Vitamins and Minerals

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Vitamins and Minerals Sept 17, 2014
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THIAMINE DEFICIENCY MAY BE EASIER TO
DIAGOSE THAN SOME OF THE OTHER MICRONUTRIENT
DEFICIENCIES, BECAUSE LACTIC ACID ACCUMULATES IN
THE BLOODSTREAM. LACTIC IS VERY EASY TO MEASURE
ON A STANDARD CLINICAL CHEMISTRY ANALYZER
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From paper Thiamine deficiency and acidosis
Use of hemodialysis and bicarbonate is very
standard if the causes of acidosis is renal
failure!
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Thiamine-dependent steps in conversion of
pyruvate to ATP
Thiamine
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The first reaction (1) requires thiamine to go
forward. If this step is blocked, what happens
to the pyruvate?
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Paper on Anorexia Nervosa need to rely on
general symptoms for diagnosis
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NIACIN DEFICIENCY CAN BE DIAGNOSED (WITH
DIFFICULTY) BY A TEST FOR METABOLITES IN THE
URINE. I CAN PROVIDE REFERENCES TO THIS
PROCEDURE. WE CAN IN GENERAL CONCLUDE
THAT DIAGNOSIS OF MICRONUTRIENT DEFICIENCIES IS A
MAJOR CLINICAL CHALLENGE.
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BIOCHEMISTRY OF VITAMIN B6
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Form of Vit B6(PLP) that is part of enzymes. All
the other forms in the diet also support the B6
requirement (about 2 mg/day).
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The RDA for adults, for B6, is 2 mg. Vitamin
B6 is added to some foods (such as
breakfast cereal). One serving TOTAL cereal meets
the RDA one serving of Cheerios is 25 of the
RDA. By contrast, bakery products in the US are
enriched with thiamine, niacin, riboflavin, and
folate, but not usually B6. Good sources
chicken, beef, fish and other animal
products. Bananas, potatoes with skin, collard
greens, and some legumes, are also useful.
Deficiency is not common in the United States.
(The vegan diet may be somewhat low in B6) Milk
is not a very good source (0.5 mg/quart) and the
B6 is DEGRADED if milk is boiled to make formula
this may have caused infant seizures in the early
1950s.
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Americans burn 100 grams of amino
acids/day (derived from protein) for energy. That
is 400 calories sometimes 20 of total
energy! What step is necessary, for those amino
acids to be used for metabolic energy, such as
the synthesis of ATP?
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Pyruvate, and every molecule in the TCA cycle,
contains only carbon, hydrogen, and oxygen. But
amino acids all contain NITROGEN. What is the
strategy that is used?
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MOST OF THESE CAN BE USED FOR ENERGY, IF THE
AMINO GROUP IS REMOVED
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Donor amino acid
The chemistry of transamination begins with the
DONOR amino acid, which is going to provide the
amino group.
This is followed by a set of reactions with the
enzyme, which we will discuss.
Amino group from donor
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The amino group is is transferred to keto acid,
which becomes the new amino acid. The keto acid
is the ACCEPTOR OF the amino group.
New amino acid
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What happened with the FIRST amino acid? A
keto-acid is formed.
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AMINO KETO NEW KETO NEW AMINO
ACID ACID ACID
ACID
Beside a new amino acid (GLUTAMATE), a new
keto acid is formed (PYRUVATE). (the new keto
acid, from reaction series 1). This reaction
is done by the enzyme ALANINE TRANSAMINASE
(ALT). What can be done with pyruvate, in
metabolism?
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WE WILL DISCUSS THE DIAGRAM IN CLASS, WITH
DETAILS ON THE BOARD
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After several weeks of HepA infections, there is
a large release of alanine-transaminase (ALT) to
the bloodstream, from damaged liver cells. What
information does that provide about whats
happening inside the liver cell?
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Vitamin B6 (as PLP) is also a cofactor for the
DECARBOXYLASE reaction. VITAMIN B6 IS REQUIRED
TO CONVERT GLUTAMATE TO THE KEY
NEUROTRANSMITTER, GABA. What could happen if
there was a deficiency of B6?
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Plecko, et al, Human Mutation, 28 19-26,2007
These patients require 100 mg/day of vit B6 to
avoid seizures the RDA is 2 mg/day for healthy
people with normal metabolism. Why do they
require so much dietary B6?
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LYSINE CATABOLISM
L-PIPECOLIC ACID ACCUMULATES BECAUSE OF
THE LACK OF THIS ENZYME
Piperidine-6-carboxylate complexes with PLP,
and creates a PLP deficiency
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A large amount of piperidine-6-carboxylate
accumulates because of the enzymatic defect in
lysine catabolism. In the brain, this makes a
complex with B-6, and the brain has trouble
making enough GABA. The result is seizures,
because CNS function requires GABA. If these
people are given very large doses of B-6 (100
mg/day), then enough is supplied to the brain to
support GABA synthesis. There are a large number
of disorders, each affecting small numbers of
people, where those individuals require much
larger amounts of a vitamin or mineral to
maintain health, than do people without that
metabolic disorder. This would be an interesting
topic for class review.
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How common is B6 deficiency in humans? Its one
of the more widely-available B-vitamins, so
deficiency does not seem to be a major public
health problem (except of course for individuals
with metablic problems, such as accumulation of
pipecolic acid in the brain). In the early
1950s, when formula was sometimes BOILED to
achieve sterile baby food, there were some
infants who had seizures. We know that mechanism,
from the demonstrated role for B6 in sythesis of
GABA.
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OTHER KEY ROLES FOR VITAMN B6 -synthesis of
heme, starting with delta-amino- levulinic acid
(B6-deficiency can contribute to
anemia) -conversion of tryptophan to
niacin -folate metabolism (Critical
role!) -synthesis of several neurotransmitters