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June 21, 2009 at 11:04 pm #1075DrMariano2Participant
Here is a steroid biosynthesis chart that I created which helps clear up questions about the synthesis of various steroid signals. For the longest time, I wanted to create a clear chart since the existing ones are not very clear or easy to memorize. Even Jonathan Wright, M.D., who invented estrogen replacement therapy with Tri-Est more than 30 years ago, to this day, can’t remember his steroid tree well despite having a steel-trap memory, where he can remember things he read word-for-word 10 years ago.
What is so interesting is that so many of the enzymes are cytochrome P450 enzymes – which mean they are iron dependent. Thus if one is low in ferritin (a measure of iron available to cells, as opposed to iron already in hemoglobin or myoglobin), one may be impaired in steroid hormone biosynthesis.
Additionally, the 2-hydroxy and 4-hydroxy estrogens are degraded by catechol-O-methyl transferase, the same enzyme that degrades the catecholamines, such as norepinephrine. Thus under stress, more norepinephrine is made and competes with the estrogens for degradation, prolonging the duration of action of the more carcinogenic 4-hydroxy estrogens.
I’ll update this as we go forward. Post a comment if you would like. Looks like I’ll have to increase the allowable sizes on attachments.
Cheers,
Dr. M
June 22, 2009 at 1:08 pm #2135chaosMemberDownloaded and saved to the desktop.
I remember reading somewhere that pregnenolone is further 5AR’d to something else. Did I miss this on the chart?
If one didn’t have ferritin measured directly on a blood draw, would there be any other indicators anywhere else that it was out of range?
June 22, 2009 at 1:49 pm #2130DrMariano2Participant@chaos 224 wrote:
Downloaded and saved to the desktop.
I remember reading somewhere that pregnenolone is further 5AR’d to something else. Did I miss this on the chart?
If one didn’t have ferritin measured directly on a blood draw, would there be any other indicators anywhere else that it was out of range?
I did the most important pathways to keep things clear – to allow clinicians to be clear headed. The actual pathways are much much more wildly complicated. For example, I left out all of the elimination pathways because there are a ton of them. There are also many side-tracks, etc. that are not as commonly clinically significant. There are also many intermediate structures, which aren’t as clinically useful but in some cases may be present. For example, it takes 5 steps for aromatase to transform testosterone to estradiol. The four intermediate products are not that useful to note.
I’ll probably add to the chart the progesterone metabolites created by 5-alpha-reductase since they are important in the brain. I missed them this go-round.
Here are some basic links if you want to boggle your mind:
http://www.genome.jp/kegg/pathway/map/map00140.html
http://www.genome.jp/kegg/pathway/map/map00150.html
http://www.genome.jp/dbget-bin/show_pathway?ko00100+C00187
FERRITIN: in regard to lab testing, other tests for iron won’t tell what the ferritin level is. Thus ferritin will need to be done.
June 22, 2009 at 5:34 pm #2136chaosMemberWHOA!!! Talk about a wiring diagram!
June 22, 2009 at 7:17 pm #2131DrMariano2ParticipantAnd those are just the basic ones. 🙂
The biochemistry to sustain life is extremely complex. One can get overwhelmed thinking about how much is going on simultaneously.
But to make clinical decisions we have to simplify and focus on the most likely pathways that cause problems. These will be the targets of treatment.
The wiring diagram I drew makes things a whole lot clearer.
June 23, 2009 at 2:11 pm #2134pmgamer18MemberThanks for the Chart Dr. M I needed one like this in my files I have links to others but dam if I can find them this one is in my PC file.
PhilJune 23, 2009 at 4:37 pm #2133hardasnails1973Member@pmgamer18 249 wrote:
Thanks for the Chart Dr. M I needed one like this in my files I have links to others but dam if I can find them this one is in my PC file.
PhilI am looking for the specific chart that will elaborate on this even more through deeper estrogen metabolism
June 23, 2009 at 5:41 pm #2138JanSzMember@hardasnails1973 253 wrote:
I am looking for the specific chart that will elaborate on this even more through deeper estrogen metabolism
You can get more more in depth by using this:
http://www.expasy.org/cgi-bin/show_thumbnails.pl
Good place to start is on maps
columns IJKL
lines 9 & 10http://www.expasy.org/cgi-bin/show_image?I9&right
words in blue have links
On attachment I have patched up this area so it can be quickly seen for quick view.
If you are interested in any other (combined) maps just ask.
Resolution may not be the greatest.
..
June 23, 2009 at 7:49 pm #2132DrMariano2Participant@JanSz 254 wrote:
You can get more more in depth by using this:
http://www.expasy.org/cgi-bin/show_thumbnails.pl
Good place to start is on maps
columns IJKL
lines 9 & 10http://www.expasy.org/cgi-bin/show_image?I9&right
words in blue have links
On attachment I have patched up this area so it can be quickly seen for quick view.
If you are interested in any other (combined) maps just ask.
Resolution may not be the greatest.
..
That’s a nice wall-sized pathway map. Thanks for sharing it. 🙂
June 23, 2009 at 8:22 pm #2139JanSzMember@DrMariano 257 wrote:
That’s a nice wall-sized pathway map. Thanks for sharing it. 🙂
You are welcome.
Please do not overlook the embeded links on those charts..
.June 23, 2009 at 10:23 pm #2137chaosMemberI thought it was the runway diagram for O’Hare.
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