Chemistry Reference
In-Depth Information
are proteolytically removed before the protein assumes its mature form. The
19 amino acid pre-sequence is first removed in the ER by a signal peptidase,
yielding pro-LPH molecules, which become N-glycosylated and pair up to
form homodimers (Grunberg and Sterchi, 1995). This dimerisation is essen-
tial for the acquisition of transport competence and full enzymic activity of
LPH (Naim and Naim, 1996). Further (O-linked) glycosylation occurs once
the pro-LPH homodimer has been translocated to the Golgi apparatus, which
is also the predominant site of proteolytic cleavage of the pro-sequence (Naim
et al., 1987). The pro-sequence has been shown to play a vital role in the
maturation of LPH, being involved in folding, targeting and dimerisation of
the molecule (Panzer et al., 1998).
Residues from Ala 867 onwards comprise the 160 kDa glycoproteins
found anchored to the brush border of the jejunum as mature LPH homo-
dimers (Mantei et al., 1988). LPH is an amphiphilic molecule, consisting of a
short cytoplasmic domain followed by a membrane-spanning hydrophobic
domain (residues 1883-1901) at its C-terminus, orientating the molecule such
that the bulky, hydrophilic N-terminal projects into the lumen (Skovbjerg
et al., 1981; Wacker et al., 1992). It is within this N-terminal portion that both
catalytic activities reside, and it has been demonstrated that the active site for
phlorizin hydrolysis is distinct from that for lactose (Leese and Semenza,
1973; Columbo et al., 1973; Skovbjerg et al., 1981). The active sites are
situated within the homologous domains III (Glu1271) and IV (Glu1747),
respectively (Arribas et al., 2000).
The 'phlorizin hydrolase site' is situated closest to the brush border and
preferentially catalyses the hydrolysis of
-glycosides with large, hydrophobic
aglycones (galactosyl and glucosyl
-ceramides, phlorizin and other aryl- or
alkyl-
-glycosides). The 'lactase' catalytic site has been shown to have a
preference for
-glycosides with hydrophilic aglycones (e.g. lactose, cello-
biose and some
-1,4-linked small glucose oligomers) (Leese and Semenza,
1973; Columbo et al., 1973; Skovbjerg et al., 1981). LPH is also capable of
hydrolysing various flavonol and isoflavone glucosides (Day et al., 2000), but
it is not currently known which active site is used.
6.3.
Symptoms of Lactose Intolerance
The symptoms of lactose intolerance due to lactose malabsorption, and
caused when milk is consumed by a lactase non-persistent person, vary
greatly from person to person, but if they are evident, they usually manifest
themselves within 1-2 h of ingestion.
Undigested lactose passing through the small intestine into the colon
has two physiological effects. First, an osmotic gradient is set up across the
