Understanding Cysteine, Cystine,
and Native Whey Proteins
Many whey protein products
on the market advertise their ability to affect glutathione production
within the body. This is a growing area of consumer interest due
to clinical studies heralding Glutathione’s role as the body’s
master antioxidant and defender against disease and aging.
Because the amino acid Cysteine
is the critical rate-limiting factor in the body’s ability
to produce Glutathione, its availability in whey protein has become
an area of competitive comparison among high-quality whey proteins.
This article is intended to help clear up any
confusion regarding the two forms of Cysteine and how it relates
to the quality and biological activity of a whey protein.
A “native” protein is a protein
that is still in its original, natural structure. It has not been
altered by heat, chemicals, enzyme action, or distress.
Therefore, it is imperative to understand that
a native protein represents the ideal biological function for which
it was designed by nature. In regard to whey protein, a native whey
protein would represent the exact form of protein that was intended
to nourish a newborn mammal from its mother’s milk.
Amino acids are critical to life, and have
a variety of roles in metabolism. One of their most important functions
is to serve as the building blocks of proteins. All proteins in
all species, from bacteria to humans, are constructed from the same
set of twenty amino acids.
A protein is formed by amino acid subunits
linked together in a chain. The bond between two amino acids is
called a peptide bond and the chain of amino acids is called a peptide
(20 amino acids or less), or a polypeptide (more than 20).
Figure 1: Primary Protein Structure
consists of one or more unique polypeptide chains. These chains
then undergo a folding process which results in a configuration
that is the most stable for its particular chemical structure and
environment. The final 3-D arrangement is called the protein’s
conformation and typically assumes a globular appearance. To understand
this very complex conformation, scientists describe four levels
of how the amino acid peptide chains arrange themselves: Primary,
Secondary, Tertiary, and Quaternary.
Primary Structure refers to the linear sequence
of amino acids that make up the polypeptide chain. This sequence
is determined by the genetic code. The bond between two amino
acids (a peptide bond) is formed by the removal of a water molecule
from the two different amino acids, forming a dipeptide. The sequence
of amino acids determines the way that the protein folds into
its final structure, or conformation. (See Figure 1)
Secondary Structure refers to the formation
of a regular pattern of twists or kinks of the polypeptide chain.
This pattern is due to hydrogen bonds forming between the atoms
of the amino acid backbone. (See Figure 1)
Tertiary Structure refers to the three dimensional
globular structure formed by the folding of these polypeptide
chains. This typically results in a compact globular structure.
The folding of the polypeptide chain is stabilized by multiple
weak, non-covalent interactions. (See Figure 1) These interactions
Hydrogen bonds that form when a Hydrogen atom is shared
by two other atoms.
Electrostatic interactions that occur between charged amino
acid side chains.
Hydrophobic/Hydrophilic interactions: During the folding
process, amino acids with a polar (water soluble) side chain
are often found on the surface of the molecule while amino
acids with non-polar (water insoluble) side chain are buried
in the interior. This affects the water solubility of a protein.
Quaternary Structure refers to the fact that
some proteins contain more than one polypeptide chain, adding
an additional level of structural organization
Figure 1: The Four Levels of
a Protein Structure Formation
bonds may also contribute to the stability of the folding structure.
The amino acid Cysteine is unique in that it has a Sulfur-Hydrogen
(thiol group) as part of its side chain (R group). Therefore, at
points where two Cysteines align within the folding process, a disulfide
bond (Sulfur-Sulfur) can form. This molecule formed by two bonded
Cysteines is called Cystine.
can be found in both forms within the naturally occurring native whey
protein. Because each protein folds into its unique and specific conformation
based upon its genetic code, a specific ratio of Cysteine to Cystine
is representative of an unaltered native whey protein.
human body is able to use both forms in the production of Glutathione.
Thus, it is important to nourish the body with this ratio as prescribed
by the naturally occurring native protein.
Cysteine is the preferred form for synthesis
of glutathione in the Lymphocytes and neurons, while Cystine is
the preferred form for the synthesis of glutathione in macrophages
Proteins can denature, or unfold, so that
their 3-D structure is altered or damaged, but their primary peptide
chain remains intact. (See Figure 3) Many of the interactions that
stabilize the 3-D conformation of the protein are relatively weak
and are sensitive to various factors including high temperature,
low or high pH, high ionic strength, or organic solvents. Proteins
vary greatly in the degree of their sensitivity to these factors.
Denaturation is a process in which proteins
or nucleic acids lose their 3-D structure (tertiary structure) by
application of some external stress or compound. The protein is
forced to literally unfold as shown below. (See Figure 3)
Figure 3: Denaturing of a Native
the native structure of a protein determines its biological function,
the protein can no longer fully perform its original function after
it has been denatured.
amino acid peptide chains may remain intact. However, the denatured
protein has now lost its native form, and will now re-associate
itself into varying random (non-native) structures.
As a part of that process, sulfur groups on
the Cysteines are likely to undergo oxidation to form disulfide
bonds thus creating additional Cystines that were not normally present
in the native form.
This drastically diminishes the availability
of naturally-occurring (native) Cysteine. As a result, the original
native whey protein ratio of Cysteine to Cystine is dramatically
shifted in favor of Cystine within the denatured protein structure.
Although the body can and does utilize Cystine,
it is a larger and less water-soluble molecule making it more difficult
to utilize than the native form of Cysteine.
Therefore, in order for the body to provide
proper levels of Cysteine to the lymphocytes and neurons, the macrophages
and astrocytes must reduce the Cystine into Cysteine. This requires
a multi-step process and decreases the efficiency of optimal glutathione
The natural design and structure of a native
whey protein specifies its intended biological function. However,
the native structure is fragile and requires great care to preserve
the integrity of its structure and biological function. The ultra-high
heat pasteurization methods used in the production of commercial
whey proteins severely denatures the native proteins and diminishes
the availability of naturally-occurring Cysteine.
Therefore, in order to achieve the full
spectrum of nourishment and biological function intended by nature,
whey protein should be consumed in its native, unaltered form.
The best non-denatured native whey protein on the market will give
your body the proper ratio of Cysteine and Cystine for maximum Glutathione