+ 1 Esters - where exactly is ester removed
I did my research and I m familiar with concept of esters and how they work and affect halflife of steroid molecule.
I know that when certain ester is added to the molecule it makes the molecule hydrophobic(not soluable in water, only in oil).
Once the oil is injected to the muscle, the ester is slowly removed by body enzymes, which makes molecule soluable in water and therefore active.
My question is where exactly does this de-esterification happen in the body and where exacty and in which form is esterified molecule stored before being active? In other words where exactly is this unactive molecule stored for the duration of ester hallife.
Following are my 2 theories. Could someone please confirm it or shed some light on this.
A) Is it in the injected muscle? I assume oil is probably absorbed immediately and only esterified molecule crystals will stay in the injected muscle. Enzymes then act on crystals, removing ester, making molecule soluable in water and then released into bloodflow.
or
B) injected oil is absorbed along with esterified molecule and unactive esterified molecule is flowing in the bloodflow, waiting for enzymes to kick in, removing ester and making molecule soluable in blood and active. But that means lot of unactive molecules in the bloodflow for the length of halflife. And how could unactive esterified molecules flow in the blood, when not yet soluable in water.
What are your thoughts?
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AnonGreat post and great information, much appreciated
AnonEsterases are enzymes that remove esters. They are found in all tissues in the body. Their principle purpose is to de-esterify acetylcholine to make it inactive.
Acetylcholine is the neurotransmitter found in the neuromuscular junction - the connection between nerve and muscle - acetylcholine is released by the nerve and causes the muscle to contract. Acetylcholinesterase de-esterifies the acetylcholine to stop it causing muscular contractions.
Acetylcholine can leak out of the neuromuscular junction and into blood where it can travel to other tissues. Esterases in blood de-esterify the acetylcholine so you don't get contractions happening in muscles at random. These esterases will also de-esterify steroids.
Insect sprays are nerve agents that render acetylcholinesterase inactive. Picture the fly: it buzzes around uncontrollably, contracting continuously in an uncoordinated fashion. Then it runs out of energy and dies from flaccid paralysis.
Steroids, esterified and un-esterified, are both practically insoluble in water. Likewise in blood. When they diffuse out of muscle and into blood they travel bound tightly to proteins in blood and not in solution. Esterases will act on steroids in muscle tissue and in blood. Steroids will unbind from the proteins to which they are bound and diffuse into tissue from blood.
Shorter esters are removed more readily than longer esters, hence the difference in half-lives.
HTH
Dr B
Great answer bro. Thank you.
Does that mean that esterified steroid can travel in blood bound to protein for days or weeks - depending on ester, till it s activated, right?
What does "bound to protein" exactly mean? Is that the reason why it is not cleared up by liver? I cannot imagine that some foreign substance will stay in body that long and not being clear up by some protection mechanism.
AnonYes, it can stay bound for a long time. While it's bound to the soluble proteins in blood it can pass through the liver without entering the liver cells where it would be metabolised. Some does unbind from the protein and diffuse into liver cells. The same goes for the kidneys. While bound the steroid is not filtered out of blood and into urine. If unbound and free in the water component of blood as it passes through the kidneys it can be filtered into urine and excreted.
Steroids that are metabolised in the liver are usually conjugated with a water soluble moiety (chemical) like glucuronic acid (similar to a sugar) or sulphate. The steroid is then much much more water soluble and will stay dissolved in the water component of blood, not bound to a protein. It can then be freely filtered by the kidneys and excreted. Often steroid metabolites are excreted into bile by liver cells. The bile travels into your small intestine and you subsequently excrete the steroid by shitting it out. Isn't science fascinating?
The concept to grasp is that the whole process is dynamic and composed of nearly countless numbers of molecules. Some stay bound, some diffuse from proteins into liver or muscle or other tissue. Some is still present as an oily depot in your glute.
Dr B
Amazing, your knowledge is impressing. Thanks for the missing link. FR sent
AnonI went to bed and thought I'd add this when I got up. Hopefully people are still reading.
When you get a blood done for test levels you normally get a total test level and a free test level. The free test level is always lower than the total test level. It represents the proportion of the total test in your blood that is not bound to proteins and is free to diffuse into other tissues (like muscle, liver or kidney) or interact with things like enzymes (eg esterases) or receptors (eg androgen receptors).
Sex Hormone Binding Globulin (SHBG) is a protein synthesised by your liver specifically for binding sex hormones (eg test and estrogen) in blood. It is often in your blood results too. Androgens reduce its synthesis and estrogens increase its synthesis. When you take test your total test goes up but your free test goes up proportionately more because your SHBG goes down. When your test goes down during PCT you need to watch your estrogen because it can make your SHBG go up and push your free test even lower.
I like exemestane for estrogen control because it is a weak androgen and pushes down SHBG that in turn pushes up free test.
Dr B
this information comes particularly handy as i m in first week of my first PCT. Fortunately few weeks ago decided to run aromasin in PCT(opposed to Adex which i run oncycle) , which turns out to be good decision.
Nice post bro
Liver, then brain? Brain, then liver? Good question.