Digestive system and pH level

This material is from my personal research into the significance of pH level. My particular area of interest is in the minerals required for absorption of nutrients, so names of minerals have been highlighted (bold) here, even though they were not highlighted in the source material. Where conflicting information on pH level was found; material from each source is provided.
 
~Mistral (formerly #72081)
 
4/19/07: WARNING: This material frequently mentions sulfation. Please be aware that G6PD deficiency is a common enzyme deficiency that causes severe anemia and other issues when taking medicines/supplements/foods containing significant amounts of sulphur.

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MOUTH/PHARYNX/ESOPHAGUS
 
The digestive process begins as food enters the mouth. In the first stage of digestion, the salivary glands secrete ptyalin (an alpha-amalyse digestive enzyme) which works to break down long-chain carbohydrates into successively smaller starches and ultimately maltose.(1) Salivary amylase (ptyalin) is a calcium-dependent metalloenzyme. A chloride ion is also involved. Salivary amalyse is most effective in the presence of chlorine and/or bromine.(1) It is slightly less effective in the presence of iodine, and least effective in the presence of sulfate and phosphate.(1) Saliva is only slightly acidic with a pH of 6.35-6.85(9), and the optimal pH for this enzyme is 6.7.(8) The throat and the esophagus secrete mucus to help in swallowing.(9)
 
The digestive process continues as food passes through the throat to the esophagus. The normal pH level of the esophagus is 6 to 7.(2, 3) "In the mouth, pharynx, and esophagus, pH is typically about 6.8, a very weak acid."(8) An esophageal pH level 4.0 or below is considered a gastro-esophageal reflux event.(3)
 
STOMACH
 
As the chewed food moves down the esophagus to the stomach, the stomach begins to secrete the digestive hormone gastrin in anticipation of a meal. The stomach normally has a pH between 5.0 and 6.0 before food arrives.(11) The process of activating gastrin requires sulfation.(6) Salivary amylase continues the digestion process until it is inactivated when stomach acid causes pH to drop below 5.0.(11,1) There are three types of cells in the stomach lining. Mucous neck cells produce mucus to protect the stomach lining. Chief cells secrete gastric lipase and pepsinogen. Pepsinogen is converted to pepsin in strong acidity (4). Parietal cells produce intrisic factor and Hydrochloric Acid (HCl). (9) The stomach lining consists of sulfated mucin proteins which influence the absorbability of nutrients, the adhesion/lubrication of proteins and peptides, and influence their form and election charge. The negative charge on the sulfated mucin lining of the stomach cause the food peptides to elongate as the sulfate groups within them, also negatively charged, repel from the negative charge of the mucin lining. Digestive conditions such as H. Pylori infection, irritable bowel syndrome, gut permeability, and autism have been tied to sulfation dysfunction in the mucin lining of the digestive system. Lack of sulfation (leading to lack of a negative charge) may also be linked to Candida (normally repeled by negative charge), and alterations in the gut flora.(6)

 
The distention of the stomach and pressure on the vagus nerve cause the release of gastrin.(4) Gastrin stimulates the parietal cells of the stomach to secrete hydrogen ions (H+) and chloride (Cl-) resulting in Hydrochloric Acid (HCl).(9) Calcium has been shown to increase gastric acid secretion from the parietal cells.(22) Stomach acid secretion continues until the pH level of the stomach contents is at least 3.0. This takes about 45 minutes in young healthy adults, however the amount of time required increases with age.(11) "The pH of the stomach in a normal, healthy human is in the 1-3 range."(16) Gastrin also stimulates the chief cells to secrete pepsinogen (8), an enzyme that initiates the digestion and breakdown of proteins."(16) High stomach acidity is required to activate pepsinogen.(16) The strong acidity of the stomach also causes the proteins in the chyme (food in the stomach) to partially unfold. The high acidity also kills many microbes, and stimulates the secretion of hormones that begin the flow of bile and pancreatic juices.(9)

 
"Chemoreceptors in the stomach monitor the pH of the stomach chyme."(9) When the pH level of the stomach contents reaches 3, secretion of gastrin is inhibited.(4) The pH within the stomach rarely, if ever, drops below 3.0. Pure stomach acid has a pH of 1.8 when it first enters the stomach, but is quickly diluted in the presence of food.(11) Typically, hydrochloric acid lowers the pH level of the stomach contents to a level between 2 to 3.(7) As gastric pH lowers, "blood pH correspondingly increases, particularly in those segments of the circulatory system associated with supplying the gastrointestinal tract. This increase in blood pH is known as the 'alkaline tide', and is caused by bicarbonate ions that are secreted into extracellular fluid of the stomach, then into venous blood."(16)

 
A magnesium-dependent H+/K+ ATPase or "proton pump" is involved in the secretion of stomach acid.

[The following material has been shortened and paraphrased slightly.]
"The current model for explaining acid secretion is as follows:

• Hydrogen ions are generated within the parietal cell from dissociation of water. The hydroxyl ions formed in this process rapidly combine with carbon dioxide to form bicarbonate ions, a reaction cataylzed by the zinc-dependent enzyme carbonic anhydrase.
• Bicarbonate is transported out of the basolateral membrane in exchange for chloride.
• Chloride and potassium ions are necessary for secretion of acid and are transported through conductance channels.
• A Hydrogen ion is pumped out of the cell, into the lumen, in exchange for potassium through the action of the proton pump; potassium is thus effectively recycled.
• Accumulation of osmotically-active hydrogen ions results in outward diffusion of water. The resulting gastric juice is 155 mM HCl and 15 mM KCl with a small amount of NaCl."
  (22)

The stomach acid itself does not digest protein. Rather, it activates the pepsinogen enzyme which then becomes pepsin.(10) Pepsin is only active within the pH range of 3.0 to 5.0.(11) Pepsin is one of several digestive enzymes involved in the breakdown of proteins. Its function is to break down proteins into peptides.(5, 7) Pepsin contains calcium, zinc, and iron.(10)
 
The chyme then leaves the stomach and enters the small intestine.
 
 
SMALL INTESTINES
 
DUODENUM
 
The chyme moves through the sphincter at the base of the stomach into the duodenum (the first part of the small intestine) in slow rhythmic contractions. Within two to four hours after eating a meal, the stomach has emptied its contents into the duodenum.(9) "The pH of the duodenum is 6 to 6.5. The majority of nutrients, vitamins, and drugs are absorbed in this 6 inch area of the gastrointestinal tract. In addition to water, mucus, and electrolytes, secretions from the liver and pancreas join secretions from the intestinal mucosa to facilitate digestion and absorption. The lining of the small intestines is composed of many villi, or finger like projections, which extend even more as projections called the brush border."(16) "Upon emptying into the small intestines, potential hydrogen (pH) changes dramatically from a strong acid to an alkaline content. The pancreas secretes bicarbonate to neutralize the acid from the stomach, and the mucus secreted in the tissue lining the intestines is alkaline which promotes digestive enzyme activity."(8) "The duodenal glands (Brunner's glands) are found only in the duodenum. They are tortuous and branching; their mucus-containing secretion has a pH of 5.8-7.6."(17) "The pH can reach 7 to 8 in this area."(16) "The mucosal tissue of the small intestines is alkaline, creating a pH of about 8.5, thus enabling absorption in a mild alkaline environment."(23) "Intestinal juice is slightly alkaline (pH 7.6). Together, pancreatic and intestinal juices provide a liquid medium that aids the absorption of substances from chyme as they come in contact with the microvilli."(9)
 
As partially digested food enters from the stomach, the mucous membrane of the duodenum manufactures the hormone secretin. Secretin decreases gastric secretions (9) and stimulates the pancreatic duct to release pancreatic juice.(17) Pancreatic juice contains pancreatin, "a mixture of the three digestive enzymes trypsin (which digests protein), lipase (which digests fat), and amylase (which digests starch)." The pH of the pancreatic juice is 7-8.(9) "Sodium bicarbonate makes pancreatic juice slightly alkaline (pH 7.1-8.2).(9) "Epithelial cells in pancreatic ducts are the source of the bicarbonate and water secreted by the pancreas. Bicarbonate is a base and critical to neutralizing the acid coming into the small intestine from the stomach. The mechanism underlying bicarbonate secretion is essentially the same as for acid secretion parietal cells and is dependent on the [zinc-dependent] enzyme carbonic anhydrase. In pancreatic duct cells, the bicarbonate is secreted into the lumen of the duct and hence into pancreatic juice."(13) "Carbonic anhydrases are enzymes that catalyze the hydration of carbon dioxide and the dehydration of bicarbonate: CO₂ + H₂O <-----> HCO₃^- + H⁺ Pancreatic duct cells do essentially the opposite [meaning they reduce acidity using the enzyme carbonic anhydrase], with bicarbonate as their main secretory product."(13)
 
"The two major pancreatic proteases are trypsin and chymotrypsin, which are synthesized and packaged into secretory vesicles as the inactive proenzymes trypsinogen and chymotrypsinogen. Trypsinogen is activated by the enzyme enterokinase, which is embedded in the [small] intestinal mucosa."(13) Pancreatic proteases such as trypsin and chymotrypsin complete digestion of proteins to their amino acid building blocks throgh proteolysis. Pancreatic proteases require sulfation. Without sulfation, instead of amino acids, peptides are found in the gastrointestinal tract.(6) Chymotrypsin contains a di-sulphide bond.(20) "Trypsin and chymotrypsin... cannot digest proteins and peptides to single amino acids. Some of the other proteases from the pancreas, for instance carboxypeptidase, have that ability, but the final digestion of peptides into amino acids is largely the effect of peptidases on the surface of small intestinal epithelial cells."(13) Pancreatic carboxypeptidase A enzymes (CPA-1 and CPA-2) are zinc-dependent metalloenzymes.(15,18) Enterokinase is the protease in the intestinal brush border that is responsible for generation of active trypsin from trypsinogen; trypsin, in turn, activates other digestive enzymes. The mature enteropeptidase has heavy and light chains, connected by a disulphide bond.(21)
 
In response to fat in the chyme, enteroendocrine cells in the duodenum also release cholecystokinin (CCK). CCK inhibits stomach emptying (9), activates the release of digestive enzymes in the pancreas, and stimulates the emptying of bile in the gall bladder.(8) The process of activating cholecystokinin requires sulfation.(6)
 
"The principal triglyceride-digesting enzyme in adults is called pancreatic lipase."(9) Pancreatic lipase is a constituent of pancreatic juice.(13) Sufficient quantities of bile salts must be present in the lumen of the intestine for pancreatic lipase to efficiently digest dietary triglycerides and to absorb the resulting fatty acids and monoglycerides. "This means that normal digestion and absorption of dietary fat is critically dependent on secretions from both the pancreas and liver."(13)
 
"Amalayse is present in the small intestines and works with other enzymes to complete the breakdown of carbohydrate into a monosaccharide which is absorbed into the surrounding capillaries of the villi."(8) Pancreatic amalyse is a calcium-dependent metalloenzyme.(1)
 
"In addition to the proteases, lipase and amylase, the pancreas produces a host of other digestive enzymes, including ribonuclease, deoxyribonuclease, gelatinase and elastase."(13)
 
Bile from the gallbladder(7) also enters the duodenum through the pancreatic duct. Bile acts as an emulsifier, eroding the edges of the larger complex fat globules into smaller globules for further digestion. "The introduction of lipase, along with the concentration of bile salts, in contact with the brush border of the mucosal cells, creates the correct environment for final stage breakdown of fats. Final absorption of fat into the body occurs in the villi."(8) "Bile, a yellow, brownish, or olive-green liquid has a pH of 7.6-8.6 and consists mostly of water and bile acids, bile salts, cholesterol, a phospholipid called lecithin, bile pigments, and several ions. Bile salts, which are sodium salts and potassium salts of bile acids, play a role in the breakdown and absorption of lipids. Acidic chyme entering the duodenum stimulates other enteroendocrine cells to secrete the hormone secretin into the blood, and CCK causes contraction of the wall of the gallbladder, which squeezes stored bile out of the gallbladder." (9) Bile from the gallbladder has an average 6.0 pH (5.6-8.0). Hepatic bile (where it originates) averages 7.5 pH (6.2-8.5)(16) Pancreatin-bile salts contain calcium, zinc, and iron.(10)
 
"Altogether, chyme remains in the small intestine for 3-5 hours. The completion of the digestion of carbohydrates, proteins, and lipids is a collective effort of pancreatic juice, bile, and intestinal juice in the small intestine."(9) 90% of the water in the chyme is absorbed in the small intestine.(9)
 
 
JEJENUM/ILEUM
 
"Further along the small intestine, beyond the duodenum, lies the jejunum and ileum. As we get further away from the stomach, the pH rises to about 7.5 in this region."(16) Most nutrient absorption takes place in the jejenum (with the exception of iron which is absorbed in the duodenum, and Vitamin B12 which is absorbed in the ileum). Digestive fats are absorbed into lymphatic (lacteal) capillaries, eventually ending up in the circulatory system. Other nutrients are absorbed into non-lacteal capillaries.(24) "Nutrients in the blood are transported to the liver via the hepatic portal circuit, or loop, where final carbohydrate digestion is accomplished in the liver. The liver accomplishes carbohydrate digestion in response to the hormones insulin and glucagon. As blood glucose levels increase following digestion of a meal, the pancreas secretes insulin causing the liver to transform glusose to glycogen, which is stored in the liver, adipose tissue, and in muscle cells, preventing hyperglycemia. A few hours following a meal, blood glucose will drop due to muscle activity, and the pancreas will now secrete glycogon which causes glycogen to be converted into glucose to prevent hypoglycemia."(8)
 
 
LARGE INTESTINES
 
"The first remnants of a meal reach the beginning of the large intestine in about four hours."(9) The pH of the large intestine ranges from 5.5 to 7.(16) "There is almost no digestion in the large intestine. The task of the colon is to absorb most of the remaining fluid and electrolytes from the chyme."(17) The large intestine continues the process of absorbing water from the feces. "The large intestine also absorbs ions, including sodium and chloride, and some vitamins."(9) In the large intestines, the chyme has a pH of 7.0-7.5.(17) The chyme remains in the large intestine 3 to 10 hours.(9)
 

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SOURCES
  (1)  Amylase
  http://en.wikipedia.org/wiki/Amylase

  (2)  24 hour, pH probe and pH impedance study
  http://www.livingwithreflux.org/page.php?pg=115

  (3)  Beyond the Esophagus - the Evolving Management of Extraesophageal Presentations of Gastroesophageal Reflux Disease
  http://www.medscape.com/viewarticle/418560

  (4) Gastrin
  http://en.wikipedia.org/wiki/Gastrin

  (5) Pepsin
  http://en.wikipedia.org/wiki/Pepsin

  (6) Sulfate and Sulfation
  http://www.epsomsaltcouncil.org/articles/Sulfation_Benefits_072204.pdf

  (7) Chapter 36: Digestion and Nutrition
  http://www.sirinet.net/~jgjohnso/apbio36.html

  (8) Digestion
  http://en.allexperts.com/e/d/di/digestion.htm

  (9) Digestive System
  http://www1.fccj.edu/sspring/digestion.htm

  (10) Improvement of analytical conditions of mineral Caco-2 cell uptake assays
  http://cat.inist.fr/?aModele=afficheN&cpsidt=15802597

  (11) Digestion in the Stomach
  http://www.loomisenzymes.com/articles.asp?article=4

  (12) Pancreas
  http://www.innvista.com/HEALTH/anatomy/pancreas.htm

  (13) Exocrine Secretions of the Pancreas
  http://arbl.cvmbs.colostate.edu/hbooks/pathphys/digestion/pancreas/exocrine.html

  (13) Carbonic Anhydrase
  http://arbl.cvmbs.colostate.edu/hbooks/pathphys/digestion/pancreas/carbonic_a...

  (14) Exocrine Secretions of the Pancreas
  http://biology.about.com/library/organs/bldigestpan2.htm

  (15) Carboxypeptidase
  http://en.wikipedia.org/wiki/Carboxypeptidase

  (16) 14. Anatomy of the Gastrointestinal Tract and Drug Absorption
  http://www.chemcases.com/pheno/pheno14.htm

  (17) Nanomedicine, Volume I: Basic Capabilities
  http://www.chemcases.com/pheno/pheno14.htm

  (18) The effects of zinc deficiency on pancreatic carboxypeptidase activity and protein digestion and absorption in the rat
  http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1270318&blobtype=pdf

  (19) Trypsin
  http://en.wikipedia.org/wiki/Trypsin

  (20) Chymotrypsin
  http://en.wikipedia.org/wiki/Chymorypsin

  (21) InterPro: IPR011163 Peptidase S1A, enteropeptidase
  (http://www.ebi.ac.uk/interpro/IEntry?ac=IPR011163

  (22) The Parietal Cell: Mechanism of Acid Secretion
  http://www.vivo.colostate.edu/hbooks/pathphys/digestion/stomach/parietal.html

  (23) Digestion
  http://en.wikipedia.org/wiki/Digestion

  (24) Small intestine
  http://en.wikipedia.org/wiki/Small_intestine

 
 
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