Chemistry Reference
In-Depth Information
hydroxylation reactions and play a role in the metabo-
lism of drugs and toxic substances. Of these enzymes,
sulfi te oxidase is the only one that is essential to human
health.
Only one case of molybdenum defi ciency has been
attributed to dietary molybdenum (Abumrad
et al
.,
1981). A man with Crohn's disease who was on total
parenteral nutrition (TPN) for 18 months developed
symptoms including tachycardia, headaches, and
nightblindness 6 months before his death. Biochemi-
cal abnormalities included elevated plasma methio-
nine, low serum uric acid, high urinary thiosulfate,
low urinary uric acid, and low urinary sulfate. These
abnormalities were reversed after administration of
ammonium molybdate.
Metabolic defects have been related to molybde-
num metabolism but are not associated with dietary
intake. These defects are rare. More than 100 infants
have been identifi ed who lack functioning sulfi te oxi-
dase. The patients had either a defect in the gene cod-
ing for the sulfi te oxidase enzyme or, more often, a
genetic defi ciency in the molybdenum cofactor (John-
son, 1997; Turnlund, 2002). Both defects are autosomal
recessive traits. Those with molybdenum cofactor
defi ciency are defi cient in all three molybdoenzymes
due to lack of functional molybdopterin. The serious
symptoms are due to lack of functional sulfi te oxidase.
Symptoms include severe brain damage, resulting in
death at an early age. The defects can be diagnosed
in early pregnancy through chorionic villus sampling
(Higdon, 2003). Biochemical abnormalities listed in
the preceding paragraph are found in these condi-
tions, as well as seizures, mental retardation, brain
atrophy and lesions, and dislocated lenses (Johnson,
1997). Classic xanthinuria is also an autosomal reces-
sive trait and is due to either a defect in xanthine oxidase
or both xanthine oxidase and aldehyde oxidase, but
not sulfi te oxidase. It is much more common than
molybdenum cofactor defi ciency but is not a lethal
defect.
Molybdenum defi ciency has been produced in
goats when on a diet with a molybdenum content
of only 24
On chicken farms, birds displayed a number of
symptoms characterized by the loss of feathers,
disorders in the ossifi cation of long bones, and changes
in joint cartilage, leading to complete immobility.
This seemed to be due to a molybdenum defi ciency,
because addition of molybdenum to the diet in doses
of 0.2-2.5 mg/kg eliminated the preceding symptoms
(Bains and Mc Kenzie, 1975; Payne and Bains, 1975),
but results require experimental examination.
5.6 Dietary Requirements and
Recommendations
The fi rst dietary molybdenum recommendations
for humans were made in the United States in 1980
(National Research Council, 1980). Because inadequate
information was available to establish a Recommended
Dietary Allowance (RDA), an Estimated Safe and Ade-
quate Daily Dietary Intake (ESADDI) was introduced.
It was based on usual intake, which was estimated to
be 150-500
g/day. The ESADDI was revised down-
ward to 75-250
µ
g/day after lower estimates of die-
tary intake were reported (National Research Council,
1989). On the basis of controlled human studies in
young men, the minimum dietary requirement was
estimated at 25
µ
g/day (Turnlund
et al
., 1995b), which
agrees with estimates based on extrapolation from
nonruminant animal studies (Anke
et al
., 1985). In 2002
Dietary Reference Intakes (DRIs) were introduced for
molybdenum (Institute of Medicine, 2002). The DRIs
include an Estimated Average Requirement (EAR),
the intake that meets the requirement of half of the
healthy individuals in a age and gender group; a Rec-
ommended Dietary Allowance (RDA), the average
intake that meets the requirement of nearly all healthy
individuals intake; and a Tolerable Upper Intake Level
(UL), the highest intake that is likely to pose no risk of
adverse health effects for almost all individuals. The
EAR for adults was based on a requirement of 25
µ
µ
g/day,
with an added factor for bioavailability, or 34
µ
g/day.
The RDA was set at 45
µ
g/day for adults of all ages,
50
g/day for pregnant and lactating women, and
from 17
µ
g/kg dry weight (Anke
et al
., 1985). It
has been induced in chicks and rats, but only after
tungsten was added at a ratio of 1000:1 (Anke
et al
.,
1985).
Symptoms of molybdenum defi ciency were
observed in lambs in areas of New Zealand with low
molybdenum concentrations in the soil and simulta-
neous protein defi ciency. In these animals, signs of
renal lithiasis were observed, and the renal stones
were composed predominantly of xanthine. For this
reason the syndrome was called “xanthine disease”
(Ferrando, 1971).
µ
g/
day for those 14-18 years of age. When data are not
available to establish an RDA, an Adequate Intake (AI)
is established. An AI of 2
µ
g/day for children 1-3 years of age to 43
µ
µ
g/day was set for infants
0-6 months and 3
g/day for those 7-12 months based
on the usual intake of breast-fed infants. Because of
lack of availability of human data, the UL was based
on extrapolation from studies of reproductive effects
in rats and mice and using an uncertainty factor (UF)
of 30. The UL for adults was thus set at 2 mg/day. The
ULs for children 1-18 years of age ranged from 0.3-1.7
mg/day, and no UL was set for infants because of lack
µ
