INT50291

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Context Info
Confidence 0.67
First Reported 1995
Last Reported 2008
Negated 0
Speculated 0
Reported most in Body
Documents 10
Total Number 11
Disease Relevance 8.89
Pain Relevance 0.73

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

cytosol (HMBS) small molecule metabolic process (HMBS) nucleus (HMBS)
cytoplasm (HMBS)
Anatomy Link Frequency
cardiac muscle cells 1
fibroblasts 1
HMBS (Homo sapiens)
Pain Link Frequency Relevance Heat
Peripheral nervous system 2 96.76 Very High Very High Very High
abdominal pain 4 92.92 High High
dexamethasone 3 89.68 High High
alcohol 7 88.16 High High
agonist 20 82.08 Quite High
palliative 3 73.16 Quite High
Inflammation 16 62.36 Quite High
Kinase C 1 7.40 Low Low
Bioavailability 12 5.00 Very Low Very Low Very Low
Pain 4 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Porphyria 29 100.00 Very High Very High Very High
Variegate Porphyria 6 99.20 Very High Very High Very High
Coronary Heart Disease 13 99.06 Very High Very High Very High
Left Ventricular Hypertrophy 3 98.64 Very High Very High Very High
Heart Rate Under Development 17 96.24 Very High Very High Very High
Cancer 98 94.72 High High
Epilepsy 2 94.68 High High
Stroke 3 94.44 High High
Dilated Cardiomyopathy 3 94.36 High High
Constipation 2 93.48 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
It has been reported that certain types of neoplastic cells have not only reduced ferrochelatase activity, but also enhanced porphobilinogen deaminase (PBGD) activity.3,9,26 Low ferrochelatase activity may be of lesser important to deficiencies in mitochondrial energy generation because tumour cells typically have low activities of mitochondrial cytochrome oxidase and utilise glycolysis rather than oxidative phosphorylation.17 In addition, certain malignant cells have low iron stores, a characteristic of proliferating cells, leading both to increased expression of transferrin receptors and, importantly, to decreased conversion of PpIX into haem.27,28 Porphobilinogen deaminase is considered to have the lowest activity in the haem biosynthetic pathway29,30 and the reason for its up-regulation in certain tumour cells has not yet been elucidated.9 It is generally considered to be rate-limiting in the ALA-induced synthesis of PpIX in neoplastic cells.31 Notwithstanding this, other reports have failed to find a clear relationship connection between high PBGD and/or low ferrochelatase activity and PpIX accumulation.32–34

Clinical administration of ALA

Positive_regulation (enhanced) of porphobilinogen deaminase associated with malignant neoplastic disease and cancer
1) Confidence 0.67 Published 2007 Journal Perspectives in Medicinal Chemistry Section Body Doc Link PMC2754918 Disease Relevance 0.53 Pain Relevance 0
Gene delivery increased the PBGD activity 88-200 fold in human AIP fibroblasts and synthesis of PP was increased from 21-152% of normal after ALA incubation.
Positive_regulation (increased) of PBGD in fibroblasts associated with porphyria
2) Confidence 0.40 Published 2003 Journal Mol. Cell. Biochem. Section Abstract Doc Link 12962144 Disease Relevance 0.62 Pain Relevance 0.07
These mice exhibit the typical biochemical characteristics of human AIP, notably, decreased hepatic Pbgd activity, increased delta-aminolevulinic acid synthase activity and massively increased urinary excretion of the heme precursor, delta-aminolevulinic acid after treatment with drugs such as phenobarbital.
Positive_regulation (increased) of Pbgd associated with porphyria
3) Confidence 0.25 Published 1996 Journal Nat. Genet. Section Abstract Doc Link 8563760 Disease Relevance 1.05 Pain Relevance 0.13
to control the expression of components of the UPS, like ubiquitin ligases, or via
Positive_regulation (components) of UPS
4) Confidence 0.11 Published 2008 Journal PPAR Research Section Body Doc Link PMC2423003 Disease Relevance 0.17 Pain Relevance 0.07
It has been reported that certain types of neoplastic cells have not only reduced ferrochelatase activity, but also enhanced porphobilinogen deaminase (PBGD) activity.3,9,26 Low ferrochelatase activity may be of lesser important to deficiencies in mitochondrial energy generation because tumour cells typically have low activities of mitochondrial cytochrome oxidase and utilise glycolysis rather than oxidative phosphorylation.17 In addition, certain malignant cells have low iron stores, a characteristic of proliferating cells, leading both to increased expression of transferrin receptors and, importantly, to decreased conversion of PpIX into haem.27,28 Porphobilinogen deaminase is considered to have the lowest activity in the haem biosynthetic pathway29,30 and the reason for its up-regulation in certain tumour cells has not yet been elucidated.9 It is generally considered to be rate-limiting in the ALA-induced synthesis of PpIX in neoplastic cells.31 Notwithstanding this, other reports have failed to find a clear relationship connection between high PBGD and/or low ferrochelatase activity and PpIX accumulation.32–34

Clinical administration of ALA

Positive_regulation (enhanced) of PBGD associated with malignant neoplastic disease and cancer
5) Confidence 0.06 Published 2007 Journal Perspectives in Medicinal Chemistry Section Body Doc Link PMC2754918 Disease Relevance 0.53 Pain Relevance 0
We hypothesize that baseline presence of sub clinical cardiomyopathy, characterized by an adaptive, cytoprotective activation of the UPS, could have predisposed this patient for a cardiac side effect induced by systemic proteasome inhibition.
Positive_regulation (activation) of UPS associated with coronary heart disease
6) Confidence 0.05 Published 2006 Journal BMC Cancer Section Body Doc Link PMC1475607 Disease Relevance 0.75 Pain Relevance 0
Activation of the UPS, leading to an altered protein expression in cardiac muscle cells, has been proposed to be an adaptive mechanism for maintaining a normal stroke volume [15].
Positive_regulation (Activation) of UPS in cardiac muscle cells associated with stroke
7) Confidence 0.05 Published 2006 Journal BMC Cancer Section Body Doc Link PMC1475607 Disease Relevance 0.94 Pain Relevance 0.04
There is evidence from literature that activation of the ubiquitin-proteasome system (UPS) occurs in chronic conditions of left ventricular hypertrophy and (dilated) cardiomyopathy.
Positive_regulation (activation) of UPS associated with left ventricular hypertrophy and coronary heart disease
8) Confidence 0.05 Published 2006 Journal BMC Cancer Section Body Doc Link PMC1475607 Disease Relevance 0.85 Pain Relevance 0.04
During acute attacks, urinary ALA (delta-aminole-vulinic acid) and PBG (porphobilinogen) are elevated just as in AIP and VP, however, a marked elevation of faecal COPRO (coproporphyrin) is diagnostic of HCP.
Positive_regulation (elevated) of PBG associated with porphyria and variegate porphyria
9) Confidence 0.04 Published 1995 Journal Nippon Rinsho Section Abstract Doc Link 7616659 Disease Relevance 1.32 Pain Relevance 0.14
During acute attacks, urinary ALA (delta-aminole-vulinic acid) and PBG (porphobilinogen) are elevated just as in AIP and VP, however, a marked elevation of faecal COPRO (coproporphyrin) is diagnostic of HCP.
Positive_regulation (elevated) of porphobilinogen associated with porphyria and variegate porphyria
10) Confidence 0.04 Published 1995 Journal Nippon Rinsho Section Abstract Doc Link 7616659 Disease Relevance 1.32 Pain Relevance 0.14
Urinary excretion of porphobilinogen (PBG) and uroporphyrin was only slightly increased.
Positive_regulation (increased) of porphobilinogen associated with porphyria
11) Confidence 0.00 Published 2004 Journal J. Inherit. Metab. Dis. Section Abstract Doc Link 15303011 Disease Relevance 0.82 Pain Relevance 0.09

General Comments

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