N-Glycolylneuraminic acid
Encyclopedia
N-Glycolylneuraminic acid is a sialic acid
expressed in apes. It is absent in human tissues because of inactivation of gene encoding CMP-N-acetylneuraminic acid hydroxylase.
N-glycolylneuraminic acid is a sialic acid
molecule found in most mammals. Humans cannot synthesize Neu5Gc because the human gene CMAH is irreversibly mutated. The gene CMAH encodes for CMP-N-acetylneuraminic acid
hydroxylase, which is the enzyme responsible for CMP-Neu5Gc from CMP-N-acetylneuraminic (CMP-Neu5Ac) acid. This loss of the CMAH was estimated to have occurred two to three millions of years ago, which occurred just before the emergence of the genus Homo.
Neu5Gc is closely related to the commonly known Neu5Ac, but it differs by one atom in its structure. Neu5Ac differs by a single oxygen atom that is added in the cytosol of a cell. In many mammals, both of these molecules are transferred into the Golgi so that they may be added to many glycoconjugates
. However, in humans, Neu5Gc is not present.
by eliminating their Neu5Gc production. However, with the arise of Plasmodium falciparum, which is known as today’s malaria, humans were once again endangered as this new strain of the malaria had a binding preference to NeuG5c-rich erythrocytes in humans.
, the sialic acid can be transferred to the cytosol by a sialin transporter. Due to the fact that Neu5Gc differs from the human Neu5Ac by only one oxygen atom, cells will uptake the molecule as if it were native to the cell. Although the biochemical pathways don’t recognize this molecule as foreign the immune system does, which can bring about many problems.Epidemiological studies have shown a correlation between red meat consumption and increased risks of many diseases. These diseases include carcinomas, atherosclerosis
, and type-2 diabetes. Although not explicitly proven, it is suggested that it is the uptake of Neu5Gc from this diet that aggravates these diseases. Because of the anti- Neu5Gc antibodies that the human body carries, ingestion of Neu5Gc causes chronic inflammatory.
In recent findings, it has been discovered that all humans have NeuG5c-specific antibodies, often at high levels.
. Because Neu5Gc appears to be enhanced in naturally occurring tumors and fetal tumors, it is suggested that this uptake mechanism is enhanced by growth factors.
Sialic acid
Sialic acid is a generic term for the N- or O-substituted derivatives of neuraminic acid, a monosaccharide with a nine-carbon backbone. It is also the name for the most common member of this group, N-acetylneuraminic acid...
expressed in apes. It is absent in human tissues because of inactivation of gene encoding CMP-N-acetylneuraminic acid hydroxylase.
N-glycolylneuraminic acid is a sialic acid
Sialic acid
Sialic acid is a generic term for the N- or O-substituted derivatives of neuraminic acid, a monosaccharide with a nine-carbon backbone. It is also the name for the most common member of this group, N-acetylneuraminic acid...
molecule found in most mammals. Humans cannot synthesize Neu5Gc because the human gene CMAH is irreversibly mutated. The gene CMAH encodes for CMP-N-acetylneuraminic acid
N-Acetylneuraminic acid
N-Acetylneuraminic acid is the predominant sialic acid found in mammalian cells.This negatively charged residue is found in complex glycans on mucins and glycoproteins found at the cell membrane...
hydroxylase, which is the enzyme responsible for CMP-Neu5Gc from CMP-N-acetylneuraminic (CMP-Neu5Ac) acid. This loss of the CMAH was estimated to have occurred two to three millions of years ago, which occurred just before the emergence of the genus Homo.
Neu5Gc is closely related to the commonly known Neu5Ac, but it differs by one atom in its structure. Neu5Ac differs by a single oxygen atom that is added in the cytosol of a cell. In many mammals, both of these molecules are transferred into the Golgi so that they may be added to many glycoconjugates
Glycoconjugates
Glycoconjugates is the general classification for carbohydrates covalently linked with other chemical species.Glycoconjugates are very important compounds in biology and consist of many different categories such as glycoproteins, glycopeptides, peptidoglycans, glycolipids, and lipopolysaccharides...
. However, in humans, Neu5Gc is not present.
The Elimination of Neu5Gc in the Human Species
With the loss of NeuG5c and gain of excess Neu5Ac, it should have affected the interactions of pathogens and humans. Humans should have been less susceptible to Neu5Gc-binding pathogens and more susceptible to Neu5Ac-binding pathogens. It is suggested that human ancestors survived a then-prevailing NHH malariaMalaria
Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...
by eliminating their Neu5Gc production. However, with the arise of Plasmodium falciparum, which is known as today’s malaria, humans were once again endangered as this new strain of the malaria had a binding preference to NeuG5c-rich erythrocytes in humans.
Where can it be found?
Neu5Gc can be found in mammals, but trace amounts can be found in humans, even though the gene to encode for production of Neu5Gc was elminated long ago. These trace amounts come from consumption of animals in human diet. Mainly, the sources are red meats, like lamb, pork, and beef. It can also be found in dairy products, but to a lesser extent. Neu5Gc cannot be found in poultry and is found in only trace amounts in fish. This confirms that Neu5Gc is mainly found in foods of mammalian origin.What is the effect it has on humans?
Even though Neu5Gc cannot be produced by humans, it is still reported to be found in human cancers and fetal samples. This suggests that these Neu5Gc molecules must enter the human pathways through external sources, like through diets. As found in the observation of cultured human cells, the cells expressed Neu5Gc due to their uptake of animal products in the medium. By macropinocytosisPinocytosis
In cellular biology, pinocytosis is a form of endocytosis in which small particles are brought into the cell—forming an invagination, and then suspended within small vesicles that subsequently fuse with lysosomes to hydrolyze, or to break down, the particles...
, the sialic acid can be transferred to the cytosol by a sialin transporter. Due to the fact that Neu5Gc differs from the human Neu5Ac by only one oxygen atom, cells will uptake the molecule as if it were native to the cell. Although the biochemical pathways don’t recognize this molecule as foreign the immune system does, which can bring about many problems.Epidemiological studies have shown a correlation between red meat consumption and increased risks of many diseases. These diseases include carcinomas, atherosclerosis
Atherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
, and type-2 diabetes. Although not explicitly proven, it is suggested that it is the uptake of Neu5Gc from this diet that aggravates these diseases. Because of the anti- Neu5Gc antibodies that the human body carries, ingestion of Neu5Gc causes chronic inflammatory.
In recent findings, it has been discovered that all humans have NeuG5c-specific antibodies, often at high levels.
Mechanism of Uptake by Human Cells
Sialic acids are negatively charged and hydrophillic, so they don’t readily cross the lipid, hydrophobic membranes of cells. It is because of this that the uptake of Neu5Gc must occur through an endocytic pathway. More specifically, exogenous Neu5Gc molecules enter cells through clathrin-independent endocytic pathways with help from pinocytosis. After the Neu5Gc has entered the cell via pinocytosis, the molecule is released by lysosomal sialidase. The molecule is then transferred into the cytosol by the lysosomal sialic acid transporter. From here, Neu5Gc are available for activation and addition to glycoconjugatesGlycoconjugates
Glycoconjugates is the general classification for carbohydrates covalently linked with other chemical species.Glycoconjugates are very important compounds in biology and consist of many different categories such as glycoproteins, glycopeptides, peptidoglycans, glycolipids, and lipopolysaccharides...
. Because Neu5Gc appears to be enhanced in naturally occurring tumors and fetal tumors, it is suggested that this uptake mechanism is enhanced by growth factors.