PMID- 2768266
OWN - NLM
STAT- MEDLINE
DCOM- 19891012
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 264
IP  - 26
DP  - 1989 Sep 15
TI  - Defective lysosomal egress of free sialic acid (N-acetylneuraminic acid) in 
      fibroblasts of patients with infantile free sialic acid storage disease.
PG  - 15316-22
AB  - Egress of free NeuAc from normal lysosome-rich granular fractions was assessed at 
      NeuAc concentrations of up to 221 pmol/hexosaminidase unit, achieved by exposure 
      of growing fibroblasts to 40-125 nM N-acetylmannosamine for up to 7 days. The 
      normal velocity of NeuAc egress increased with NeuAc loading and with 
      temperature, exhibiting a Q10 of 2.4, characteristic of carrier-mediated 
      transport. Fibroblasts cultured from five patients with infantile free sialic 
      acid storage disease (ISSD) contained approximately 139 nmol of free NeuAc/mg of 
      whole cell protein, or 100 times the normal level. Differential centrifugation, 
      as well as density gradient analysis using 25% Percoll, showed that the stored 
      NeuAc cosedimented with the lysosomal enzyme beta-hexosaminidase. The velocity of 
      appearance of free NeuAc outside ISSD granular fractions was negligible, even at 
      initial loading levels of up to 3500 pmol/hexosaminidase unit. The lack of egress 
      from ISSD granular fractions was found for both endogenous and 
      N-acetylmannosamine-derived NeuAc. Fibroblasts from ISSD parents did not 
      accumulate excess free NeuAc and did not display a velocity of NeuAc egress 
      significantly different from normal. The defect in ISSD, like that in Salla 
      disease, appears to be an impairment of carrier-mediated transport of free NeuAc 
      across the lysosomal membrane. Clinical and biochemical differences between Salla 
      disease and ISSD may reflect differences in the amount of residual NeuAc 
      transport capacity.
FAU - Tietze, F
AU  - Tietze F
AD  - Laboratory of Molecular and Cell Biology, National Institute of Diabetes and 
      Digestive and Kidney Diseases, Bethesda, Maryland 20892.
FAU - Seppala, R
AU  - Seppala R
FAU - Renlund, M
AU  - Renlund M
FAU - Hopwood, J J
AU  - Hopwood JJ
FAU - Harper, G S
AU  - Harper GS
FAU - Thomas, G H
AU  - Thomas GH
FAU - Gahl, W A
AU  - Gahl WA
LA  - eng
GR  - 10981/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Sialic Acids)
RN  - GZP2782OP0 (N-Acetylneuraminic Acid)
SB  - IM
MH  - Carbohydrate Metabolism, Inborn Errors/genetics/*metabolism
MH  - Cell Fractionation/methods
MH  - Cells, Cultured
MH  - Centrifugation, Density Gradient/methods
MH  - Fibroblasts/metabolism
MH  - Genetic Carrier Screening
MH  - Humans
MH  - Infant
MH  - Kinetics
MH  - Lysosomes/*metabolism/ultrastructure
MH  - N-Acetylneuraminic Acid
MH  - Reference Values
MH  - Sialic Acids/*metabolism
EDAT- 1989/09/15 00:00
MHDA- 1989/09/15 00:01
CRDT- 1989/09/15 00:00
PHST- 1989/09/15 00:00 [pubmed]
PHST- 1989/09/15 00:01 [medline]
PHST- 1989/09/15 00:00 [entrez]
AID - S0021-9258(19)84828-7 [pii]
PST - ppublish
SO  - J Biol Chem. 1989 Sep 15;264(26):15316-22.