section 38.1
Fat-Soluble Vitamins
FIG U RE 38-3
Karyotype of a promyelocytic leukemic cell, with balanced reciprocal translocation between chromosomes 15 and 17,
t(15; 17). The rearranged chromosomes are identified by arrows. (Courtesy of Dr. Mark H. Bogart.)
therapy may also augment the degradation of the PML-
RARa fusion protein. Transgenic mice with a PML-RARa
fusion gene develop PML, which supports the pathogenic
role of the fusion protein in human PML.
Retinyl phosphate, acting as a sugar carrier in a manner
similar to that of dolichol phosphate (Chapter 16), may
be necessary for normal glycosylation of a subgroup of
essential glycoproteins. In vitamin A deficiency, synthe-
sis of some glycoproteins is decreased. Retinyl phosphate
and mannosyl phosphoryl retinol have been identified
in vivo
and have been synthesized
in vitro
using biological
preparations. In rat liver, GDP-mannose: retinyl phosphate
mannosyltransferase has its highest specific activity in the
endoplasmic reticulum. However, retinoic acid can fully
support growth in the whole animal even though it is not
converted to retinol and does not participate in sugar trans-
fer reactions.
More than 1500 retinoids have been synthesized. Two
in particular, 13-cA-retinoic acid (isotretinoin) and etreti-
nate (Figure 38-4), have generated considerable interest
as agents for the treatment of dermatological disorders.
13-cA retinoic acid inhibits sebum production, is the drug
of choice for treatment of severe cystic acne, and is useful
in the treatment of other forms of acne. Etretinate is used
in Europe for treatment of psoriasis and related disorders.
Hypo- and Hypervitaminosis A
Serious vitamin A deficiency is not a major public health
problem in North America; however, where poverty and
poor nutrition are common many persons suffer from
vitamin A deficiency with active corneal involvement.
This condition leads to permanent blindness in about half
of cases, and many of those affected are preschool chil-
dren. Night blindness occurs early in vitamin A deficiency.
There is a reduction in rhodopsin concentration, followed
by retinal degeneration and loss of photoreceptor cells.
Degenerative changes may be due to instability of free
opsin or may indicate an additional nutritive function for
retinaldehyde (or retinoic acid) in retinal cells. The degen-
erative changes of retinitis pigmentosa, a relatively com-
mon, inherited cause of blindness, closely resemble those
of vitamin A deficiency.
Ingestion of vitamin A in large excess of the RDA can
cause toxicity. Daily intake of more than 7500 retinol
equivalents (25,000 IU) is not recommended, and doses
in excess of 3000 retinol equivalents (10,000 IU) should
only be used with medical supervision. Acute toxicity after
FIG U R E 38-4
Structures of 13-ciV-retinoic acid (isotretinoin) (a) and etretinate (b),
synthetic retinoids used as pharmacological agents.
previous page 940 Bhagavan Medical Biochemistry 2001 read online next page 942 Bhagavan Medical Biochemistry 2001 read online Home Toggle text on/off