Lecture: B-vitamins and metabolism, part 1

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INTRODUCTION TO B-VITAMINS:
ROLE OF B-VITAMINS IN
METABOLIC PATHWAYS
Sept 10, 2014
We get energy on a daily basis from
carbohydrates, lipids, and proteins.
What events must occur, to enable
us to employ these dietary components
for energy?
NIACIN is vitamin needed for a great many
events in energy metabolism.
Two forms of niacin in the diet are shown: these are
precursors for NADH and NADPH
NIACIN AS A COMPONENT
OF NADH AND NADPH:
These participate in >200
biochemical reactions that
are essential for health!
EACH RED ARROW
IS A STEP IN FORMATION
OF ATP FROM GLUCOSE,
THAT USES NIACIN
FADH2 is a riboflavin-dependent
component. The FADH2 produced
also contributes electrons
for ATP synthesis by the ETC
ROLE FOR
NIACIN
GLYCOLYSIS: The molecular steps are easily seen.
USEFUL EXERCISE:
Draw out the intermediates
in the TCA cycle
NAD+
Acetyl-CoA
NADH
CO2
O
O
H2C
H2C
O
C
CO
O
CO
alpha-ketoglutarate
H2C
CO
H2C
O
C
SCoA
succinyl-CoA
REACTION CATALYZED BY THE ENZYME
a-KETOGLUTARATE DEHYDROGENASE
(PANTOTHENIC ACID is involved, will be discussed)
From
TCA
NADH (which contains niacin) carries most of the electrons
from the TCA to the electron-transport chain.
The NAD+ is regenerated, to be used again MANY times.
This is VERY simplified, of course. It really just
shows the REACTANTS and the PRODUCTS.
The niacin functional group as a redox
donor/acceptor of electrons
H
CH3 - C - COOOH
NAD+
?
Lactate
Reaction catalyzed by LDH
NADH
CH3 - C - COOO
?
Pyruvate
Another reaction catalyzed by LDH
Glutamate is the main amino acid that donates nitrogen
to the urea cycle. NADH is required for this reaction.
Niacin (as NAD)
is required for the
metabolism of
ethanol.
The metabolic fate
of lysine – HOW MANY
niacin-dependent steps?
Amino acids are degraded
for energy in normal
metabolism, we will discuss
in some detail.
Notice the Acetyl-CoA product,
which can be used by the TCA
cycle to make ATP.
OTHER B-VITAMINS HAVE ESSENTIAL ROLES
IN ENERGY METABOLISM
Pantothenic acid: all
steps that use CoA
Thiamine
Riboflavin
Thiamine: as provided in the diet
SEPARATE
ENZYMES EXIST
TO ACTIVATE
EACH B-VITAMIN:
Thiamine is modified
by addition of
two PO4 groups
The active form of thiamine in metabolism
SEVERAL ENZYMES WORK TOGETHER IN THE
PYRUVATE DEHYDROGENASE COMPLEX:
WHAT IS THE FATE OF THE 3 CARBONS IN
THE INITIAL PYRUVATE MOLECULE?
Wet Beriberi: edema
is a common feature.
What is the
diagnostic challenge?
Pellagra: dermatitis is typical
Pellagra/before and after treatment with
high-dose niacin: which biochemical
steps are disturbed, that involve niacin?
This graphic shows that some
dietary tryptophan is converted
to NIACIN.
The yield is is about 1 mg of
niacin, for 60 mg of tryptophan.
Corn is a problem because
its niacin content is often not
bioavailable, and because corn
is low in tryptophan.
The niacin RDA (20 mg) is based
on a lot of our niacin (another
20 mg) coming from tryptophan.
People who cannot make niacin
are given about 50 mg/day.
MICRONUTRIENT DEFICIENCY:
Often very non-specific.
How can we be prepared to diagnose these disorders?
USEFUL STUDY ASSIGNMENT:
-Suppose you ate a VERY limited diet, with
foods that are NOT fortified. What nutrients
would be deficient?
-corn
-potatoes
-white rice
-wheat
This can happen during a famine, where there is a sharp
reduction in the diversity of the diet.
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