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Title
The effects of dietary niacin and riboflavin on voluntary intake
and
metabolism of ethanol in rats.
Author
Pekkanen L; Rusi M
Source
Pharmacol Biochem Behav, 11(5):575-9 1979 Nov
Abstract
The effects of dietary deficiency and excess of niacin and riboflavin
on voluntary drinking of 10% (v/v) ethanol were studied in male
rats.
The effectiveness of dietary deficiency and excess of both niacin
and
riboflavin on tissue levels of these vitamins was demonstrated
by
measurements of urinary N1-methylnicotinamide and blood glutathione
reductase (EC 1.6.4.2) activity. A high-niacin diet containing
75 mg
niacin/kg food decreased ethanol intake by about 36% compared
to the
control diet containing 15 mgniacin/kg. Niacin or riboflavin
deficiency
and a high-riboflavin diet containing 40 mg rtary levels of niacin
or
riboflavin did not influence on ethanol elimination rate or levels
of
blood acetaldehyde during ethanol oxidation. Therefore, blood
acetaldehyde was not responsible for the decreased ethanol intake
of
rats fed with a high-niacin diet. It was concluded that the increased
ethanol intake caused by dietary deprivation of B-vitamin complex
found
in earlier studies is not a result of deficiency of niacin or
riboflavin but niacin may be involved in the decrease in ethanol
drinking, which follows dietary B-vitamin complex supplementation.
Title
Effect of pyridoxine on histamine liberation and degranulation
of rat
mast cells
Author
Garcia M; González R
Source
Allergol Immunopathol (Madr), 7(6):427-32 1979 Nov-Dec
Abstract
Pyridoxine, one of the B vitamins, has been shown to be useful
in the
treatment of childhood bronchial asthma by Collip et al. (1975).
A
double-blind study with 76 asthmatic children followed for five
months
indicated significant improvement in asthma following pyridoxine
therapy (200 mg daily) and a reduction in dosage of bronchodilators
and
cortisone. Other reports have shown that nicotinamide, another
B
vitamin shows inhibitory activity in rat mast cell degranulation
and
histamine release (Bekier et al. 1974, Wiczolkowska and Maslinski,
1975, 1976). These results induced us to investigate if pyridoxine,
like nicotinamide or disodium cromoglycate, exhibits pharmacological
inhibitory activity in rat mast cell degranulation and histamine
release induced by antigen or other non-immunological stimulants.
We
found that pyridoxine at concentrations of 10 (-3) M, or greater
significantly inhibited rat mast cell degranulation and histamine
release induced by phospholipase A, compound 48/80, antigen (egg
albumin) or a mixture of dextran and phosphatidyl serine, respectively.
In these experimental models, pyridoxine shows a pharmacological
profile similar to nicotinamide and disodium cromoglycate, although
weaker than the latter. In spite of this, the lack of toxicity
of this
vitamin at relatively high doses (1 or 1.5 g), the possibility
that
other mechanisms of action may be involved, such as the improvement
in
tryptophan metabolism reported by Collip following pyridoxine
therapy,
suggest that this vitamine merits additional research.
Title
Coenzyme A metabolism in pantothenic acid-deficient rats.
Author
Reibel DK; Wyse BW; Berkich DA; Neely JR
Source
J Nutr, 112(6):1144-50 1982 Jun
Abstract
The pantothenic acid (PA) and coenzyme A (CoA) content of various
organs of rats maintained on a PA-deficient diet were determined.
The
PA content of heart' kidney' gastrocnemius and testes of rats
fed the
PA-deficient diet was reduced by greater than 90%' and liver
PA was
reduced by 70%. However' these low PA levels were sufficient
to
maintain tissue CoA at control levels. Although CoA levels were
maintained' the PA-deficient rats did not grow at normal rates
suggesting that low PA may effect growth rate by mechanisms other
than
by depressed CoA. PA-deficient rats were subJected to fasting
and
alloxan-diabetes to determine if increased CoA synthesis occurred
as in
normal animals. Both fasting and diabetes resulted in elevations
in
myocardial and liver CoA' which were comparable in rats fed a
PA-deficient diet or a regular diet. The Source of the
PA used for the
increase in tissue CoA in PA-deficient rats has yet to be determined.
Title
Coenzyme A metabolism in vitamin B-12-deficient rats.
Author
Brass EP; Tahiliani AG; Allen RH; Stabler SP
Address
Department of Medicine' University of Colorado Health Sciences
Center'
Denver 80262.
Source
J Nutr, 120(3):290-7 1990 Mar
Abstract
Vitamin B-12 (cobalamin) deficiency results in decreased
L-methylmalonyl-coenzyme A (CoA) mutase activity. The consequence
of
this defect on the cellular CoA pool was studied in rats with
functional vitamin B-12 deficiency induced by administration
of the
cobalamin analogue hydroxy-cobalamin [c-lactam or by dietary
vitamin
B-12 deficiency. Both types of vitamin B-12 deficiency were associated
with methylmalonic acidemia (100-300-fold increases in plasma
methylmalonic acid concentration compared with controls)' but
overall
fuel homeostasis was intact. Liver from rats treated with
hydroxy-cobalamin [c-lactam contained a threefold greater concentration
of total CoA (free CoA plus all acyl-CoA) compared with saline-treated
rats. Fractionation of the CoA pool revealed higher levels of
CoA'
propionyl-CoA' methyl-malonyl-CoA' acid-insoluble CoA' as well
as total
CoA in the rats treated with hydroxy-cobalamin [c-lactam compared
with
controls. Similar increases in liver CoA content were seen in
dietary
vitamin B-12 deficiency in both the fed and fasted states. To
examine
the hypothesis that sequestration of hepatic CoA as propionyl-CoA
and
methylmalonyl-CoA could increase CoA biosynthesis' the effect
of
propionate on CoA biosynthesis was studied in hepatocytes isolated
from
control rats. Propionate (1 mM) increased the formation of 14C-CoA
from
[14C pantothenate (10 microM) by 27% in the hepatocyte system.
When
butyrate (1 mM) was provided as substrate' propionate (10 mM)
increased
[14C CoA formation by 63%.(Abstract TRUNCATED AT 250 WORDS)
Title
Coenzyme metabolic therapy in infectious allergic myocarditis
Author
Mazurets AF; Gurevich MA; Kubyshkin VF; Dziuba MV; Vikharev NP
Source
Klin Med (Mosk), 73(5):41-3 1995
Abstract
A trial was performed of clinical efficacy of the coenzyme complex
incorporating piridoxalphosphate' cobamamide and phosphaden in
patients
with infectious allergic myocarditis. Myo- cardial dystrophy
and
correlations of the myocardial enzymatic status with blood lymphocytes
in the above patients were taken in consideration. Corrective
action of
metabolic therapy on myocardial bioenergy was coupled with positive
antiarrhythmic and cardiotonic effects. Cytochemical follow-up
investigations enabled long-term monitoring over the patients`
condition and further catamnesis.
Title
Diet therapy and coenzyme therapy in hereditary metabolic diseases
Author
Bickel H
Source
Monatsschr Kinderheilkd, 131(8):488-94 1983 Aug
Abstract
A greater number of inherited metabolic disorders can now be
treated
with special diets or cofactors. Recent progress is illustrated
by the
example of various hyperphenylalaninaemias (HPHE)' of maple syrup
urine
disease (MSUD) and of various homocystinurias (HCY). Of special
importance for the future is a severe embryopathy in infants
of mothers
with HPHE and its possible prevention by reintroducing a phenylalanine
- restricted diet for the mother before conception. Of considerable
scientific interest and therapeutic impact is also the treatment
of
patients with HPHE due to tetrahydrobiopterin deficiency. This
consists
in substituting the patients` metabolism with this cofactor of
phenylalanine hydroxylase as well as with neurotransmitters.
Cofactor
deficiencies have also been described in MSUD and HCY' and substitution
with high doses of thiamine and pyridoxin has been successful.
The
management of the acute metabolic derangement of neonatal MSUD
is a
great therapeutic challenge even to experienced metabolic centres.
Rational therapy for homocystinurias due to remethylation defects
is
still being explored. In siblings with methylenetetrahydrofolate
reductase deficiency we used leucovorin for the first time and
with
success.
Title
Coenzyme A metabolism.
Author
Robishaw JD; Neely JR
Source
Am J Physiol, 248(1 Pt 1):E1-9 1985 Jan
Abstract
The metabolism of coenzyme A and control of its synthesis are
reviewed.
Pantothenate kinase is an important rate-controlling enzyme in
the
synthetic pathway of all tissues studied and appears to catalyze
the
flux-generating reaction of the pathway in cardiac muscle. This
enzyme
is strongly inhibited by coenzyme A and all of its acyl esters.
The
cytosolic concentrations of coenzyme A and acetyl coenzyme A
in both
liver and heart are high enough to totally inhibit pantothenate
kinase
under all conditions. Free carnitine, but not acetyl carnitine,
deinhibits the coenzyme A-inhibited enzyme. Carnitine alone does
not
increase enzyme activity. Thus changes in the acetyl
carnitine-to-carnitine ratio that occur with nutritional states
provides a mechanism for regulation of coenzyme A synthetic rates.
Changes in the rate of coenzyme A synthesis in liver and heart
occurs
with fasting, refeeding, and diabetes and in heart muscle with
hypertrophy. The pathway and regulation of coenzyme A degradation
are
not understood.
Title
Relation of short-term pyridoxine-HCl supplementation to plasma
vitamin
B-6 vitamers and amino acid concentrations in young women.
Author
Kang-Yoon SA; Kirksey A
Address
Department of Foods and Nutrition' Purdue University' West Lafayette'
IN.
Source
Am J Clin Nutr, 55(4):865-72 1992 Apr
Abstract
Pyridoxal 5`-phosphate (PLP) is a coenzyme in many metabolic
transformations of amino acids and may play a role in their absorption
and transport. This investigation analyzed the effects of large
oral
doses (27 mg/d) of pyridoxine (PN)-HCl over 2 wk on plasma PLP
and
amino acid concentrations in 10 young women. Plasma PLP was 45
+/- 2
nmol/L (means +/- SE) initially and reached 377 +/- 12 nmol/L
after 7 d
of supplementation. A steady-state PLP concentration remained
as long
as daily PN-HCl supplementation was continued. Plasma glutamic
acid
concentration was significantly lower after 7 and 14 d of
supplementation whereas alpha-amino-N-butyric acid' alanine'
cysteine'
arginine' phosphoserine' and urea concentrations were significantly
higher' particularly alpha-amino-N-butyric acid and cysteine.
Altered
plasma amino acid profiles and increased plasma urea concentrations
in
response to supplementation suggested accelerated protein and/or
amino
acid metabolism.
Title
The effects of biotin deficiency on organic acid metabolism:
increase
in propionyl coenzyme A-related organic acids in biotin-deficient
rats.
Author
Liu YY; Shigematsu Y; Nakai A; Kikawa Y; Saito M; Fukui T; Hayakawa
K;
Oizumi J; Sudo M
Address
Department of Pediatrics' Fukui Medical School' Japan.
Source
Metabolism, 42(11):1392-7 1993 Nov
Abstract
Volatile organic acid levels in plasma and tissues and nonvolatile
organic acid levels in urine of biotin-deficient (BD) rats were
measured and compared with other factors of biotin deficiency.
Biotin
levels and the activities of propionyl coenzyme A (CoA) carboxylase
(PCC) in the livers of these rats were decreased' respectively'
to 22%
+/- 3% and 3.6% +/- 0.3% of the average values of pair-fed controls.
Plasma concentrations of propionate were higher (15 to 223
micrograms/mL) than those of controls (5 to 7 micrograms/mL)'
whereas
plasma levels of 3-methylcrotonate were only minimally increased
as
compared with those of controls. Concentrations of these volatile
acids
in the tissues were similarly increased' although those in brain
showed
less remarkable increases as compared with levels in other tissues.
In
the urine of BD rats' large amounts of organic acids derived
from
propionyl CoA' as well as those from 3-methylcrotonyl CoA' were
excreted. Plasma propionate levels were not apparently related
to the
severity of clinical symptoms' biotin levels' or carboxylase
activities' but were related to the amounts of urinary ketone
bodies'
lactate' and some of the organic acids derived from branched-chain
amino acids' including those from propionyl CoA.
Title
Effect of alpha-tocopherol on glutamic acid metabolism and
nicotinamide coenzyme levels in hepatocytes
Author
Iakhnina DN; Agabekova II
Source
Vopr Med Khim, 32(3):48-51 1986 May-Jun
Abstract
Activity of enzymes participating in metabolism of glutamate
and
content of nicotinamide nucleotides was studied in rat liver
tissue
within 24 hrs after intramuscular administration of alpha-tocopheryl
acetate at doses of 30 mg and 300 mg per kg of body mass. Excess
of the
vitamin was responsible for a decrease in the ratio NAD+/NADH
in
cytosol, for stimulation of glutamate dehydrogenase reaction,
for a
decrease of aspartate aminotransferase activity in mitochondria
and of
alanine aminotransferase activity in cytosol as well as for an
increase
of NADPH content.
Title
Nicotinamide coenzymes in the regulation of cellular metabolism
in
various types of diabetes
Author
Veliki i NN; Obrosova IG; Efimov AS; Babicheva EI; Sokil OP
Source
Vopr Med Khim, 38(4):45-52 1992 Jul-Aug
Abstract
Hypoglycemic and hypolipidemic effects of nicotinamide in
insulin-dependent and noninsulin-dependent types of diabetes
have been
investigated. Hypoglycemic effect of nicotinamide in alloxan-
and
streptozotocin-induced diabetes resulted in activation of NAD+
biosynthesis and corresponding alterations in the redox state
of free
nicotinamide coenzymes. Increase in the free NAD+/NADH ratio
was
accompanied by inhibition of key gluconeogenic enzymes and by
a
decrease in the rate of 2-14C-incorporation into glucose in liver
tissue and by inhibition of sorbitol formation in lens tissue.
Nicotinamide exhibited hypolipidemic effect in db/db mice with
noninsulin-dependent diabetes. The agent inhibited the enzyme
of
primary steps of lipogenesis' altered the structure of intercellular
CoA pool and lowered the rate of lipid biosynthesis in liver
tissue'
thus normalizing blood lipoprotein compositions.
Title
Influence of enzyme inducers and inhibitors of the metabolism
of
xenobiotics and of the coenzyme forms of vitamins B1 and B2 on
the
anti-inflammatory effect of voltaren
Author
Stanislavchuk NA; Pentiuk AA; Lychik GZ; Lychko AP; Lutsiuk NB
Source
Farmakol Toksikol, 51(2):69-71 1988 Mar-Apr
Abstract
In experiments on 245 male rats there was studied the influence
of an
inductor of xenobiotic metabolism enzymes, phenobarbital, an
inhibitor
of microsomal monooxygenases, cobalt chloride, and also coenzyme
forms
of vitamins B1 and B2, thiamine diphosphate and flavin mononucleotide
on the anti-inflammatory effect of voltaren evaluated according
to
inhibition of an increase of the limb edema, a decrease of pain
sensitivity, the blood level of fucose and the liver level of
malondialdehyde in rats with adjuvant arthritis. Phenobarbital
weakens
the anti-inflammatory action of voltaren but at the same time
cobalt
chloride and thiamine diphosphate potentiate the therapeutic
effect of
voltaren. Flavin mononucleotide fails to modify the effect of
voltaren
but decreases however its toxicity.
Title
Compartmentation of folate-mediated one-carbon metabolism in
eukaryotes.
Author
Appling DR
Address
Department of Chemistry and Biochemistry' University of Texas'
Austin
78712
Source
FASEB J, 5(12):2645-51 1991 Sep
Abstract
Folate coenzymes supply the activated one-carbon units required
in
nucleic acid biosynthesis' mitochondrial and chloroplast protein
biosynthesis' amino acid metabolism' methyl group biogenesis'
and
vitamin metabolism. Because of its central role in purine and
thymidylate biosynthesis' folate-mediated one-carbon metabolism
has
been the target of many anticancer drug therapies. This review
is a
summary of recent results that suggest that folate-mediated one-carbon
metabolism is highly compartmentalized in eukaryotic cells. Evidence
exists for compartmentation of folate coenzymes and their one-carbon
units between intracellular organelles' for substrate channeling
of
folate coenzymes' and for compartmentation by intracellular
folate-binding proteins. Metabolic' regulatory' and therapeutic
implications of these processes are discussed.
Title
Decreased brain choline uptake in older adults. An in vivo proton
magnetic resonance spectroscopy study.
Author
Cohen BM; Renshaw PF; Stoll AL; Wurtman RJ; Yurgelun-Todd D;
Babb SM
Address
Brain Imaging Center' McLean Hospital' Belmont' MA 02178' USA.
Source
JAMA, 274(11):902-7 1995 Sep 20
Abstract
OBJECTIVE--To test the hypothesis that uptake of circulating
choline
into the brain decreases with age' because alterations in metabolism
of
choline may be a factor contributing to age-related degenerative
changes in the brain. DESIGN--Cohort comparison in younger and
older
adults. PARTICIPANTS--SubJects were chosen consecutively from
lists of
healthy volunteers screened by medical and psychiatric interviews
and
laboratory tests. Younger adults (n = 12) were between the ages
of 20
and 40 years (mean age' 32 years)' and older adults (n = 16)
were
between the ages of 60 and 85 years (mean age' 73 years).
INTERVENTIONS--After fasting overnight' subJects received choline'
as
the bitartrate' to yield free choline equal to 50 mg/kg of body
weight.
Blood was drawn for determination of plasma choline concentration
by
high-performance liquid chromatography' and proton magnetic resonance
spectroscopy (1H-MRS) was performed to determine the relative
concentration of cytosolic choline-containing compounds in the
brain at
baseline and after ingestion of choline. MAIN OUTCOME MEASURES--Plasma
choline and cytosolic choline-containing compounds in the brain'
estimated as the ratio of the choline resonance to the creatine
resonance on 1H-MRS scans of the basal ganglia' were compared
following
blinded analyses of data from subJect cohorts studied at baseline
and 3
hours after choline ingestion. RESULTS--Levels of plasma choline
and
cytosolic choline-containing compounds in brain were similar
at
baseline in younger and older subJects. Following ingestion of
choline'
plasma choline concentration increased by similar proportions
(76% and
80%) in both younger and older subJects. Brain cytosolic
choline--containing compounds increased substantially in younger
subJects (mean increase' 60%; P < .001 vs baseline). Older
subJects
showed a much smaller increase in brain choline-containing compounds
(mean' 16%; P < .001 vs the increase in younger subJects).
CONCLUSION--Uptake of circulating choline into the brain decreases
with
age. Given the key role of choline in neuronal structure and
function'
this change may be a contributing factor in onset in late life
of
neurodegenerative' particularly dementing' illnesses in which
cholinergic neurons show particular susceptibility to loss.
Title
Choline in the treatment of rapid-cycling bipolar disorder: clinical
and neurochemical findings in lithium-treated patients.
Author
Stoll AL; Sachs GS; Cohen BM; Lafer B; Christensen JD; Renshaw
PF
Address
Psychopharmacology Unit' Brigham and Women`s Hospital' Boston'
Massachusetts 02115' USA.
Source
Biol Psychiatry, 40(5):382-8 1996 Sep 1
Abstract
This study examined choline augmentation of lithium for rapid-cycling
bipolar disorder. Choline bitartrate was given openly to 6 consecutive
lithium-treated outpatients with rapid-cycling bipolar disorder.
Five
patients also underwent brain proton magnetic resonance spectroscopy.
Five of 6 rapid-cycling patients had a substantial reduction
in manic
symptoms' and 4 patients had a marked reduction in all mood symptoms
during choline therapy. The patients who responded to choline
all
exhibited a substantial rise in the basal ganglia concentration
of
choline-containing compounds. Choline was well tolerated in all
cases.
Choline' in the presence of lithium' was a safe and effective
treatment
for 4 of 6 rapid-cycling patients in our series. A hypothesis
is
suggested to explain both lithium refractoriness in patients
with
bipolar disorder and the action of choline in mania' which involves
the
interaction between phosphatidylinositol and phosphatidylcholine
second-messenger systems. |
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