Calcium and Phosphorous

Calcium and phosphate, two elements that you might think of as packaged up in hydroxyapatite in bone. But they can do much more than that!

Understand the many roles of of calcium through the examples given

Aside from being a crucial component of your bones, calcium has many other roles. Here are just a few examples:

Co-factor in smooth muscle contraction

See earlier post: Physiology of Smooth Muscle

Neuron firing

Calcium is involved in the process of neuron firing. It enters the postsynaptic neuron following binding of glutamate to an NMDA receptor. Once inside the neuron, calcium binds to our good friend calmodulin. Ca²⁺-calmodulin can then activate NOS (nitric oxide synthase), which produces NO. NO, being a small molecule, can easily diffuse back across the synapse to the presynaptic terminal o the previous neuron.

When NO enters the presynaptic neuron, it can activate soluble guanylate cyclase (sGC). Guanylate cyclase, as you should hopefully know by now, can produce cGMP from GTP. cGMP can activate protein kinase G (PKG), which reinforces the vesicle transport of glutamate.

As for glutamate? Well, it either gets converted to glutamine or is taken back up into the presynaptic neuron by glutamate transporters.

TCA cycle

Calcium can enter the mitochondria through a uniporter. Once inside, it can help to regulate the TCA cycle. Specifically, it can help with the regulation of isocitrate dehydrogenase, α-ketoglutarate dehydrogenase and pyruvate dehydrogenase (okay, pyruvate dehydrogenase isn't technically part of the TCA cycle, but whatever).

Apoptosis

Apoptosis is also a complicated process requiring several steps, which is a good thing because you wouldn't want your cells killing themselves randomly. Firstly, either Ca²⁺ or binding of BID (BH3-interacting domain death agonist) on the mitochondria can cause the permeability of the mitochondria to change. This causes release of cytochrome C from the mitochondria. Cytochrome C can then go on to bind to IP₃ receptors in the endoplasmic reticulum, allowing for release of even more calcium from the ER (thus making the mitochondria release even more Cyt C- a vicious cycle!). Ultimately, this leads to the formation of apoptosomes which are vesicles that can release caspases. Caspases are enzymes involved in cell death.

Phosphate for energy, signalling and messaging in biology

Phosphorous normally isn't found in the body just on its own- it is normally found as phosphate, which is basically phosphorous attached to four oxygen atoms. Phosphate can be found dissolved in solution, or bound to biological molecules.

Nucleotides

Phosphorous is part of the backbone of DNA and RNA. Its negative charge helps to repel free radicals and thus protect nucleic acids from their damaging effects.

Co-factors

Phosphorous is involved in several electron carrier molecules. These include NAD and FAD, which you should already know, as well as FMN (flavin mononucleotide). All of these are based off B-vitamins, so eat yo' B-vitamins, kids.

ATP

ATP (adenosine triphosphate), as you should know, is basically the "energy currency" of the cell. It can release energy when one of more of its phosphates are ripped off it. ATP is also used in phosphorylation reactions- after all, those phosphates have to come from somewhere! Another use of ATP is that it can serve as a co-factor in other processes, such as carboxylation.

ATP usually does not float around by itself. It is usually complexed with Mg²⁺, which helps to shield the negative charge and influence the conformation of the phosphate groups.

GTP

GTP can also act as an energy source, just like ATP. GTP is also important in cell signalling. Remember G-proteins? G-proteins are proteins that can bind both GTP and GDP, but are usually active only when GTP is bound. GTP can be converted back into GDP by a GTPase activating protein (GAP). GDP can be removed and replaced with a fresh GTP by the use of guanine nucleotide exchange factors (GEF). Hence, G-proteins are part of the many complex signalling pathways used by the cell.

An example of G-protein signalling is found in the Ras pathway. Ras is a G-protein that can be activated by a guanine exchange factor called Sos1, which in turn is activated by tyrosine kinase. When Ras is activated, it can proceed down several different pathways, all of which aid in survival and proliferation of the cell.

Another example of G-protein signalling is in the phosphatidylinositol pathways activated by G-protein coupled receptors. You can find examples on this here and here.

Biomarkers

There are many other molecules that use phosphate. Some of these molecules, such as phosphocholine and phosphocreatine, can also be used as biomarkers for cancer. Phosphocholine is an intermediate in the synthesis of phosphatidylcholine, whereas phosphocreatine is another energy store in the muscle and brain.

Know the daily requirements for calcium and phosphate and disorders related to over and under supply

Daily requirements for calcium:

• Young children: 500-700 mg/day
• Teenagers: 1300 mg/day
• Adults: 1000 mg/day. Older adults may need more (~1300 mg/day).

Daily requirements for phosphorous (pretty similar to calcium):

• Young children: 500 mg/day
• Teenagers: 1300 mg/day
• Adults: 1000 mg/day

Calcium can be found in spices, whey, cereals and milk products. Phosphorous can be found in pretty much everything, but the slide lists spices, seeds, whey and egg yolk.

Calcium deficiency is a much greater concern than phosphorous concern as calcium loss is not well controlled. Furthermore, there is a laundry list of conditions that can negatively affect calcium absorption, such as low vitamin D levels, too much caffeine and alcohol, certain medical conditions and certain medicines. One such disorder related to low calcium is osteoporosis, which leaves its sufferers at greater risk of fractures. Supplementation might be considered if calcium levels are low. Supplements include calcium carbonate, calcium citrate and hydroxyapatite, which might come packaged with vitamin D to aid in absorption.

Phosphorous deficiency is very rare. As I said above, phosphorous is found in pretty much everything. Deficiencies are possible, however, and mainly occur in chronic alcoholics (who have impaired absorption and increased excretion) and in premature babies (due to their high growth rate).