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Transcript
Vitamins and Minerals
Sept 18, 2013
BIOCHEMISTRY OF
VITAMIN B6
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).
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 1950’s.
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?
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?
MOST OF THESE
CAN BE USED
FOR ENERGY, IF
THE AMINO GROUP
IS REMOVED
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
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
What happened with
the FIRST amino acid?
A keto-acid is formed.
AMINO
ACID
KETO
ACID
NEW KETO
ACID
NEW AMINO
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?
WE WILL DISCUSS THE DIAGRAM IN CLASS,
WITH DETAILS ON THE BOARD
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 what’s
happening inside the liver cell?
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?
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?
LYSINE CATABOLISM
L-PIPECOLIC ACID
ACCUMULATES –
BECAUSE OF THE
LACK OF THIS
ENZYME
Piperidine-6-carboxylate
complexes with PLP, and
creates a PLP “deficiency”
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.
How common is B6 deficiency in humans?
It’s 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 1950’s, 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.
OTHER KEY ROLES FOR VITAMN B6:
-synthesis of heme, starting with delta-aminolevulinic acid
(B6-deficiency can contribute to anemia)
-conversion of tryptophan to niacin
-folate metabolism (Critical role!)
-synthesis of several neurotransmitters
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
From paper: Thiamine deficiency and acidosis
Use of hemodialysis and bicarbonate is very standard
if the causes of acidosis is renal failure!
Thiamine-dependent steps in conversion
of pyruvate to ATP
Thiamine
The first reaction (#1) requires thiamine to go forward.
If this step is blocked, what happens to the pyruvate?
Paper on Anorexia Nervosa: need to rely
on “general symptoms” for diagnosis
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.