384
J . T . D I N G L E A N D M . W E B B
of acid-hydrolases from lysosomal particles (Dingle, 1961; see also
Chapter 17).
Studies with compounds structurally related to vitamin A (Fell,
Dingle and Webb, 1962) have shown that the molecular specificity
for the action of the vitamin is very high. Small alterations in structure
greatly decreased, or abolished entirely the action of the vitamin in the
organ-culture system. This specificity, which is very similar to that
found in the animal, also applies to the liberation of enzymes from
isolated lysosomes, and to the action of vitamin A on cell membranes
(Dingle and Lucy, 1962).
The work on the action of the vitamin, initiated in the Tissue
Culture studies by Fell and Mellanby (1952), provides an example in
which the Tissue Culture method has proved almost ideal for the
elucidation of a physiological problem, and has given grounds for a
new hypothesis for the mechanism of action of the vitamin when added
in excess. It is probable that the initial action of the vitamin is to alter
the structure of lipoprotein membranes of cells and intracellular
particles, and this is followed by a change in enzyme distribution,
which gives rise to the observed intracellular and extracellular alterations.
Whilst these experiments show a role for vitamin A in the control
of tissue matrix, by the release of hydrolytic enzymes, another possible
function of the vitamin in mucopolysaccharide metabolism has been
demonstrated in recent work by Wolf and his colleagues. Thus, Wolf,
Varandani and Johnson (1961) obtained an enzyme preparation that
contained vitamin A from the mucosa of the pig colon, which in the
presence of
3 5
S 0 4
2 - and
1 4
C-glucose, catalysed the synthesis of mucopolysaccharides. Moreover, vitamin A deficient pigs yielded an enzyme
of low activity which could be increased by the addition of vitamin A.
Previously Wolf and Varandani (1960) and Varandani, Wolf and Johnson (1960) had shown that the block in mucopolysaccharide synthesis
observed in colon segments and homogenates of the vitamin-deficient
animal occurred at the sulphate activation step, i.e. in the synthesis
of 3'-adenosine-5'-phosphosuiphate and that this deficiency could be
corrected by the in vitro addition of vitamin A . In agreement with this,
the reduced content of mucopolysaccharides in the colon of the vitamin
A deficient rat was found to be due mainly to a decrease in the amount
of galactosamine-containing polysaccharides (Moretti and Wolf,
1961) (cf. also the action of vitamin A in causing the mucous metaplasia
of cultured skin: Chapter 17).
The techniques of Tissue Culture provide a means for the investigation of the direct actions of hormones on target tissues and cell types.
At present, however, mucopolysaccharide distribution in these systems
J . T . D I N G L E A N D M . W E B B
of acid-hydrolases from lysosomal particles (Dingle, 1961; see also
Chapter 17).
Studies with compounds structurally related to vitamin A (Fell,
Dingle and Webb, 1962) have shown that the molecular specificity
for the action of the vitamin is very high. Small alterations in structure
greatly decreased, or abolished entirely the action of the vitamin in the
organ-culture system. This specificity, which is very similar to that
found in the animal, also applies to the liberation of enzymes from
isolated lysosomes, and to the action of vitamin A on cell membranes
(Dingle and Lucy, 1962).
The work on the action of the vitamin, initiated in the Tissue
Culture studies by Fell and Mellanby (1952), provides an example in
which the Tissue Culture method has proved almost ideal for the
elucidation of a physiological problem, and has given grounds for a
new hypothesis for the mechanism of action of the vitamin when added
in excess. It is probable that the initial action of the vitamin is to alter
the structure of lipoprotein membranes of cells and intracellular
particles, and this is followed by a change in enzyme distribution,
which gives rise to the observed intracellular and extracellular alterations.
Whilst these experiments show a role for vitamin A in the control
of tissue matrix, by the release of hydrolytic enzymes, another possible
function of the vitamin in mucopolysaccharide metabolism has been
demonstrated in recent work by Wolf and his colleagues. Thus, Wolf,
Varandani and Johnson (1961) obtained an enzyme preparation that
contained vitamin A from the mucosa of the pig colon, which in the
presence of
3 5
S 0 4
2 - and
1 4
C-glucose, catalysed the synthesis of mucopolysaccharides. Moreover, vitamin A deficient pigs yielded an enzyme
of low activity which could be increased by the addition of vitamin A.
Previously Wolf and Varandani (1960) and Varandani, Wolf and Johnson (1960) had shown that the block in mucopolysaccharide synthesis
observed in colon segments and homogenates of the vitamin-deficient
animal occurred at the sulphate activation step, i.e. in the synthesis
of 3'-adenosine-5'-phosphosuiphate and that this deficiency could be
corrected by the in vitro addition of vitamin A . In agreement with this,
the reduced content of mucopolysaccharides in the colon of the vitamin
A deficient rat was found to be due mainly to a decrease in the amount
of galactosamine-containing polysaccharides (Moretti and Wolf,
1961) (cf. also the action of vitamin A in causing the mucous metaplasia
of cultured skin: Chapter 17).
The techniques of Tissue Culture provide a means for the investigation of the direct actions of hormones on target tissues and cell types.
At present, however, mucopolysaccharide distribution in these systems