Tryptophan, serotonin, chlamydia and porphyrins

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As a number of people use serotonin boosting meds and supplementsi, I thought this excerpt from one of the Vanderbilt patents would be of interest.

 

From United States Patent 6,884,784
Mitchell ,   et al. April 26, 2005
...Increased levels of tryptophan in  the liver inhibit the activity of phosphoenol pyruvate carboxykinase with consequent disruption of  gluconeogenesis. This accounts for the abnormal glucose tolerance seen in porphyriai. Increased plasmic  concentrations of tryptophan also enhances tryptophan transport into the brain. The concentration of  tryptophan in the brain is the rate-limiting factor for the synthesis of the neurotransmitter  5-hydroxytryptamine (5-HT, serotonin). Serotonin is synthesized by the endothelium of brain capillaries  for circulating tryptophan. Thus, increased concentrations of tryptophan in the brain would be expected  to enhance production of serotonin and its metabolic, 5-hydroxyindole-acetic acid (5HIAA). Acute  increases in serotonin turnover in the brain are followed by vascular and metabolic changes which include  decreases in glucose consumption, disturbances in EEG tracings, and decreases in the postischemic  neurological score. In addition, while serotonin increases brain perfusion on a single injection, repetitive  administration initially opens the blood-brain barrieri and subsequently induces vasoconstriction. It is  likely that any transient opening of the blood-brain barrier.by serotonin could allow circulating substrates  such as ALA and PBG, if present, to enter the central nervous system. As would be expected from the  location of scrotonin receptors and from the barrier function of the endothelium of cerebral arteries, the  constricting effect of serotonin is amplified in cerebral arteries where endothelium is damage or removed.  Damaged endothelial cells, as would be expected with chlamydial infection, would no longer have  operational catabolic processes for serotonin. This would be particularly true in the event of depleted ATP  as caused by chlamydial infection. This means that increased concentrations of serotonin will reach the  smooth muscle layer of the cerebral vessels and cause more constriction. Finally, serotonin is also stored in  blood platelets. Because blood platelets do not adhere and aggregate under normal conditions, they do not  release serotonin when the vessel lumen is intact. However, if the vessel lumen is altered by chlamydial  infection, platelet deposition and release of serotonin can occur.  Another adverse effect of increased serotonin levels due to porphyria is seen with nervous tissues.  Sympathetic nerve endings store serotonin taken up from the circulation. These serotonergic neurons  form plexuses around brain vessels where they are likely to liberate their serotonin contents when  subjected to cellular lysis from any cause including ischemia, free-radical ionizing damage to cell  membranes, and/or chlamydial infection.  In rats, elevated circulating tryptophan has been shown to produce structural alteration of brain astrocytes,  oligodendroglia, and neurons, as well as degeneration of Purkinje cells and wasting of axons. Similar  neurohistological alterations have been reported in patients with acute porphyria. Elevated tryptophan  levels in plasma and brain have been associated with human encepholopathy. Finally, serotonin is also  recognized as an active neurotransmitter in the gastrointestinal tract. The pharmacologic effects of  serotonin in the central nervous system and gastrointestinal tract resemble the neurological manifestations  of acute porphyric attacks. In fact, administration of either tryptophan or serotonin to humans have been  reported to cause severe abdominal pain, psychomotor disturbances, nausea, and dysuria; all of which are  symptoms of acute porphyria.  h consequent disruption of  gluconeogenesis. This accounts for the abnormal glucose tolerance seen in porphyria. Increased plasmic  concentrations of tryptophan also enhances tryptophan transport into the brain. The concentration of  tryptophan in the brain is the rate-limiting factor for the synthesis of the neurotransmitter  5-hydroxytryptamine (5-HT, serotonin). Serotonin is synthesized by the endothelium of brain capillaries  for circulating tryptophan. Thus, increased concentrations of tryptophan in the brain would be expected  to enhance production of serotonin and its metabolic, 5-hydroxyindole-acetic acid (5HIAA). Acute  increases in serotonin turnover in the brain are followed by vascular and metabolic changes which include  decreases in glucose consumption, disturbances in EEG tracings, and decreases in the postischemic  neurological score. In addition, while serotonin increases brain perfusion on a single injection, repetitive  administration initially opens the blood-brain barrier and subsequently induces vasoconstriction. It is  likely that any transient opening of the blood-brain barrier.by serotonin could allow circulating substrates  such as ALA and PBG, if present, to enter the central nervous system. As would be expected from the  location of scrotonin receptors and from the barrier function of the endothelium of cerebral arteries, the  constricting effect of serotonin is amplified in cerebral arteries where endothelium is damage or removed.  Damaged endothelial cells, as would be expected with chlamydial infection, would no longer have  operational catabolic processes for serotonin. This would be particularly true in the event of depleted ATP  as caused by chlamydial infection. This means that increased concentrations of serotonin will reach the  smooth muscle layer of the cerebral vessels and cause more constriction. Finally, serotonin is also stored in  blood platelets. Because blood platelets do not adhere and aggregate under normal conditions, they do not  release serotonin when the vessel lumen is intact. However, if the vessel lumen is altered by chlamydial  infection, platelet deposition and release of serotonin can occur. 

Another adverse effect of increased serotonin levels due to porphyria is seen with nervous tissues.  Sympathetic nerve endings store serotonin taken up from the circulation. These serotonergic neurons  form plexuses around brain vessels where they are likely to liberate their serotonin contents when  subjected to cellular lysis from any cause including ischemia, free-radical ionizing damage to cell  membranes, and/or chlamydial infection. 

In rats, elevated circulating tryptophan has been shown to produce structural alteration of brain astrocytes,  oligodendroglia, and neurons, as well as degeneration of Purkinje cells and wasting of axons. Similar  neurohistological alterations have been reported in patients with acute porphyria. Elevated tryptophan  levels in plasma and brain have been associated with human encepholopathy. Finally, serotonin is also  recognized as an active neurotransmitter in the gastrointestinal tract. The pharmacologic effects of  serotonin in the central nervous system and gastrointestinal tract resemble the neurological manifestations  of acute porphyric attacks. In fact, administration of either tryptophan or serotonin to humans have been  reported to cause severe abdominal pain, psychomotor disturbances, nausea, and dysuria; all of which are  symptoms of acute porphyria...  
 

Comments

As would be expected from the  location of serotonin receptors and from the barrier function of the endothelium of cerebral arteries, the  constricting effect of serotonin is amplified in cerebral arteries where endothelium is damage or removed.  Damaged endothelial cells, as would be expected with chlamydial infection, would no longer have operational catabolic processes for serotonin. This would be particularly true in the event of depleted ATP  as caused by chlamydial infection. This means that increased concentrations of serotonin will reach the  smooth muscle layer of the cerebral vessels and cause more constriction.

That might explain why Dianna's migraines went away when she did a CAPi<

Ron

On CAPi for CFSi starting 01/06 (NE Ohio, USA)

Began rifampin trial 1/14/09

Currently: on intermittent

So, are you saying that 5-HTP is good or bad?  I know it has helped me with sleep.  I also have IBSi and I am better.  I have been on ssri's for years (chronic depression) but have felt better with the 5-HTP.

FMSi/CFS 1995. tinnitus">i, ibsi, sinusitis, EBVi, NACi 2400mg, valtrex, cortef, armour, doxy, biaxin, tinii, vita c 5 - 10,000 daily 

Lynn- Give me an easy one! I was putting this info up in response to http://yarchive.net/med/5-htp.html< which Norman gave on his blog http://www.cpnhelp.org/pyruvate_ponderings_and_e< in a comment.

The reality is that people here have used both to good effect, but if you've had trouble with either this post might explain.

 

CAPi for Cpni 11/04. Dxi: 25+yrs CFSi & FMSi. Currently: 250 aithromycin mwf, doxycycline 100mg BIDi, restarted Tinii pulses; Vit D2000 units, T4 & T3, 6mg Iodoral

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