In Figure 1A/B each of the hormone amino acid residues is given a different color. The cholecystokinin (CCK) peptide hormone is colored blue and gastrin is colored green. The amino acid sequences of CCK and gastrin are presented in Figure 1A/B. A 115-amino-acid prepro form of cholecystokinin is cleaved to a 94 amino acid prohormone that is post-translationally transformed to peptide sizes 83, 58, 39, 33, 22, 8, and 5-amino-acid species. See Figure 1A/B. All of the biological activity of CCK is contained in the octopeptide (amino acids #52–#58), and it is likely that the other larger peptides represent intermediates in processing. In order to achieve full biological activity of CCK, the tyrosine at position 7 must be sulfated.

Fig1. Identification of the minimal amino acid sequences of cholecystokinin (CCK) and gastrin that are required for biological activity; and for gastrin, a clinical assessment of the size pattern of gastrin peptides required for biological activity in healthy subjects and patients with the Zollinger-Ellison syndrome. (A) Each of the amino acid residues for the CCK peptide hormone is colored blue, and for gastrin each amino acid residue is colored green. The CCK peptide and the gastrin peptides are aligned such that carboxy terminus amide of the phenylalanines are all aligned together. This result emphasizes that the final six amino acids of CCK, Gastrin-17, and Gastrin-34 are exactly identical and thus they are each colored orange. (B) The 101 amino acid progastrin is enzymatically processed into at least five major peptides that are shown in this panel. The three principal biologically active circulating forms are G34 (big gastrin), G17 (little gastrin), and G14 (mini-gastrin). Other low concentration gastrins include gastrin-6 (see the 6 gold colored residues of G-17 and G-34 in Panel A), and gastrin-52 and gastrin-71. (C and D) The relative amounts (fraction) of five blood circulating gastrin peptides are shown for healthy subjects and for comparison to patients with the Zollinger-Ellison syndrome (ZES). The suggestion is that the disease process associated with Zollinger-Ellison syndrome significantly changes the processing of the 101 amino acid precursor form of progastrin into the family of gastrin peptides. Data in panels C and D were abstracted from the following citation: J.R. Rehfeld et al., The Zollinger–Ellison Syndrome and mismeasurement of gastrin. Gastroenterology 140:1444–1445 (2011).

In order to identify regions of identical amino acid sequences for cholecystokinin (CKK) and gastrin and its various smaller fragments, the test peptides are aligned so that each of the carboxy-amide amino acid residues is directly even; see Figure 1A. By general convention for all peptides and proteins, the amino terminus is normally assigned position #1. Thus for CCK-58, gastrin-17, and gastrin-34, this alignment identifies that the position and ordering of the 5 amino acids starting with the carboxy-amidation of the three peptides are identical and have been colored gold. For CCK the minimum peptide with full biological activity has only 7 amino acids (see underlining braces); however, CCK peptides with 8, 33, or 58 residues (see labels on the peptide chain) are known to be present in vivo in the circulatory system, which suggests that they may have useful but not yet understood biological responses.

For gastrin, the three principal biologically active circulating forms are G34 (big gastrin), G17 (little gas trin), and G14 (mini-gastrin). Other low-concentration gastrins include gastrin-6 (see the six gold-colored residues of G-17 and G-34 in Figure 1A), gastrin-52, and gastrin-71. The minimum gastrin peptide with full bio logical activity has only 14 amino acids; in each instance the amino terminal residue is the #21 tryptrophan. For CCK, sulfation of the hydroxyl of tyrosine #52 is mandatory for biological activity; note that residue 52 is only 7 residues from the phenylalanine carboxyl-amidate terminus of the CCK. Both CCK and gastrin have an identical sequence for the last five residues ending with the carboxy-amidate. For the gastrins, sulfation of the #29 tyrosine is known to occur, but is not considered to be mandatory for full biological activity.

CCK, as determined by immunohistochemical techniques, is found principally in the duodenum and jejunum and also in the central nervous system (CNS), as well as in the nerves of the myenteric plexus of the intestine and the nerves of the urinary bladder and uterus.

The two major biological responses initiated by CCK are stimulation of the acinar cells of the pancreas to secrete pancreatic enzymes and stimulation of gallbladder contraction. The release of CCK from the endocrine cells in the intestinal mucosa is stimulated by the break down products of food in the duodenum, particularly 10-18-carbon fatty acids and L-amino acids.

The biological actions of CCK result as the consequence of interactions with two classes of receptors; the CCK-A receptor is predominantly present in the pancreas and gallbladder, while the CCK-B receptor is found in the central nervous system. There is some evidence that the occupancy of CCK receptors by CCK may contribute to a meal termination signal, i.e., to function as a satiety factor.

Both the CCK-A and CCK-B receptors are highly glycosylated. The CCK-B receptor has an amino acid sequence that is 48% identical to that of the CCK-A receptor. Both receptors contain the seven transmembrane domains characteristic of G protein-coupled receptors. In the pancreatic acinar cell, CCK stimulates amylase release via a complex signal transduction system involving IP3, nitric oxides, cGMP, and Ca2+ channels.

The bulk of gastrointestinal gastrin is localized within the G cells of the stomach antrum; the G-17 peptide form of gastrin predominates here. Gastrin has also been localized in the brain. The principal stimulants for gas trin release are partially digested proteins, peptides, and amino acids. Gastrin secretion can also be stimulated by vagus nerve stimulation and the condition of insulin hypoglycemia. Gastrin secretion is inhibited by antral acidification to pH ~1.0–2.5. Gastrin release is also stimulated by bombesin and inhibited by secretin, GIP, VIP, and somatostatin.

The principal biological action of gastrin is to stimulate the release of HCl by the parietal cells. These responses are achieved via direct interaction of gastrin with a cell-surface membrane receptor and via indirect stimulation of the release of histamine from enterochromaffin-like cells present in the gastric mucosa.

The disease known as Zollinger-Ellison syndrome (ZES) is characterized as an advanced ulcer proliferation of the upper gastrointestinal tract; see section IV.C at the end of this chapter. The ulcer interferes with the production and actions of gastrin. A study involving humans has been completed so that a clinical assessment of the size pattern of gastrin peptides present in healthy sub jects can be compared with the size pattern of patients with the Zollinger-Ellison syndrome. See Figure 1C/D. A postulate is that the disease process associated with the Zollinger-Ellison syndrome will make significant changes in the processing of the 101 amino acid precursor form of progastrin into the family of gastrin peptides. The gastrin peptides were isolated from the blood and separated on the basis of their size via column chromatography so that the relative amounts of the five gastrin peptides could be quantitated. As shown in Figure 1D, the subjects with ZES clearly have a different peptide fragment profile from that of the normal subjects (panel C). For patients with ZES, the proportion of gastrin-34 was increased from 38% (healthy control) to 58% (ZES patients). In contrast, gastrin 17 was decreased from 56% (healthy control) to 27% (ZES patients). This suggests that some aspect of the Zollinger-Ellison syndrome is capable of changing the size pattern of gastrin fragments.

اخر الاخبار

اخبار العتبة العباسية المقدسة

تستمر طيلة شهر رمضان.. إقامة ختمة قرآنية تعليمية في مقام الإمام المهدي (عجل الله فرجه)

في مستشفى الكفيل.. جراحة دقيقة بين الأذن والدماغ تنقذ مريضة من التهاب حاد

المجمع العلمي يُطلق مسابقة (فرسان التنزيل الفرقية الأولى) ويقيم ختمات قرآنية في محافظة المثنى

ضمن أنشطته الإنسانية.. قسم الشؤون الفكرية يفتتح البئر الـ 72 في نيجيريا

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الآخبار الصحية

دراسة تحذر من الإفراط في ممارسة الرياضة.. كيف يضر دماءك؟

الطهي بزيت الزيتون.. مضر أم مفيد؟

دماغ الرضع في خطر.. دراسة تحذر من "العدو الخفي"

التمر بالحليب عند الإفطار.. "كنز صحي" في رمضان

المزيد

الآخبار التكنلوجية

أثر نفسي غير متوقع للرياضة.. مرتبط بالغضب

القمر يواصل الانكماش.. رصد تشققات حديثة على سطحه

إطلاق أول تطبيق مراسلة "مشفّر".. ثورة في عالم الدردشة

خلل تقني يؤجّل أول رحلة مأهولة إلى القمر منذ عقود

المزيد

مواضيع ذات صلة

Problems of Food Processing and Digestion

General Principles of Gastrointestinal Motility

امتصاص نواتج الهضم الميكروبي

الهضم الميكروبي

أمتصاص الاملاح والماء

امتصاص الفيتامينات

هضم وامتصاص الأحماض النووية

هضم وامتصاص الدهون

هضم وامتصاص البروتين

هضم وامتصاص السكريات

هضم المكونات الغذائية

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