SUPPLEMENTAL FIGURE LEGENDS
Supplemental Figure 1: Conservation of the TPI amino acid
sequence. ClustalW alignment (Megalign, DNAstar) reveals the
highly conserved nature of the TPI protein between invertebrates and
vertebrates including humans. Red boxes indicate identity to
consensus, orange boxes indicates a conservative substitution.
Known human mutations are indicated with a bullet above the
affected amino acid, as follows: black are substitutions, orange are
temperature-sensitive substitutions, and purple result in truncated
proteins. The Drosophila sgk1 mutation is indicated with a blue bullet.
Yellow bars indicate described dimer interaction sites (SCHNEIDER
2000). Species abbreviations are: A.g. Anopheles gambiae,
XP_321467); D.m. (Drosophila melanogaster, NP_788765, TpiF
variant); M.m. (Mus musculus, AAH46761); R.n. (Rattus norvegicus,
AAR23524); G.g. (Gallus gallus, NP_990782), X.l. (Xenopus laevis,
AAH46864); and H.s. (Homo sapiens, AAH07086). Human mutation
data obtained from the following: initiation codon (TPI Paris)
(VALENTIN et al. 2000), frameshift in codon 29 (TPI Alfortville)
(VALENTIN et al. 2000), Cys41Tyr (ARYA et al. 1997), Gly72Ala
(WATANABE et al. 1996), Glu104Asp (DAAR et al. 1986),
Glu145Termination (HOLLAN et al. 1997), Val154Met (WATANABE et al.
1996), Ile170Val (ARYA et al. 1997), Arg190Termination (DAAR and
MAQUAT 1988), Val231Met (SCHNEIDER 2000), Phe240Lys (CHANG et
al. 1993).
Supplemental Figure 2: Overview of glycolysis. The known
biochemical pathway is thought to yield two each ATP, NADH and
pyruvate per molecule of glucose. Loss of TPI function is predicted to
yield one each NADH, pyruvate and dihydroxyacetone phosphate
(DHAP) per molecule of glucose. Figure adapted from (GARRETT
1995).
SUPPLEMENTAL REFERENCES
ARYA, R., M. R. LALLOZ, A. J. BELLINGHAM and D. M. LAYTON, 1997 Evidence for
founder effect of the Glu104Asp substitution and identification of new
mutations in triosephosphate isomerase deficiency. Hum Mutat 10: 290-294.
CHANG, M. L., P. J. ARTYMIUK, X. W U, S. HOLLAN, A. LAMMI et al., 1993 Human
triosephosphate isomerase deficiency resulting from mutation of Phe-240.
Am J Hum Genet 52: 1260-1269.
DAAR, I. O., P. J. ARTYMIUK, D. C. PHILLIPS and L. E. MAQUAT, 1986 Human triosephosphate isomerase deficiency: a single amino acid substitution results in a
thermolabile enzyme. Proc Natl Acad Sci U S A 83: 7903-7907.
DAAR, I. O., and L. E. MAQUAT, 1988 Premature translation termination mediates
triosephosphate isomerase mRNA degradation. Mol Cell Biol 8: 802-813.
GARRETT, R., GRISHAM, CM, 1995 Biochemistry. Saunders College Publishing,
New York.
HOLLAN, S., M. MAGOCSI, E. FODOR, M. HORANYI, V. HARSANYI et al., 1997 Search
for the pathogenesis of the differing phenotype in two compound
heterozygote Hungarian brothers with the same genotypic triosephosphate
isomerase deficiency. Proc Natl Acad Sci U S A 94: 10362-10366.
SCHNEIDER, A. S., 2000 Triosephosphate isomerase deficiency: historical
perspectives and molecular aspects. Baillieres Best Pract Res Clin Haematol
13: 119-140.
VALENTIN, C., S. PISSARD, J. MARTIN, D. HERON, P. LABRUNE et al., 2000 Triose
phosphate isomerase deficiency in 3 French families: two novel null alleles, a
frameshift mutation (TPI Alfortville) and an alteration in the initiation codon
(TPI Paris). Blood 96: 1130-1135.
WATANABE, M., B. C. ZINGG and H. W. MOHRENWEISER, 1996 Molecular analysis of
a series of alleles in humans with reduced activity at the triosephosphate
isomerase locus. Am J Hum Genet 58: 308-316.