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Strange symptoms
I don't know if I'm being paranoid or not, but I'm just gonna put it out there anyway.
After further looking at some of my 23andme genes related to glucose metabolism, I found a SNP that might, or might not, say something. I'm sure I have many others that are significant.
But I'm thinking, maybe I should have noticed something wrong a long time ago. I have had periods of feeling weak in my arms throughout my life, and a lot more often during the past year.
PFKM - phosphofructokinase
7 homozygous SNPs, one of which is non-synonymous, i.e., a mismatch mutation that changes one amino acid in the protein:
rs2228500 Arg100Gln
I then found this paper relating it to glycogen storage disease type VII:
http://www.ncbi.nlm.nih.gov/pmc/article ... 7-0139.pdf
This describes the function of the protein and the effects a mutation that would reduce its activity in vivo would have:
Then the case related to my SNP (rs2228500), called the exon 6 mutation substituting Gln for Arg-100:
I wonder if my slightly elevated bilirubin and CK are related to this. Though my diet for 1-2 weeks before the blood test was full fat goat milk and simple sugars. Now, after two weeks on no simple sugars, lots of rice/masa and low fat, I've lost more weight and gotten worse. Maybe I'm seeing connections that aren't there...
messtafarian said:post 108826 messtafarian
I don't know if I'm being paranoid or not, but I'm just gonna put it out there anyway.
After further looking at some of my 23andme genes related to glucose metabolism, I found a SNP that might, or might not, say something. I'm sure I have many others that are significant.
But I'm thinking, maybe I should have noticed something wrong a long time ago. I have had periods of feeling weak in my arms throughout my life, and a lot more often during the past year.
PFKM - phosphofructokinase
7 homozygous SNPs, one of which is non-synonymous, i.e., a mismatch mutation that changes one amino acid in the protein:
rs2228500 Arg100Gln
I then found this paper relating it to glycogen storage disease type VII:
http://www.ncbi.nlm.nih.gov/pmc/article ... 7-0139.pdf
This describes the function of the protein and the effects a mutation that would reduce its activity in vivo would have:
A major rate-limiting step of glycolysis, phosphorylation
of fructose-6 phosphate to fructose-1,6 bisphosphate, is
catalyzed by phosphofructokinase (PFK; ATP, fructose-6-
phosphate 1-phosphotransferase; E.C.2.7.1.1 1). The mammalian
PFK is a tetrameric enzyme and is subject to allosteric
regulation
...
An inherited deficiency of PFK, glycogenosis type VII, results in a complete
block in muscle glycolysis, leading to intolerance to exercise,
cramps, myoglobinuria, and compensated hemolysis. The observed clinical symptoms reflect
the lack of PFK in muscle and partial reduction of the enzyme in erythrocytes.
Then the case related to my SNP (rs2228500), called the exon 6 mutation substituting Gln for Arg-100:
The Swiss patient, who suffered from muscle PFK deficiency
of the classic type, is a genetic compound: a G-to-A
transition in exon 6, inherited from her mother, would
predict a substitution of Gln for Arg-100, and a G-to-A
transition in exon 22, inherited from her father, would
predict a substitution of His for Arg-696.
The exon 6 mutated allele is underexpressed,
...
The reason for the lower level of transcription from this allele is not
clear. It could be due to the mutation itself and/or the
effect of the base change at the TSP. However, there might
be another mutation farther upstream that affects PFK expression
in the Swiss patient.
The disease-causing mutations are expected to occur either
at the catalytic site of the PFK molecule or at the subunit
interaction site, since the ability to form polymers is
critical for the enzyme function and the smallest active
form of PFK in vitro is a tetramer.
Arg-100 and Arg-696, the sites of mutations in exons 6 and 22 in the Swiss
patient, are not located in evolutionarily conserved regions
and are not duplicated in the protein. Furthermore, Arg-
696 in the C-terminal part lies within the stretch of amino
acids that stand out as "extra residues" when the two
halves of the human muscle kinase are aligned with the
bacterial sequence. Although these changes would predict
a minimal effect on protein structure, we think that the
mutations are pathogenic, because (i) the entire coding region,
as well as the upstream regulatory region, was sequenced,
and no other abnormalities were found; and (ii)
30 control subjects contained normal sequences in exons 6 and 22.
...
The function of human mutant PFK was studied by
complementation of the engineered yeast strains devoid of
the endogenous PFK activity.
...
The genotype-phenotype relationship in a Swiss patient
is less clear, because Arg-100 (exon 6) and Arg-696 (exon 22)
mutants expressed in yeast resulted in only modest
changes in the stability of the enzyme. These mutants produce
functional enzyme in yeast but apparently not in humans.
The difference could be attributed either to different
conformational states of the tetrameric enzyme in human
and yeast cells or to different stability of the enzyme in the
extracts for enzyme assay in both systems. It is interesting
that the patient has residual PFK activity in muscle biopsy
(9.3 mU/mg; ~8% normal), indicating that small amounts
of functional enzyme are produced in vivo as well. In several
reported cases with measurable amounts of residual
PFK, the clinical syndrome was not atypical (Rowland et
al. 1986). It is also important to emphasize that in vivo the
tissue-specific regulation of the enzyme is controlled by
a complex of mechanisms, including modulation by the
effectors, phosphorylation, and control of synthesis and
degradation, conditions that cannot be faithfully reproduced
in a surrogate yeast host.
I wonder if my slightly elevated bilirubin and CK are related to this. Though my diet for 1-2 weeks before the blood test was full fat goat milk and simple sugars. Now, after two weeks on no simple sugars, lots of rice/masa and low fat, I've lost more weight and gotten worse. Maybe I'm seeing connections that aren't there...
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