‘unpolished’ (whole) grains
What are some moderate dietary sources of Mg?
- meats
- fruits
- dairy products
How is Mg present in water?
More Mg salts are seen in hard water which it contributes too
* Mg content decreased in softened water
Units for Mg DRIs
Mg/d
Mg DRIs
Basis for Mg infant DRIs
30µg/d for 0-6m and 75µ/d for 6-12m
* AI based on breast milk and solid foods
* Formula Fed infants - 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
Basis for Mg children DRI
have extrapolated results from balance studies in older children (EAR’s set that are based on changes in body wt and ht)
* increases with age
Basis for Mg DRIs for adults
RDA’s set at EAR + 20%.
* Men higher than women because of larger size
Basis for MG DRIs for pregnancy and lactating
- pregnancy: higher because of increased weight gain
- lactating: same as adult female
How can Mg be acutely lost?
Through sweat during exercise with loss of electrolytes
* Should drink complex electrolyte mix
What is the absorption capability of Mg?
normally 30-50% bioavailability but absorption is inverse to the amount ingested
Where is Mg absorbed?
Absorbed along entire intestine - but mostly in ileum and lower jejunum - via passive and active transport systems
Influence of protein on Mg absorption
Mg absorption is lower when protein intake is very low, but not clear.
Influence of fibre on Mg absorption
high levels of fibre may decrease absorption - but generally these foods are high in Mg
* phytate and other proteins may also confound absorption by binding Mg and competition for transportation
What endogenous factors improve Mg absorption?
Low Mg2+ status
What endogenous factors impair Mg absorption?
- Increasing age
- Balanced Mg2+ status
- Intestinal dysfunction (eg in CD, IBD or SBS)
What exogenous factors might increase Mg absorption?
- Low - or indigestible carbohydrates (ie. oligosaccharides, inulin, mannitol and lactulose)
- High solubility of Mg2+
- Solubilized Mg2+ (eg. effervescent tablets)
- MCT (SFA) (?)
- Proteins (?)
- Casein phosphopeptides (?)
What exogenous factors might decrease Mg absorption?
- High single Mg2+ intake dose
- Partly fermentable fibres (hemicellulose)
- Non-fermentable fibres (cellulose and lignin)
- LCT (?)
- Phytate
- Oxylate
- Pharmocological doses of calcium, phosphorus, iron, copper, manganese and zinc
- Slow-release formulations (?)
What is the bioavailability of different types of Mg that can go into supplements?
Magnesium Citrate is better absorbed than other organic magnesium supplements tested. Also, your absorption may also be increased if you are deficient in magnesium.
What forms of Mg supplements are better for chronic vs. acute supplementation?
- Mg oxide has the most % of Mg in supplement but it is not very bioavailable therefore probably better for chronic supplementation
- Mg citrate has little % of Mg in supplement but highly bioavailable so probably better choice for acute supplementation
Types of Mg transporters
- Paracellular active channels - Claudin-16/19
- Passive channels - TRPM6
- Specific channels
- Mg-Na pump on basallateral membrane
Principle organ of magnesium excretion
The Kidney
How much Mg is typically reabsorbed?
70% of plasma Mg is filtered as free Mg, therefore most Mg can be reabsorbed
Where is Mg reabsorbed?
most Mg reabsorbed in proximal and thick ascending tubules (accounts for approx 75-90% of reabsorption)
* reabsorption likely to involve transport mechanism in some but not all parts of the kidney
What is required for Mg reabsorption?
- requires the use of K+ ions for re-absorption
What drives Mg reabsorption?
Driven by Na, H2O and conc of Mg in filtrate
What is the effect of Mg reabsorption on K+
Trying to reabsorb lots of Mg uses up K+ and may cause K+ deficiency
Causes of Mg deficiency
Deficiency is usually a secondary disease since re-absorption is usually very effective
* GI tract; excessive secretion or impaired absorption
* Vomiting/Diarrhea can cause decreased absorption
* kidney dysfunction with increased excretion
* chronic electrolyte imbalance
* osmotic diuresis
* pressure diuresis
What is diuresis?
an increased flow of urine produced as the result of increased fluid intake, absence of hormonal activity, or the taking of certain drugs that reduce sodium and water reabsorption from the tubules.
What is osmotic diuresis?
excess urinary excretion due to poorly re- absorbable molecules in tubules
* eg glucose during diabetes as it is trying to get rid of excess glucose
What is pressure diuresis?
a compensatory response by the kidneys to maintain blood pressure when high
* an increased flow of urine produced as the result of increased fluid intake, absence of hormonal activity, or the taking of certain drugs that reduce sodium and water reabsorption from the tubules.
What are examples where there might might chronic electrolyte imbalance?
- diuretics
- excess exercise
- medications
How would Mg deficiency from renal loss effect CVD risk and heart function?
- prolonged influx of Ca2+ into cardiac muscle cells resulting in prolonged depolarization
- More K+ is lost from cytsol leading to retarded repolarization and depolarized resting membrane potential
- Reduced activity of ATP-ase whick also leads to a depolarized resting membrane potential
What are the major manifestations of Mg deficiency?
Mg is important for many things so often see a compound + cascade effect
* biochemical
* neuromuscular and psychiatric
* Cardiovascular
* gastrointestinal
Manifestations of Mg deficency for gastrointestinal
- nausea
- vomitting
Symptoms of neuromuscular and psychiatric Mg deficiency
Seizures, vertigo, muscular weakness, tremor, headaches
Manifestations in cardiovascular with Mg deficiency
- ECG abnormalities
- Cardiac dysrhythmias
- smooth muscle irregularities (vascular)
Biochemical manifestations with Mg deficiency
- hypokalemia
- hypocalcemia
- Impaired PTH secretion
- renal and skeletal resistance to PTH
How does Mg deficiency result in hypokalemica
Kidney tries to reabsorb more Mg which depletes K+
How does Mg result in hypocalcemia?
- Ca2+ is dysfunctional in cell
- low absorption of Ca2+ during Mg2+ deficiency
- PTH metabolism also affected.
How does Mg deficiency impair PTH secretion?
reduces Ca2+ absorption
How does Mg deficiency causes renal and skeletal resistance to PTH?
reducing action of VitD and PTH due to reduced activity of adenylate cyclase system
