Human Salivary Amylase

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Current revision

Human Salivary Amylase

1 Introduction
2 Structure
3 Active Site
4 Ligands
5 Evolutionary Relationship

Introduction

Salivary amylase is an enzyme that hydrolyzes starch in the oral cavity of humans. This enzyme is produced by salivary glands, although the majority of amylases in humans are produced in the pancreas. It consists of a single polypeptide chain of 496 amino acid residues that weighs 56 kDa. The starches are hydrolyzed to yield maltose which can then be used to produce glucose. Studies have postulated that salivary amylase stimulates physiological responses that prepare the digestive system to metabolize and absorb nutrients ^[1]. Additionally, salivary amylase is shown to inhibit the biofilm formation of several bacterial species, indicating a possible role in preventing oral bacterial infections ^[2]. Interestingly enough, this enzyme not only exists in humans but in other omnivores and some herbivores. However, obligate carnivores, such as house cats, lack this oral enzyme ^[1].

Structure

Human salivary amylase is a protein consisting of a single chain made up of three domains, , , and . The overall structure of this protein is barrel shaped, much like the three individual domains of the protein. This structure is stabilized by several disulfide bridges. These disulfide bridges are seen between the cysteine residues at positions , , , , and positions .

Active Site

The forms a large, deep cleft where larger starches bind and are hydrolyzed into smaller ones. This is at the and the . This active site plays a role in the enzyme’s function as a processive enzyme. This means that salivary amylase does not immediately detach from its substrates and can carry out several rounds of hydrolysis before detaching. The mechanism for hydrolyzing starches involves a proton donor group, cleaving the glycosidic bond. Then, a nucleophile, , forms a covalent intermediate between the enzyme and substrate. This intermediate is then attacked by a hydroxyl ion, formed by , resulting in an unaltered enzyme and the products of hydrolysis.

Ligands

Human salivary amylase has two ligands, calcium and chlorine. There are three metal binding sites that bind calcium ^[3]. Studies that have investigated the function of these calcium ions have suggested that the presence of these ions greatly influences the thermostability of the enzyme ^[4]. This may be a result of the fact that the enzyme moves from the cooler oral cavity to warmer regions of the gastrointestinal tract; however, the lower pH of these regions may inactivate salivary amylase. These metal binding sites occur at the , the , the , and the . Aside from calcium, chloride ions can bind to salivary amylase and there are three binding sites for this ligand ^[3]. These chloride binding sites are found at the , the , and the . It is suggested that the negative charge associated with these chloride ions is essential for the maximal catalytic activity of the enzyme ^[5]. Other ions, such as nitrate, can bind to these chloride binding sites, however, their ability to allosterically activate salivary amylase is much weaker.

Evolutionary Relationship

There are many uncertainties that surround the evolutionary advantage of having an amylase produced and secreted in the oral cavity. The majority of amylases in humans are manufactured in the pancreas and sent to aid in starch digestion in the duodenum of the small intestines ^[6]. Although human amylases share sequence homology, they are coded by different genes. Studies have suggested that humans, along with some other animals, acquired the gene for a separate salivary amylase when foreign insertions caused the gene for pancreatic amylases to split ^[6]. Additionally, it is hypothesized that salivary amylase helps make starches more palatable by quickly decreasing the length of the polymer chains and therefore lowering the viscosity ^[1]. Furthermore, the early breakdown of these starches may release products that are detected in the oral cavity. The detection of these products activates physiological processes that prepare the digestive system to break down the incoming starches ^[1].

References

↑ ^1.0 ^1.1 ^1.2 ^1.3 Peyrot des Gachons C, Breslin PA. Salivary Amylase: Digestion and Metabolic Syndrome. Curr Diab Rep. 2016 Oct;16(10):102. doi: 10.1007/s11892-016-0794-7. PMID:27640169 doi:http://dx.doi.org/10.1007/s11892-016-0794-7
↑ Pajic P, Pavlidis P, Dean K, Neznanova L, Romano RA, Garneau D, Daugherity E, Globig A, Ruhl S, Gokcumen O. Independent amylase gene copy number bursts correlate with dietary preferences in mammals. Elife. 2019 May 14;8. pii: 44628. doi: 10.7554/eLife.44628. PMID:31084707 doi:http://dx.doi.org/10.7554/eLife.44628
↑ ^3.0 ^3.1 doi: https://dx.doi.org/10.2210/pdb1SMD/pdb
↑ Liao SM, Liang G, Zhu J, Lu B, Peng LX, Wang QY, Wei YT, Zhou GP, Huang RB. Influence of Calcium Ions on the Thermal Characteristics of alpha-amylase from Thermophilic Anoxybacillus sp. GXS-BL. Protein Pept Lett. 2019;26(2):148-157. doi: 10.2174/0929866526666190116162958. PMID:30652633 doi:http://dx.doi.org/10.2174/0929866526666190116162958
↑ doi: https://dx.doi.org/10.1110/ps.0202602
↑ ^6.0 ^6.1 Pajic P, Pavlidis P, Dean K, Neznanova L, Romano RA, Garneau D, Daugherity E, Globig A, Ruhl S, Gokcumen O. Independent amylase gene copy number bursts correlate with dietary preferences in mammals. Elife. 2019 May 14;8. pii: 44628. doi: 10.7554/eLife.44628. PMID:31084707 doi:http://dx.doi.org/10.7554/eLife.44628

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@@ Line 4: / Line 4: @@
 == Introduction ==
-Salivary amylase is an enzyme that hydrolyzes starch in the oral cavity of humans. This enzyme is produced by salivary glands, although the majority of amylases in humans are produced in the pancreas. It consists of a single polypeptide chain of 496 amino acid residues that weighs 56 kDa. The starches hydrolyzed yield maltose which can then be used to produce glucose. Studies have postulated that salivary amylase stimulates physiological responses that prepare the digestive system to metabolize and absorb nutrients (REF). Additionally, salivary amylase is shown to inhibit the biofilm formation of several bacterial species, indicating a possible role in preventing oral bacterial infections (REF). Interestingly enough, this enzyme not only exists in humans but in other omnivores and some herbivores. However, obligate carnivores, such as house cats, lack this oral enzyme (REF).
+Salivary amylase is an enzyme that hydrolyzes starch in the oral cavity of humans. This enzyme is produced by salivary glands, although the majority of amylases in humans are produced in the pancreas. It consists of a single polypeptide chain of 496 amino acid residues that weighs 56 kDa. The starches are hydrolyzed to yield maltose which can then be used to produce glucose. Studies have postulated that salivary amylase stimulates physiological responses that prepare the digestive system to metabolize and absorb nutrients <ref name="dig">DOI:10.1007/s11892-016-0794-7</ref>. Additionally, salivary amylase is shown to inhibit the biofilm formation of several bacterial species, indicating a possible role in preventing oral bacterial infections <ref name="bio">DOI:10.7554/eLife.44628</ref>. Interestingly enough, this enzyme not only exists in humans but in other omnivores and some herbivores. However, obligate carnivores, such as house cats, lack this oral enzyme <ref name="dig"/>.
 == Structure ==
-Human salivary amylase is a protein consisting of a single chain made up of three domains, A, B, and C. The overall structure of this protein is barrel shaped, much like the three individual domains of the protein. This multi domain structure is stabilized by several disulfide bridges. These disulfide bridges are seen between the cysteine residues at positions 28 and 86, 70 and 115, 141 and 160, 378 and 384, and positions 450 and 462.
+Human salivary amylase is a protein consisting of a single chain made up of three domains, <scene name='91/910719/A/1'>A</scene>, <scene name='91/910719/B/1'>B</scene>, and <scene name='91/910719/C/1'>C</scene>. The overall structure of this protein is barrel shaped, much like the three individual domains of the protein. This <scene name='91/910719/Multi/1'>multi domain</scene> structure is stabilized by several disulfide bridges. These disulfide bridges are seen between the cysteine residues at positions <scene name='91/910719/Di1/14'>28 and 86</scene>, <scene name='91/910719/Di2/3'>70 and 115</scene>, <scene name='91/910719/Di3/3'>141 and 160</scene>, <scene name='91/910719/Di4/2'>378 and 384</scene>, and positions <scene name='91/910719/Di5/2'>450 and 462</scene>.
 == Active Site ==
-The active site forms a large, deep cleft where larger starches bind and are hydrolyzed into smaller ones. This active site is at the aspartate residue at position 197 and the glutamate residue at position 233. This active site plays a role in the enzyme’s function as a processive enzyme. This means that salivary amylase does not immediately detach from its substrates and can carry out several rounds of hydrolysis before detaching. The mechanism for hydrolyzing starches involves a proton donor group, Glu 233 cleaving the glycosidic bond. Then, a nucleophile, Asp 197, forms a covalent intermediate between the enzyme and substrate. This intermediate is then attacked by a hydroxyl ion, formed by Glu 233, resulting in an unaltered enzyme and the products of hydrolysis.
+The <scene name='91/910719/Act/1'>active site</scene> forms a large, deep cleft where larger starches bind and are hydrolyzed into smaller ones. This <scene name='91/910719/Act/1'>active site</scene> is at the <scene name='91/910719/Act2/2'>aspartate residue at position 197</scene> and the <scene name='91/910719/Act1/1'>glutamate residue at position 233</scene>. This active site plays a role in the enzyme’s function as a processive enzyme. This means that salivary amylase does not immediately detach from its substrates and can carry out several rounds of hydrolysis before detaching. The mechanism for hydrolyzing starches involves a proton donor group, <scene name='91/910719/Act1/1'>Glu 233</scene> cleaving the glycosidic bond. Then, a nucleophile, <scene name='91/910719/Act2/2'>Asp 197</scene>, forms a covalent intermediate between the enzyme and substrate. This intermediate is then attacked by a hydroxyl ion, formed by <scene name='91/910719/Act1/1'>Glu 233</scene>, resulting in an unaltered enzyme and the products of hydrolysis.
 == Ligands ==
-Human salivary amylase has two ligands, calcium and chlorine. There are three metal binding sites per domain that bind calcium <ref name="pdb">DOI:10.2210/pdb1SMD/pdb</ref>. Studies that have investigated the function of these calcium ions have suggested that the presence of these ions greatly influences the thermostability of the enzyme (REF). This may be a result of the fact that the enzyme moves from the cooler oral cavity to warmer regions of the gastrointestinal tract; however, the lower pH of these regions may inactivate salivary amylase. These metal binding sites occur at the asparagine residue at position 100, the arginine residue at position 158, the glutamate residue at position 167, and the histidine residue at position 201.  Aside from calcium, chloride ions can bind to salivary amylase and there are three binding sites for this ligand <ref name="pdb"/>. These chloride binding sites are found at the arginine residue at position 195, the asparagine residue at position 298, and the arginine residue at position 337. It is suggested that the negative charge associated with these chloride ions is essential for the maximal catalytic activity of the enzyme. Other ions, such as nitrate, can bind to these chloride binding sites, however, their ability to allosterically activate salivary amylase is much weaker.
+Human salivary amylase has two ligands, calcium and chlorine. There are three metal binding sites that bind calcium <ref name="pdb">DOI:10.2210/pdb1SMD/pdb</ref>. Studies that have investigated the function of these calcium ions have suggested that the presence of these ions greatly influences the thermostability of the enzyme <ref name="cal">DOI:10.2174/0929866526666190116162958</ref>. This may be a result of the fact that the enzyme moves from the cooler oral cavity to warmer regions of the gastrointestinal tract; however, the lower pH of these regions may inactivate salivary amylase. These metal binding sites occur at the <scene name='91/910719/Cal1/2'>asparagine residue at position 100</scene>, the <scene name='91/910719/Cal2/2'>arginine residue at position 158</scene>, the <scene name='91/910719/Cal3/2'>glutamate residue at position 167</scene>, and the <scene name='91/910719/Cal4/1'>histidine residue at position 201</scene>. Aside from calcium, chloride ions can bind to salivary amylase and there are three binding sites for this ligand <ref name="pdb"/>. These chloride binding sites are found at the <scene name='91/910719/Cl1/1'>arginine residue at position 195</scene>, the <scene name='91/910719/Cl2/1'>asparagine residue at position 298</scene>, and the <scene name='91/910719/Cl3/1'>arginine residue at position 337</scene>. It is suggested that the negative charge associated with these chloride ions is essential for the maximal catalytic activity of the enzyme <ref name="chl">DOI:10.1110/ps.0202602</ref>. Other ions, such as nitrate, can bind to these chloride binding sites, however, their ability to allosterically activate salivary amylase is much weaker.
 == Evolutionary Relationship ==
-There are many uncertainties that surround the evolutionary advantage of having an amylase produced and secreted in the oral cavity. The majority of amylases in humans are manufactured in the pancreas and sent to aid in starch digestion in the duodenum of the small intestines (REF). Although human amylases share sequence homology, they are coded by different genes. Studies have suggested that humans, along with some other animals, acquired the gene for a separate salivary amylase when foreign insertions caused the gene for pancreatic amylases to split (REF). Additionally, it is hypothesized that salivary amylase helps make starches more palatable by quickly decreasing the length of the polymer chains and therefore lowering the viscosity (REF). Furthermore, the early breakdown of these starches may release products that are detected in the oral cavity. The detection of these products activates physiological processes that prepare the digestive system to break down the incoming starches (REF).
+There are many uncertainties that surround the evolutionary advantage of having an amylase produced and secreted in the oral cavity. The majority of amylases in humans are manufactured in the pancreas and sent to aid in starch digestion in the duodenum of the small intestines <ref name="gen">DOI:10.7554/eLife.44628</ref>. Although human amylases share sequence homology, they are coded by different genes. Studies have suggested that humans, along with some other animals, acquired the gene for a separate salivary amylase when foreign insertions caused the gene for pancreatic amylases to split <ref name="gen"/>. Additionally, it is hypothesized that salivary amylase helps make starches more palatable by quickly decreasing the length of the polymer chains and therefore lowering the viscosity <ref name="dig"/>. Furthermore, the early breakdown of these starches may release products that are detected in the oral cavity. The detection of these products activates physiological processes that prepare the digestive system to break down the incoming starches <ref name="dig"/>.

Human Salivary Amylase

From Proteopedia

Current revision