CASE STUDY: Unique Sugars Create our Blood Types
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Ensuring that proteins are targeted to the proper cellular destination is critical in eukaryotic cell function. Not only is this necessary
for the protein to be in the proper place to carry out its function but also because certain post-translation modifications take place in
the secretory pathway. Therefore improperly processed proteins may be defective in their biochemical activity even if they are
located in the proper place in the cell. For example, the processing of the A and B antigens for specification of blood types is due to
post-translational modification by certain glycosyl transferases. Each antigenic determinant consists of structurally related
oligosaccharides present on both glycoproteins and glycolipids that are found on the surface of erythrocytes and other cell types.
The presence or absence of the glycosyl transferases determines which types of modifications occur on the O antigen. All people can
make the O antigen since it is found on all blood cells. If a person has type A blood, they have the glycosyl transferase enzyme, which
adds an N-acetyl galactosamine attached to the outer galactose residue on the O antigen. If a person has type B blood, they have the
glycosyl transferase enzyme, which adds a galactose residue to the outer galactose residue on the O antigen. If a person has type AB
blood, it really means that they have a mixture of A and B blood because they have both enzymes that modify the O antigen. A
person with AB blood with have a mixture of O antigens modified with either N-acetyl galactosamine or galactose.
One of the most important aspects of the ABO blood types is when considering donating or receiving blood. A person can create
circulating antibodies in their bloodstream to the non-present antigen types. For example, if a person has type A blood, he/she may
synthesize circulating antibodies to type B antigen so if he/she received type B blood. The antibody-antigen reaction would lead to a
significant immune response. Not only would the incorrect blood type be rejected, but the removal and recycling of those blood cells
could lead to greater illness. Recent studies have begun to use blood type groups as a genetic marker for other conditions, as there
may be some links between the blood type you inherit and other genes.
Questions:
1. If a person had the A gene but it was mutant and non-functional, what type of blood group antigen would they have circulating?
An individual with a mutant, non-functional A gene (encoding N-acetylgalactosamine transferase) would not express the A antigen and
would be classified as blood type O if no other glycosyltransferase enzymes (like B-transferase) are active to modify the H antigen.
If B-transferase is active and functional, they would express blood type B. This elucidation underscores the enzymatic basis for ABO
blood type determination and the genetic variability influencing these phenotypes.
2. For the person in question 1, what type of blood could they receive?
Blood type O red blood cells only
3. The glycosyl transferase enzymes are located in the Golgi complex, where are they synthesized and how are they processed?
The synthesis and processing of glycosyltransferases involve a series of steps beginning in the ER, where they are synthesized and
undergo initial folding and modifications, followed by further processing and maturation in the Golgi. This pathway ensures that
glycosyltransferases are correctly folded, modified, and localized to perform their specific functions in glycan synthesis, crucial for
various cellular processes including blood group antigen expression
4. If the glycosyl transferase enzymes are located in the Golgi complex, how is it that the blood group antigens are found on serum
proteins?
The blood group antigens are secreted proteins. That means they are processed through the entire secretory pathway. The glycosyl
transferase enzymes only serve to modify the antigens so they need to be located in the subcellular compartment in which the
modification occurs.
1. Brecher, M. E. and S. N. Hay, ABO Blood Type and Longevity. American Journal of Clinical Pathology, 2011. 135(1): p96-98.
2. Lipshutz Gs, M. S. Z. Q. and et al., ABo blood type–incompatible kidney transplantation and access to organs. Archives of Surgery,
2011. 146(4): p453-458.
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