May 2, 2018 - much like vitamin D, when a deficiency is at ... HT, Severson DL, Stansbie D, ... for Treatment of Iron De
CHELATION & THE KREBS CYCLE KREBS CYCLE INTERMEDIATES AND NUTRIENT TRANSPORT
INTRODUCTION Millions of people across the
FACT… Bioavailability is
The Krebs Cycle
defined as the
globe supplement their diets with macro and trace minerals. When
Our bodies have the amazing
proportion of an
the diet is lacking in these
ability to turn sugars, fats, and
ingredient or other
important nutrients, health issues
amino acids from the foods we
substance that enters
ensue and is a very good idea to
eat into energy for later use.
consume a non-food mineral
Back in 1937, Hans Adolf Krebs
source. There’s only one catch…
won the Nobel Prize for
how do we know the minerals are
discovering an amazing feature
body and so is able
going to end up where we want
that our bodies possess. All
to have an active
them to end
JUST BECAUSE YOU
up in our bodies. Just because you swallow a
effect. All substances
well as all
that enter our mouths
other
DOESN’T NECESSARILY
aerobic
MEAN ITS GOING TO GO
doesn’t
WHERE IT’S SUPPOSED TO.
necessarily
introduced into the
humans, as
SWALLOW A MINERAL
mineral
the circulation when
organisms,
have a statistical probability of getting
have the
to where they need
ability to
to go (or where we
break down
desire them to go)
mean its going to go where it’s
macronutrients into a single
supposed to. This is one of the
common molecule (pyruvate)
great dilemmas of human
which gets rearranged and
physiology and nutrition. Now if
oxidized to yield all sorts of other
there were only a liaison, a
valuable biomolecules that the
substance getting to
chaperone if you will, that
body can use. This series of
its physiological
escorted the minerals to where
reactions is called the Krebs
destination depends
they needed to go with much
Cycle (aka. Citric Acid Cycle or
more efficiency than if left to
Tricarboxylic Acid Cycle). Each
widely on a myriad of
themselves. Well, in fact our
turn of the Krebs Cycle, taking
body’s biochemistry does in fact
place within the mitochondria
make molecules that can take
(the engine of each eukaryotic
these minerals to where they
cell) and is largely regulated by
need to go. Introducing the
calcium and other influencers
intermediates to the Krebs Cycle.
1,2, makes molecules of stored energy that the body can use
once they are swallowed. The likelihood of a given
biological variants.
Krebs Cycle Intermediates and Nutrient Transport (GDP, NADH, FADH). This series of
a mate to partner up with. When
they end up passing right along
chemical reactions also yields
partnered up, this attraction is
through the intestinal tract in
intermediates that provide a
typically in the form of an ionic
which little to nothing actually
template for making a plethora
bond. This type of bond is very
makes it into the bloodstream.
of other molecules that are
strong due to each partner
This is where a good chaperone
critical for normal physiology.
staying extremely close to one
comes into play. As stated earlier,
another because they’re both
intestinal uptake seems to be
fighting over an electron.
favored when the chaperone is
The Bioavailability Problem
an organic molecule (especially Bioavailability is defined as the
Chelation
amino acids or intermediates of
proportion of an ingredient or
When a charged atom (i.e.
the citric acid cycle) as opposed
other substance that enters the
mineral) partners up with a non-
to an inorganic molecule21,22.
circulation when introduced into
metallic molecule, a special type
Inorganic molecules tend to drop
the body and so is able to have
of bond is formed called a
off the mineral at the wrong spots
an active effect. All substances
chelate. This becomes very
along the intestinal tract and
that enter our mouths have a
important in the bioavailability of
force the mineral to compete for
statistical probability of getting to
minerals. Now the questions
absorption with other minerals,
where they need to go (or where
becomes, what are the best
including themselves, at that
we desire them to go) once they
natural substances to chelate
absorption site6. Think of it as if
are swallowed. The likelihood of a
minerals with? Minerals are
you were dropped off at the
given substance getting to its
usually chelated to inorganic or
wrong bus stop and still had to
physiological destination
organic compounds. Inorganic
fight the crowd to get on the bus.
depends widely on a myriad of
compounds typically are oxides,
Organic chaperones such as
biological variants. With that
phosphates, sulfates, etc.
amino acids and Krebs Cycle
being said, what is the likelihood
Organic compounds are pretty
intermediates have a way of
of a mineral getting to its target
much every other compound
carrying the mineral through the
tissue.
found in nature that contains
intestinal wall and into the
So, what are minerals and where
carbon. It turns out that a mineral
bloodstream intact, only to then
do they come from? Minerology
actually has a better chance of
to release them to their assigned
tells us that minerals are
getting to its target tissue when it
serum transport vesicles to be
crystalline solids that are
is chelated to an organic
taken to their final destination7.
produced from non-biological
compound rather than an
Total serum mineral distributions
processes and have one and
inorganic one4,5. The problem
typically range from a small
only one unique composition3.
lies when the mineral enters the
portion still being bound to their
Think of minerals as clusters of a
duodenum from the stomach.
organic chelate chaperone, a
single atom (usually multivalent
Naked minerals do just fine in
larger portion being bound to
cations) that exists as a solid
their soluble state when floating
serum proteins, and a nominal
chunk. Once dissolved or freed
around in the stomach due to the
amount as in its free ionic state8.
from the solid it’s stuck to, the
low pH of the gastric juices.
single positively charged atom is
However, once the pH increases,
The Krebs Cycle Cast of
now naked and carries a charge.
as in the proximal and distal
Characters
Because the atom wants to obey
sections of the duodenum, these
the octet rule, these naked atoms
unbound, or loosely bound,
When a molecule of pyruvate
usually don’t last very long being
minerals cluster together and
enters the mitochondrial matrix
single – they immediately look for
precipitate. When this happens,
Krebs Cycle Intermediates and Nutrient Transport and links up with a molecule of
Alpha-ketoglutarate
bitten into. But besides being just
oxaloacetate to form citrate, an
A precursor to the amino acid
a sour molecule, citrate is the
amazing series of stepwise
glutamic acid, this intermediate
Krebs Cycle product of the
reactions take place to
plays a pivotal role in nitrogen
condensation of oxaloacetate
rearrange citrate to make all sorts
metabolism. Alpha-ketoglutarate
and acetyl-CoA, which then can
of fun intermediates as well as
has been proven to decrease
be transported out of the
different energy-storing
protein catabolism and increase
mitochondria and then cleaved
molecules. These Krebs Cycle
protein synthesis to enhance
again to begin the fatty acid
intermediates have unique
bone tissue formation in skeletal
synthesis route (which may be a
physiological features and
muscle and can be used in
good or bad thing). Citrate also
functions outside of just being the
clinical applications10. Further
plays a role in hydroxyapatite
result of citrate rearrangement.
research also indicates that it has
formation13, a vital component
The stepwise bond breaking and
the potential to alleviate
of human bone. Further, if making
bond forming of citrate yields:
intestinal inflammatory responses
healthy bones weren’t enough,
aconitate → isocitrate → alpha
and improve epithelial restitution
citrate also has been shown to
ketoglutarate → succinyl CoA →
and nutrient-sensing ability under
aid in sustaining the health of
succinate → fumarate → malate
stress injury11 (prevent intestinal
other tissues by decreasing brain
→ oxaloacetate. These are what
epithelial damage).
lipid peroxidation and
are known as the Krebs Cycle intermediates.
inflammation as well as Malate
protecting against liver
The precursor to oxaloacetate,
damage14.
What is so special about these
malate (in this case, malic acid) is
intermediates?
the sour-tasting compound found
Succinate
Some of the intermediates to the
in most fruits and is used as a
During the Krebs Cycle, alpha-
Krebs Cycle have a unique ability
food additive. Besides playing a
ketoglutarate gets tweaked by 2
to take certain amino acids and
vital role in putting more pyruvate
different enzymes to become
turn them into energy9, whereas
back into the Krebs Cycle to
succinate. This now 4-carbon
some intermediates can simply
produce more oxaloacetate,
intermediate has a couple of
turn themselves into energy via
malate has been shown to have
roles to play in the human body.
the gluconeogenic pathway. This
other benefits. Due to its ability to
Succinate plays a unique role as
can be especially helpful during
reduce inflammation and
the gate keeper for a particular
times of increased stress, exercise,
platelet aggregation, malate has
pathway that involves the Krebs
starvation, or disease. There are
been suggested to have pretty
Cycle in which GABA is
times however, during these
amazing cardioprotective
synthesized and recycled15.
situations, where the Krebs Cycle
effects12. Not to mention its role
Although there are many other
process slows down drastically. If
in β-oxidation of fatty acids (fat
roles that succinate plays in
and when this happens, a myriad
burning). This cannot happen
human biochemistry, the main
of physiological problems can
without malate’s involvement in
factor in which succinate is the
occur. Much research has been
the Krebs Cycle.
Krebs Cycle hero is the fact that
done to show how
the majority of the metabolism of
supplementation of these key
carbohydrates, amino acids,
players can improve such
Citrate
fatty acids, cholesterol, and
negative physiological
Like malic acid, citric acid is the
heme in the human body rely on
conditions.
main culprit for the sour taste
the temporary formation of
experienced when a citrus fruit is
Krebs Cycle Intermediates and Nutrient Transport succinate16. A pretty impressive
Again, no stranger to any cell in
a lot of the irritation and
role for one tiny molecule.
the human body, these
guesswork thankfully is quickly
chaperones are recognized and
coming to an end due to the
Fumarate
taken up by passive or active
help of our new-found friends, the
Fumarate is the intermediate
transport – with or without their
intermediates of the Krebs Cycle.
between succinate and malate
guests. Considering that the Krebs
in the Krebs Cycle. As well as
Cycle molecules carry and drop
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off minerals to target cells as well
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HT, Severson DL, Stansbie D,
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Krebs Cycle Intermediates and Nutrient Transport
Chelation & the Krebs Cycle KREBS CYCLE INTERMEDIATES AND NUTRIENT TRANSPORT
Chelation & the Krebs Cycle Krebs Cycle Intermediates and Nutrient Transport Prepared by:
Chad Brey, Research & Development Chemist on May 2nd, 2018 Chad Brey, a California State University, Northridge alumnus, has formulated dietary supplements and composed technical articles for various clients for many years and has made it his passion. Chad has formulated and developed small and large molecules in research and development laboratories since 2003 and continues to consult others in the field of R&D to this day.
