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999 (emergency telephone number)
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A sign on a beach in Whitstable, United Kingdom, advising readers to dial 999 in the event of an emergency.
999 is an official emergency telephone number in a number of countries which allows the caller to contact emergency services for urgent assistance.
Countries and territories using 999 include Bahrain, Bangladesh, Botswana, Ghana, Hong Kong, Kenya, Macau, Malaysia, Mauritius, Qatar, Ireland, Poland, Saudi Arabia, Singapore, Swaziland, Trinidad and Tobago, the United Arab Emirates, the United Kingdom, and Zimbabwe.
Contents
[hide]
1 United Kingdom
1.1 Emergency services
1.2 History
1.3 Procedure
1.4 Location
1.5 Abandoned and hoax calls
2 Ireland
3 Bangladesh
4 Hong Kong and Macau
5 Malaysia
6 Mauritius
7 Poland
8 United Arab Emirates
9 Singapore
10 Swaziland
11 Trinidad and Tobago
12 Others
13 See also
14 References
United Kingdom[edit]
999 is the official emergency number for the United Kingdom, but calls are also accepted on the European Union emergency number, 112. All calls are answered by 999 operators. Calls are always free.
Emergency services[edit]
Distribution of emergency calls between service ECCs in the United Kingdom (based on 2011 data).
In the United Kingdom there are four emergency services which maintain full-time Emergency Control Centres (ECC), to which 999 emergency calls may be directly routed by emergency operators in telephone company Operator Assistance Centres (OAC). These services are as follows, listed in the order of percentage of calls received:[1]
Police
Ambulance service
Fire Brigade
Coastguard
Other emergency services may also be reached through the 999 system, but do not maintain permanent Emergency Control Centres. All of these emergency services are summoned through the ECC of one of the four principal services listed above:
Lifeboat service
Mountain rescue service
Cave rescue service
Moorland search and rescue service (particularly in Cornwall and Yorkshire)
Quicksand search and rescue service (operating in the extensive quicksands of Morecambe Bay)[2]
Mine rescue service
Bomb disposal (provided by HM Armed Forces)
History[edit]
First introduced in the London area on 30 June 1937, the UK's 999 number is the world's oldest emergency call telephone service. The system was introduced following a fire on 10 November 1935 in a house on Wimpole Street in which five women were killed.[3] A neighbour had tried to telephone the fire brigade and was so outraged at being held in a queue by the Welbeck telephone exchange that he wrote a letter to the editor of The Times,[4] which prompted a government inquiry.[3]
The initial scheme covered a 12-mile radius around Oxford Circus[5] and the public were advised only to use it in ongoing emergency if "for instance, the man in the flat next to yours is murdering his wife or you have seen a heavily masked cat burglar peering round the stack pipe of the local bank building."[6] The first arrest – for burglary – took place a week later and the scheme was extended to major cities after World War II and then to the whole UK in 1976.[6]
The 9-9-9 format was chosen based on the 'button A' and 'button B' design of pre-payment coin-operated public payphones in wide use (first introduced in 1925) which could be easily modified to allow free use of the 9 digit on the rotary dial in addition to the 0 digit (then used to call the operator), without allowing free use of numbers involving other digits; other combinations of free call 9 and 0 were later used for more purposes, including multiples of 9 (to access exchanges before STD came into use) as a fail-safe for attempted emergency calls, e.g. 9 or 99, reaching at least an operator.[7]
Rotary phone dial
As it happens, the choice of 999 was fortunate for accessibility reasons, compared with e.g. lower numbers, because in the dark or in dense smoke 999 could be dialled by placing a finger one hole away from the dial stop (see the articles on rotary dial and GPO telephones) and rotating the dial to the full extent three times. This enables all users including the visually impaired to easily dial the emergency number. It is also the case that it is relatively easy for 111, and other low-number sequences, to be called accidentally, including when transmission wires making momentary contact produce a pulse similar to dialling (e.g. when overhead cables touch in high winds).[8][9]
Hoax calls and improper use are an issue. For these reasons, there are frequent public information campaigns in the UK on the correct use of the 999 system.
Alternative three-digit numbers for non-emergency calls have also been introduced in recent years. 101 was introduced for non-urgent calls in England and Wales[10] The scheme was extended to Scotland[11] and Northern Ireland.[12]
Trials of 111 as a number to access health services in the UK for urgent but not life-threatening cases began in England in 2010. The main roll-out occurred from 2011 to 2013, with a number of delays, and was completed by February 2014.[citation needed] In Scotland, the NHS24 service moved from 0845 424 2424 to 111 on 29 April 2014.[13][14] NHS Direct Wales continues to use 0845 46 47 despite it costing up to 57p per minute from mobile phones.
In 2008–2009, Nottinghamshire Police ran a successful pilot of Pegasus, a database containing the details of people with physical and learning disabilities or mental health problems, who have registered with the force because their disabilities make it difficult for them to give spoken details when calling the police. Those registered on the database are issued with a personal identification number (PIN) that can be used in two ways. By phone – either 999 or the force's non-emergency 101 number can be used – once a person is put through to the control room, they only need to say "Pegasus" and their PIN. Their details can then be retrieved from the database and the caller can quickly get on with explaining why they have called. In person – the Pegasus PIN can be told or shown to a police officer. Pegasus is also used by the City of London Police, Dyfed Powys Police, Surrey Police & Lincolnshire Police.
The introduction of push-button (landline, cordless and mobile) telephones has produced a problem for UK emergency services,[15] due to the ease of same-digit sequences being accidentally keyed, e.g., by objects in the same pocket as a telephone (termed 'pocket dialling') or by children playing with a telephone. This problem is less of a concern with emergency numbers that use two different digits, such as 112 and 911 although on landlines 112 suffers much of the same risk of false generation as the 111 code which was considered and rejected when the original choice of 999 was made.
The pan-European 112 code was introduced in the UK in April 1995[16] with little publicity. It connects to existing 999 circuits. The GSM standard mandates that the user of a GSM phone can dial 112 without unlocking the keypad, a feature that can save time in emergencies but that also causes some accidental calls. All mobile telephones will make emergency calls with the keypad locked. Originally a valid SIM card was not required to make a 999/112 emergency call in the UK. However, as a result of high numbers of untraceable hoax calls being made, this feature is now blocked by all UK networks. Most UK mobile telephone handsets will dial 999/112 without a SIM inserted (or with a locked/invalid SIM), but the call will not be connected. Following the blocking of SIM-less calls, in 2009 the UK networks introduced emergency call roaming. This allows a user with a valid SIM of a UK network to make emergency calls on any network for which they have coverage.
Silent solution 55 is the name given to the initiative that allows people to call 999 when they aren’t able to speak. If there is no answer, the operator will then ask you to cough, or make another audible sign that you’re in need of police assistance. If you’re in too much danger to make any sound at all, the call will be put through to an automated system which asks the caller to press 55 if they’re in danger.[17]
Procedure[edit]
999 or 112 is used to contact the emergency services upon witnessing or being involved in an emergency. In the United Kingdom, the numbers 999 and 112 both connect to the same service, and there is no priority or charge for either of them.
An emergency can be:
A person in immediate danger of injury or whose life is at risk
Suspicion that a crime is in progress, or that an offender is in the area
Structure on fire
Another serious incident which needs immediate emergency service attendance
All telecoms providers operating in the UK are obliged as part of their licence agreement to provide a free of charge emergency operator service. As of 2014 emergency calls made on any network in the UK are handled predominantly by BT, although other emergency operator services are provided by Vodafone (ex-Cable&Wireless) and Level 3 Communications (ex-Global Crossing, previously British Rail Telecoms).
On dialling 999 or 112 an operator will answer and ask, "Emergency. Which service?"[18] Previously operators asked "Which service do you require?" (approximately up to the mid-90s).
The operator will then transfer the call to the appropriate service's own call-taker. If the caller is unsure as to which service they require, the operator will default the call to the police, and if an incident requires more than one service, for instance a road traffic accident with injuries and trapped people, depending on the service the caller has chosen, this service will alert the other services for the caller (while the operator has to also contact each emergency service individually, regardless of whether the caller has remained on the line). The caller will be connected to the service which covers the area that they are (or appear to be) calling from.
On 6 October 1998, BT introduced a new system whereby all the information about the location of the calling telephone was transmitted electronically to the relevant service rather than having to read it out (with the possibility of errors). This system is called EISEC (Enhanced Information Service for Emergency Calls). Previously, the operator had to start the connection to the emergency service control room by stating the location of the operator, followed by the caller's telephone number, e.g. "Bangor connecting 01248 300 000". It was common for the person calling to be confused as to why the operator was talking to the emergency service, and the caller frequently talked over the operator. Only around 50% of the emergency authorities have EISEC, although the number is ever increasing, so, in those cases without EISEC present, the operator still has to pass their location and the caller's number.
The rooms in which operators work are called operator assistance centres (OACs). There are BT OACs in Bangor, Blackburn, Dundee, Glasgow, Liverpool, Newport, and Nottingham. The rooms in which emergency response operators work are called Emergency Control Centres (ECCs) and are operated by local authorities.
In some situations there may be specific instructions on nearby signs to notify some other authority of an emergency before calling 999. For example, bridges carrying railways over roads may carry signs advising that if a road vehicle strikes the bridge the railway authority (Network Rail in most instances) (on a given number) should be called first to alert the railway operator of the potential of a major incident occurring should a train pass over the damaged bridge. Network Rail has its own procedures to alert trains to the emergency and to stop them if necessary. The instructions on the signs then state 999 should then be dialled and that the Police should be requested.
Access to the 999/112 service is provided for the hearing-impaired via Textphone and use of the Text Relay service, run by BT to cover all telephone providers, and previously known as the RNID "Typetalk" relay service. The number is 18000.
999 is also accessible via SMS for pre-registered users.[a] The service is open for anyone to register and works with all major providers in the UK.[19]
Location[edit]
It is important for the caller to be aware of their location when phoning for the emergency services; the caller's location will not be passed onto the emergency services immediately, and finding the location requires a combination of efforts from both parties. However it is possible to trace both landline and mobile telephone numbers with the BT operator; the former can be traced to an address. The latter can be immediately traced to a grid reference according to the transmitter being used,[20] however this is only accurate to a certain wide area — for more specific traces senior authority must be acquired and an expensive operation can be conducted to trace the mobile phone to within a few metres. A number of smartphone apps can now be downloaded that assist with caller location by using the smartphone's satellite navigation features.
Since 2014, smartphones will detect that an emergency call is being placed, and use any available location services (WiFi or GPS based location) to send an emergency SMS which also contains an identifier for the call. This is intended to be received by the mobile operator whilst the call is in progress.[21]
On some occasions callers will be put through to the wrong area service – this is called a "misrouted nines". The most common reason for this is when a mobile phone calls 999 and is using a radio transmitter that is located in another force area; most frequently these are calls that are made within a few miles of a border. Upon establishing the incident location, the emergency service operator will relay the information to the responsible force for their dispatch. In most areas, other forces will respond to incidents just within the border if they could get there quicker, assist, and then hand over to the other force when they arrive.
In the United Kingdom the Highways Agency have placed blue signs with the location printed on them, at approximately 500-metre intervals on their managed routes, such as motorways and major A-Roads. These signs contain a code which can be given to the emergency operator to locate you quickly. For example, a sign may say "M1 A 100.1". This translates as the M1 motorway, on the "Alpha" carriageway, at 100.1 kilometres from its start (or nominal start). The "Alpha" and "Bravo" carriageways are designated by the Highways Agency to each side of the road, dependent upon which direction it travels; other letters are used for additional carriageways at intersections. These signs are in addition to the pre-existing 100m distance marker posts alongside the carriageway.
Abandoned and hoax calls[edit]
This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (March 2013) (Learn how and when to remove this template message)
[22]An abandoned call is when a caller, intentionally or otherwise, rings 999 and then ends the call or stays silent; this could be for any number of reasons, including coercion or harm coming to the caller. Abandoned calls are filtered by emergency operators BT and Cable & Wireless which they are either disconnected or passed on to police.
They are normally disconnected by the operator repeating "Emergency. Which service?", then if no response is given, the operator will say "Do you need police, fire or ambulance?". If there is still no response, the operator will sometimes ask the caller to press the keypad or make a noise if they need assistance. If no response is given, they will confirm they are clearing the line.
For abandoned calls, if the caller requests the police and the call is routed to police and then the line is dropped, either while waiting for connection or on the line with police, they are checked by police and a call back will be done. If there is no answer, the police service are likely to attend and if the line is disconnected without the caller telling the operator which service they need, they then make a decision to filter the call to police (if suspicious background noise) or clear the line.
The most common reasons for abandoned calls include:
Accidental dialling of 999 on mobile phones. As a GSM standard, mobile phones still allow emergency calls to be made even with the keypad locked.
Faulty phone lines.
Believing an urban myth that says dialing 999 charges mobile phone batteries
Ireland[edit]
In Ireland, 999 (and the European and GSM standard 112)[23] are the national emergency numbers. The 999 and 112 service is able to respond in English, Irish[citation needed], Polish, French, German and Italian. 999 and 112 operators in Ireland answer the calls in under one second and say "Emergency, which service?". The caller may then request the Gardaí (the Irish police), ambulance, fire brigade, coastguard, or cave and mountain rescue service. The caller is then transferred to the emergency dispatcher for the appropriate service.[24]
Bangladesh[edit]
In Bangladesh, 999 is the emergency number.It's available for Dhaka And Chittagong only. History “This helpdesk number is toll-free,” according to an allotment letter signed by BTRC Deputy Director Md Mesbahuzzaman on September 5.
Previously allotted short codes 2041 and 16666 for the help desk were cancelled by the regulators, the letter said.
In the letter, BTRC said that short code 999 was allocated to the ICT Division to run its national help desk and it will be free of charge.
The services will be provided under the national help desk, which is being set up at a cost of Tk 60.50 crore. The help desk will be rolled out shortly, according to officials of the ICT division.
The telecommunication regulator initially allotted 2041 and 16666 short codes for the help desk, but upon ICT State Minister's Zunaid Ahmed Palak's request the second code was changed to a three-digit one.
At present, dialling 100 would connect to Bangladesh Police, 101 to Rapid Action Battalion, 102 to fire services, 103 to ambulance service and 104 to the Access to Information Programme under the Prime Minister's Office.
Currently, the ICT division runs a customer complaint centre on the 16364 short code. Earlier, State Minister for Telecom Tarana Halim said she planned to bring all the emergency services under a simple three-digit short code.
Hong Kong and Macau[edit]
999 was introduced to Hong Kong for emergency services (Police，Fire-fighting Services and Ambulance Services) during British rule and continues to be used following the transfer of sovereignty.
Macau also adopted the 999 number; it also introduced two emergency hotline numbers: 110 (mainly for tourists from mainland China) and 112 (mainly for tourists from overseas).
The worldwide emergency number for GSM mobile phones, 112, also works on all GSM networks in the country. Calls made to this number are redirected to the 999 call centre.
Malaysia[edit]
The 999 emergency services in Malaysia is staffed by about 138 telephonists from Telekom Malaysia. Like Singapore, the number was inherited from British rule and continued after independence. Ongoing upgrading works are taking place to introduce the Computer-Telephony Integration (CTI) for hospital exchanges, digital mapping to track the callers' locations and Computer Assisted Despatching (CAD) for online connectivity among the agencies providing the emergency services in the country. All calls to the number are made free of charge. In the late 90s, the number 994 was adopted as a direct connection to fire stations, but use of the number has been discontinued due to cost-saving measures taken by the government. 991 Connects to civil services.
The worldwide emergency number for GSM mobile phones, 112, also works on all GSM networks in the country. Calls made to this number are redirected to the 999 call centre.
Mauritius[edit]
Mauritius uses the 999 emergency number for police contact only. The other emergency numbers in use are 114 for emergency medical assistance and 115 for the fire service.[25]
Poland[edit]
The 112 emergency number is an all-service number in Poland like in other EU states, but old numbers that were traditionally designated for emergencies are still in use parallel to 112. Those are 999 for ambulance, 998 for fire brigade and 997 for police.
United Arab Emirates[edit]
In the United Arab Emirates the 999 service is used to contact the police who are also capable of forwarding the call as appropriate to the ambulance or fire services. The number 998 connects directly to the ambulance service and 997 to the fire brigade.
Singapore[edit]
In Singapore, the number 999 was inherited from British rule and continued after independence. The number is attributed more to requesting for the police, with the number 995, established in 1984, used for direct lines to the fire brigade and ambulance services of the Singapore Civil Defence Force. Because most of the population of Singapore is Chinese, it is likely that 995 was adopted because the Chinese pronunciation for that number (jiŭ jiŭ wŭ) sounds similar to the Chinese phrase for 'Save me' (jiù jiù wŏ).
Swaziland[edit]
The Kingdom of Swaziland uses the 999 emergency number for police contact only. Also 975 for human trafficking reports. The other emergency numbers in use are 977 for emergency medical assistance and 933 for the fire service.
Trinidad and Tobago[edit]
In Trinidad and Tobago, 999 is used to contact the police only. The number 990 is used for the ambulance service and fire brigade.
Others[edit]
In 1959, Winnipeg, Manitoba (16 municipalities) used 9-9-9[26] as the first North American deployment of a local unified emergency number.[27] North America later standardised on 9-1-1, with +1-204-999-xxxx eventually reassigned as a standard mobile telephone exchange.[28]
See also[edit]
Look up 999 in Wiktionary, the free dictionary.
000 – emergency number in Australia
111 – emergency number in New Zealand
112 – emergency number across the European Union and on GSM mobile networks across the world
119 – emergency number in Jamaica and parts of Asia
9-1-1 (also known as 911) – emergency number in Canada, the Cayman Islands, and the United States
999 (disambiguation)
eCall
Emergency Control Centre
Emergency telephone
Emergency telephone number
In case of emergency
Police 101 - non-emergency number for contacting the police in England, Northern Ireland, Scotland, and Wales
Single Non-Emergency Number
References[edit]
Jump up ^ Data from British Telecom, based on the year 2011, and available on-line here [1].
Jump up ^ Service details here [2].
^ Jump up to: a b The Times (9 September 2009). "999: can somebody help? It's an emergency". London. Retrieved 2009-09-11.
Jump up ^ The Times (11 November 1935). "The fire in Wimpole Street". London. Retrieved 2009-09-11.
Jump up ^ Gary Holland (13 May 2010). "Why 999 for an emergency?". BBC History. Retrieved 1 July 2012.
^ Jump up to: a b Keith Moore (30 June 2012). "Dial 999: 75 years of emergency phone calls". BBC News.
Jump up ^ Atkinson (1950). Telephony, Volume 2. Pitman.
Jump up ^ BT plc (29 June 2007). "999 celebrates its 70th birthday". Archived from the original on 2009-03-02. Retrieved 2009-03-02.
Jump up ^ BBC (26 November 2008). "When are silent 999 calls cut off?". BBC News. Archived from the original on 3 December 2008. Retrieved 2008-11-26.
Jump up ^ "Welcome to 101". Home Office.
Jump up ^ "101". Police Scotland.
Jump up ^ "New 101 number for non-emergency PSNI calls". BBC News. BBC. 2014-03-14.
Jump up ^ "New 111 telephone number". NHS 24. 2014-04-29. Archived from the original on 2014-04-29.
Jump up ^ "New 111 freephone number for NHS 24 helpline". BBC News. 2014-04-29. Archived from the original on 2014-04-29.
Jump up ^ BBC News Online (21 March 2000). "Mobiles blamed for emergency calls". Retrieved 2008-01-12.
Jump up ^ Oftel (May 2000), Access Codes: Options for the future, retrieved 2012-07-31
Jump up ^ "Silent 999 Calls | West Yorkshire Police". www.westyorkshire.police.uk. Retrieved 2017-06-06.
Jump up ^ Service, London Ambulance (2013-07-08). "What happens when you call 999". www.londonambulance.nhs.uk. Retrieved 2016-03-23.
Jump up ^ "Questions and answers | EmergencySMS". www.emergencysms.org.uk/. Retrieved 22 February 2017.
Jump up ^ Ofcom (15 January 2004). "Enhanced 999 facility for mobile phones". Retrieved 7 June 2012.
Jump up ^ "Location information for emergency calls from mobile phones" (PDF). Ofcom.
Jump up ^ "Silent 999 Calls". www.herts.police.uk. Retrieved 2017-06-01.
Jump up ^ "Archived copy". Archived from the original on 18 February 2011. Retrieved 2011-02-22. 112 Official Website
Jump up ^ "RTÉ News (11 February 2009)". RTÉ.ie. 11 February 2009.
Jump up ^ Mauritius Country Specific Information Archived 4 August 2011 at the Wayback Machine., U.S. Department of State, 18 January 2011.
Jump up ^ http://www.winnipeg.ca/police/History/history5.stm
Jump up ^ http://www.cbc.ca/archives/entry/winnipeggers-call-999-for-help
Jump up ^ http://www.localcallingguide.com/lca_prefix.php?npa=204&nxx=999
Jump up ^ www.emergencySMS.org.uk Official website
[hide]
v
t
e
Emergency telephone numbers
000 (Australia)
108 (India)
110 (Iran; Police)
111 (New Zealand)
1122 (Pakistan)
112 (EU and various others)
119 (parts of Asia and Jamaica)
120 (China)
911 (North America E-911 system, Philippines)
999 (UK and various others)
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Pepsin
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pepsin C (gastricsin)
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3.4.23.3
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9012-71-9
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Pepsin is an endopeptidase that breaks down proteins into smaller peptides (that is, a protease). It is produced in the stomach and is one of the main digestive enzymes in the digestive systems of humans and many other animals, where it helps digest the proteins in food. Pepsin has a three dimensional structure, of which one or more polypeptide chains twist and fold, bringing together a small number of amino acids to form the active site, or the location on the enzyme where the substrate binds and the reaction takes place. Pepsin is an aspartic protease, using a catalytic aspartate in its active site [2].
It is one of three principal proteases in the human digestive system, the other two being chymotrypsin and trypsin. During the process of digestion, these enzymes, each of which is specialized in severing links between particular types of amino acids, collaborate to break down dietary proteins into their components, i.e., peptides and amino acids, which can be readily absorbed by the small intestine. Pepsin is most efficient in cleaving peptide bonds between hydrophobic and preferably aromatic amino acids such as phenylalanine, tryptophan, and tyrosine.[3]
Pepsin's proenzyme, pepsinogen, is released by the chief cells in the stomach wall, and upon mixing with the hydrochloric acid of the gastric juice, pepsinogen activates to become pepsin.[2]
Contents
[hide]
1 History
2 Precursor
3 Activity and stability
4 In laryngopharyngeal reflux
5 Storage
6 Inhibitors
7 Applications
8 Genes
9 References
10 External links
History[edit]
Pepsin was one of the first enzymes to be discovered. It was discovered in 1836 by Theodor Schwann. Schwann coined its name from the Greek word πέψις pepsis, meaning "digestion" (from πέπτειν peptein "to digest").[4][5][6][7] Scientists around this time began discovering many biochemical compounds that play a significant role in biological processes, and pepsin was one of them. An acidic substance that was able to convert nitrogen-based foods into water-soluble material was determined to be pepsin.[8]
In 1928, it became one of the first enzymes to be crystallized when John H. Northrop crystallized it using dialysis, filtration, and cooling.[9]
Precursor[edit]
Pepsin is expressed as a zymogen called pepsinogen, whose primary structure has an additional 44 amino acids.
In the stomach, chief cells release pepsinogen. This zymogen is activated by hydrochloric acid (HCl), which is released from parietal cells in the stomach lining. The hormone gastrin and the vagus nerve trigger the release of both pepsinogen and HCl from the stomach lining when food is ingested. Hydrochloric acid creates an acidic environment, which allows pepsinogen to unfold and cleave itself in an autocatalytic fashion, thereby generating pepsin (the active form). Pepsin cleaves the 44 amino acids from pepsinogen to create more pepsin.
Activity and stability[edit]
Pepsin is most active in acidic environments between 37 °C and 42 °C.[10][11] Accordingly, its primary site of synthesis and activity is in the stomach (pH 1.5 to 2). Pepsin will digest up to 20% of ingested amide bonds by cleaving preferentially at the N-terminal side[12]:96 of aromatic amino acids such as phenylalanine, tryptophan, and tyrosine.[12]:675 Pepsin exhibits preferential cleavage for hydrophobic, preferably aromatic, residues in P1 and P1' positions. Increased susceptibility to hydrolysis occurs if there is a sulfur-containing amino acid close to the peptide bond, which has an aromatic amino acid. Pepsin cleaves Phe1Val, Gln4His, Glu13Ala, Ala14Leu, Leu15Tyr, Tyr16Leu, Gly23Phe, Phe24 in the insulin B chain. Pepsin exhibits maximal activity at pH 2.0 and is inactive at pH 6.5 and above, however pepsin is not fully denatured or irreversibly inactivated until pH 8.0.[13] Therefore, pepsin in solution of up to pH 8.0 can be reactivated upon re-acidification. The stability of pepsin at high pH has significant implications on disease attributed to laryngopharyngeal reflux. Pepsin remains in the larynx following a gastric reflux event.[14][15] At the mean pH of the laryngopharynx (pH = 6.8) pepsin would be inactive but could be reactivated upon subsequent acid reflux events resulting in damage to local tissues.
In laryngopharyngeal reflux[edit]
Pepsin is one of the primary causes of mucosal damage during laryngopharyngeal reflux.[16][17] Pepsin remains in the larynx (pH 6.8) following a gastric reflux event.[14][15] While enzymatically inactive in this environment, pepsin would remain stable and could be reactivated upon subsequent acid reflux events.[13] Exposure of laryngeal mucosa to enzymatically active pepsin, but not irreversibly inactivated pepsin or acid, results in reduced expression of protective proteins and thereby increases laryngeal susceptibility to damage.[13][14][15]
Pepsin may also cause mucosal damage during weakly acidic or non-acid gastric reflux. Weak or non-acid reflux is correlated with reflux symptoms and mucosal injury.[18][19][20][21] Under non-acid conditions (neutral pH), pepsin is internalized by cells of the upper airways such as the larynx and hypopharynx by a process known as receptor-mediated endocytosis.[22] The receptor by which pepsin is endocytosed is currently unknown. Upon cellular uptake, pepsin is stored in intracellular vesicles of low pH at which its enzymatic activity would be restored. Pepsin is retained within the cell for up to 24 hours.[23] Such exposure to pepsin at neutral pH and endoyctosis of pepsin causes changes in gene expression associated with inflammation, which underlies signs and symptoms of reflux,[24] and tumor progression.[25] This and other research[26] implicates pepsin in carcinogenesis attributed to gastric reflux.
Pepsin in airway specimens is considered to be a sensitive and specific marker for laryngopharyngeal reflux.[27][28] Research to develop new pepsin-targeted therapeutic and diagnostic tools for gastric reflux is ongoing. A rapid non-invasive pepsin diagnostic called Peptest is now available which determines the presence of pepsin in saliva samples.[29]
Storage[edit]
Pepsins should be stored at very low temperatures (between −80 °C and −20 °C) to prevent autolysis (self-digestion).
Inhibitors[edit]
Pepsin may be inhibited by high pH (see "Activity" and "Stability", above) or by inhibitor compounds. Pepstatin is a low molecular weight compound and potent inhibitor specific for acid proteases with a Ki of about 10−10 M for pepsin. The statyl residue of pepstatin is thought to be responsible for pepstatin inhibition of pepsin; statine is a potential analog of the transition state for catalysis by pepsin and other acid proteases. Pepstatin does not covalently bind pepsin and inhibition of pepsin by pepstatin is therefore reversible.[30] 1-bis(diazoacetyl)-2-phenylethane reversibly inactivates pepsin at pH 5, a reaction which is accelerated by the presence of Cu(II).[31]
Pepsin also undergoes feedback inhibition; a product of protein digestion slows down the reaction by inhibiting pepsin.[32][33]
Sucralfate also inhibits pepsin activity.
Applications[edit]
Commercial pepsin is extracted from the glandular layer of hog stomachs. It is a component of rennet used to curdle milk during the manufacture of cheese. Pepsin is used for a variety of applications in food manufacturing: to modify and provide whipping qualities to soy protein and gelatin,[34] to modify vegetable proteins for use in nondairy snack items, to make precooked cereals into instant hot cereals,[35] and to prepare animal and vegetable protein hydrolysates for use in flavoring foods and beverages. It is used in the leather industry to remove hair and residual tissue from hides and in the recovery of silver from discarded photographic films by digesting the gelatin layer that holds the silver.[36] Pepsin was historically an additive of Beemans gum brand chewing gum by Dr. Edward E. Beeman.
Pepsin is commonly used in the preparation of F(ab')2 fragments from antibodies. In some assays, it is preferable to use only the antigen-binding (Fab) portion of the antibody. For these applications, antibodies may be enzymatically digested to produce either an Fab or an F(ab')2 fragment of the antibody. To produce an F(ab')2 fragment, IgG is digested with pepsin, which cleaves the heavy chains near the hinge region.[37] One or more of the disulfide bonds that join the heavy chains in the hinge region are preserved, so the two Fab regions of the antibody remain joined together, yielding a divalent molecule (containing two antibody binding sites), hence the designation F(ab')2. The light chains remain intact and attached to the heavy chain. The Fc fragment is digested into small peptides. Fab fragments are generated by cleavage of IgG with papain instead of pepsin. Papain cleaves IgG above the hinge region containing the disulfide bonds that join the heavy chains, but below the site of the disulfide bond between the light chain and heavy chain. This generates two separate monovalent (containing a single antibody binding site) Fab fragments and an intact Fc fragment. The fragments can be purified by gel filtration, ion exchange, or affinity chromatography.[38]
Fab and F(ab')2 antibody fragments are used in assay systems where the presence of the Fc region may cause problems. In tissues such as lymph nodes or spleen, or in peripheral blood preparations, cells with Fc receptors (macrophages, monocytes, B lymphocytes, and natural killer cells) are present which can bind the Fc region of intact antibodies, causing background staining in areas that do not contain the target antigen. Use of F(ab')2 or Fab fragments ensures that the antibodies are binding to the antigen and not Fc receptors. These fragments may also be desirable for staining cell preparations in the presence of plasma, because they are not able to bind complement, which could lyse the cells. F(ab')2, and to a greater extent Fab, fragments allow more exact localization of the target antigen, i.e., in staining tissue for electron microscopy. The divalency of the F(ab')2 fragment enables it to cross-link antigens, allowing use for precipitation assays, cellular aggregation via surface antigens, or rosetting assays.[39]
Genes[edit]
The following three genes encode identical human pepsinogen A enzymes:
pepsinogen 3, group I (pepsinogen A)
Identifiers
Symbol
PGA3
Entrez
643834
HUGO
8885
OMIM
169710
RefSeq
NM_001079807
UniProt
P00790
Other data
EC number
3.4.23.1
Locus
Chr. 11 q13
pepsinogen 4, group I (pepsinogen A)
Identifiers
Symbol
PGA4
Entrez
643847
HUGO
8886
OMIM
169720
RefSeq
NM_001079808
UniProt
P00790
Other data
EC number
3.4.23.1
Locus
Chr. 11 q13
pepsinogen 5, group I (pepsinogen A)
Identifiers
Symbol
PGA5
Entrez
5222
HUGO
8887
OMIM
169730
RefSeq
NM_014224
UniProt
P00790
Other data
EC number
3.4.23.1
Locus
Chr. 11 q13
A fourth human gene encodes gastricsin also known as pepsinogen C:
progastricsin
(pepsinogen C)
Identifiers
Symbol
PGC
Entrez
5225
HUGO
8890
OMIM
169740
RefSeq
NM_001166424
UniProt
P20142
Other data
EC number
3.4.23.3
Locus
Chr. 6 pter-p21.1
References[edit]
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^ Jump up to: a b "Enzyme entry 3.4.23.1". Retrieved 2008-12-14.
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Jump up ^ Asimov I (1980). "page 95". A short history of biology. Westport, Conn: Greenwood Press. ISBN 0-313-22583-4.
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Jump up ^ πέψις, πέπτειν. Liddell, Henry George; Scott, Robert; A Greek–English Lexicon at the Perseus Project.
Jump up ^ Fruton JS (Jun 2002). "A history of pepsin and related enzymes". The Quarterly Review of Biology. 77 (2): 127–47. doi:10.1086/340729. JSTOR 3071644. PMID 12089768.
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Jump up ^ "Effects of pH". Retrieved 2010-04-29.
Jump up ^ "Information on EC 3.4.23.1 - pepsin A". Brenda-enzymes. Retrieved 2008-12-14.
^ Jump up to: a b Cox M, Nelson DR, Lehninger AL (2008). Lehninger principles of biochemistry. San Francisco: W.H. Freeman. ISBN 0-7167-7108-X.
^ Jump up to: a b c Johnston N, Dettmar PW, Bishwokarma B, Lively MO, Koufman JA (Jun 2007). "Activity/stability of human pepsin: implications for reflux attributed laryngeal disease". The Laryngoscope. 117 (6): 1036–9. doi:10.1097/MLG.0b013e31804154c3. PMID 17417109.
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^ Jump up to: a b c Johnston N, Dettmar PW, Lively MO, Postma GN, Belafsky PC, Birchall M, Koufman JA (Jan 2006). "Effect of pepsin on laryngeal stress protein (Sep70, Sep53, and Hsp70) response: role in laryngopharyngeal reflux disease". The Annals of Otology, Rhinology, and Laryngology. 115 (1): 47–58. doi:10.1177/000348940611500108. PMID 16466100.
Jump up ^ Goldberg HI, Dodds WJ, Gee S, Montgomery C, Zboralske FF (Feb 1969). "Role of acid and pepsin in acute experimental esophagitis". Gastroenterology. 56 (2): 223–30. PMID 4884956.
Jump up ^ Lillemoe KD, Johnson LF, Harmon JW (Aug 1982). "Role of the components of the gastroduodenal contents in experimental acid esophagitis". Surgery. 92 (2): 276–84. PMID 6808683.
Jump up ^ Tamhankar AP, Peters JH, Portale G, Hsieh CC, Hagen JA, Bremner CG, DeMeester TR (Nov 2004). "Omeprazole does not reduce gastroesophageal reflux: new insights using multichannel intraluminal impedance technology". Journal of Gastrointestinal Surgery. 8 (7): 890–7; discussion 897–8. doi:10.1016/j.gassur.2004.08.001. PMID 15531244.
Jump up ^ Kawamura O, Aslam M, Rittmann T, Hofmann C, Shaker R (Jun 2004). "Physical and pH properties of gastroesophagopharyngeal refluxate: a 24-hour simultaneous ambulatory impedance and pH monitoring study". The American Journal of Gastroenterology. 99 (6): 1000–10. doi:10.1111/j.1572-0241.2004.30349.x. PMID 15180717.
Jump up ^ Oelschlager BK, Quiroga E, Isch JA, et al. Gastroesophageal and pharyngeal reflux detection using impedance and 24-hour pH monitoring in asymptomatic subjects: defining the normal environment. J Gastrointest Surg 2006;10:54–62.
Jump up ^ Mainie I, Tutuian R, Shay S, Vela M, Zhang X, Sifrim D, Castell DO (Oct 2006). "Acid and non-acid reflux in patients with persistent symptoms despite acid suppressive therapy: a multicentre study using combined ambulatory impedance-pH monitoring". Gut. 55 (10): 1398–402. doi:10.1136/gut.2005.087668. PMC 1856433  . PMID 16556669.
Jump up ^ Johnston N, Wells CW, Blumin JH, Toohill RJ, Merati AL (Dec 2007). "Receptor-mediated uptake of pepsin by laryngeal epithelial cells". The Annals of Otology, Rhinology, and Laryngology. 116 (12): 934–8. doi:10.1177/000348940711601211. PMID 18217514.
Jump up ^ Johnston N, Wells CW, Samuels TL, Blumin JH (Aug 2010). "Rationale for targeting pepsin in the treatment of reflux disease". The Annals of Otology, Rhinology, and Laryngology. 119 (8): 547–58. doi:10.1177/000348941011900808. PMID 20860281.
Jump up ^ Samuels TL, Johnston N (Nov 2009). "Pepsin as a causal agent of inflammation during nonacidic reflux". Otolaryngology--Head and Neck Surgery. 141 (5): 559–63. doi:10.1016/j.otohns.2009.08.022. PMID 19861190.
Jump up ^ Balkwill F, Mantovani A (Feb 2001). "Inflammation and cancer: back to Virchow?". Lancet. 357 (9255): 539–45. doi:10.1016/S0140-6736(00)04046-0. PMID 11229684.
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Jump up ^ Knight J, Lively MO, Johnston N, Dettmar PW, Koufman JA (Aug 2005). "Sensitive pepsin immunoassay for detection of laryngopharyngeal reflux". The Laryngoscope. 115 (8): 1473–8. doi:10.1097/01.mlg.0000172043.51871.d9. PMID 16094128.
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Jump up ^ Bardhan KD, Strugala V, Dettmar PW (2012). "Reflux revisited: advancing the role of pepsin". International Journal of Otolaryngology. 2012: 1. doi:10.1155/2012/646901. PMC 3216344  . PMID 22242022.
Jump up ^ Marciniszyn J, Hartsuck JA, Tang J (1977). "Pepstatin inhibition mechanism". Advances in Experimental Medicine and Biology. 95: 199–210. doi:10.1007/978-1-4757-0719-9_12. PMID 339690.
Jump up ^ Husain SS, Ferguson JB, Fruton JS (Nov 1971). "Bifunctional inhibitors of pepsin". Proceedings of the National Academy of Sciences of the United States of America. 68 (11): 2765–8. Bibcode:1971PNAS...68.2765H. doi:10.1073/pnas.68.11.2765. PMC 389520  . PMID 4941985.
Jump up ^ Northrop HJ (1932). "The story of the isolation of crystalline pepsin and trypsin". The Scientific Monthly. 35 (4): 333–340. Bibcode:1932SciMo..35..333N.
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Jump up ^ Kun LY (2006). Microbial Biotechnology: Principles And Applications. World Scientific Publishing Company. ISBN 981-256-677-5.
Jump up ^ US patent 2259543, Billings HJ, "Fortified Cereal", published 1938, assigned to Cream of Wheat Corporation
Jump up ^ Smith ER (Sep 1933). "Gelatinase and the gates-gilman-cowgill method of pepsin estimation". The Journal of General Physiology. 17 (1): 35–40. doi:10.1085/jgp.17.1.35. PMC 2141270  . PMID 19872760.
Jump up ^ Falkenburg WJ, van Schaardenburg D, Ooijevaar-de Heer P, Tsang-A-Sjoe MW, Bultink IE, Voskuyl AE, Bentlage AE, Vidarsson G, Wolbink G, Rispens T (2016). "Anti-Hinge Antibodies Recognize IgG Subclass- and Protease-Restricted Neoepitopes". Journal of Immunology. doi:10.4049/jimmunol.1601096. PMID 27864476.
Jump up ^ Lane DS, Harlow E (1988). Antibodies: a laboratory manual. Cold Spring Harbor, N.Y: Cold Spring Harbor Laboratory. pp. A2926. ISBN 0-87969-314-2.
Jump up ^ "Enzyme Explorer- Pepsin". Sigma-Aldrich.
External links[edit]
The MEROPS online database for peptidases and their inhibitors: Pepsin A A01.001, Pepsin B A01.002, Pepsin C (Gastricsin) A01.003
Pepsin A at the US National Library of Medicine Medical Subject Headings (MeSH)
Pepsinogens at the US National Library of Medicine Medical Subject Headings (MeSH)
Pepsinogen A at the US National Library of Medicine Medical Subject Headings (MeSH)
Pepsinogen C at the US National Library of Medicine Medical Subject Headings (MeSH)
Beemans Gum
Pepsin: Molecule of the Month, by David Goodsell, RCSB Protein Data Bank
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text:
Charitie Lees Smith
From Wikipedia, the free encyclopedia
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Charitie Lees Smith
Born
21 June 1841
Bloomfield, Merrion, County Dublin, Ireland
Died
June 20, 1923(1923-06-20) (aged 81)
Oakland, California, US
Occupation
hymnwriter, religious writer
Language
English
Nationality
Ireland
Spouse
Arthur E. Bancroft (m. 1869),
Charitie Lees Smith (later, Charitie Lees Bancroft; still later Charitie de Cheney or Charitie de Chenez; pen name, C.L.S.[1] 21 June 1841 – 20 June 1923) was an Anglican Irish American hymnwriter. Her hymns, well known in England and Ireland, were included in Lyra Sacra Hibernica, Ryle's Spiritual Songs, Lyra Britannica, and Times of Refreshing.[2] Additionally, she wrote various religious pieces for periodicals.[3]
Contents
1 Early years
2 Career
3 Personal life
4 References
4.1 Attribution
4.2 Bibliography
5 Further reading
6 External links
Early years[edit]
Charitie Lees Smith was born on 21 June 1841, at Bloomfield, Merrion, County Dublin,[2] the fourth child of Rev. George Sidney Smith and Charlotte Lees.[4][3] The Rev. Smith was the minister of Colebrooke church, in the Church of Ireland parish of Aghalurcher from 1838–1867 and, during this period, the family lived in Ardunshin House near Brookeborough, County Fermanagh, Ireland.
Her talent for poetic composition was developed at an early period of her life.[4]
Career[edit]
In 1860, one of Smith's first compositions O for the robes of whiteness appeared in leaflet form in the immediate aftermath of the Irish 1859 revival. In 1863, she wrote perhaps her best known hymn "Before the Throne of God Above" which she entitled The Advocate (a hymn which was revived in evangelical circles in the late 20th century). In 1867, Smith's father took the family to Tattyreagh, Omagh, County Tyrone, when he became the rector of St Columba's Church. Smith continued with her compositions, publishing them in a volume entitled Within the Veil in 1867.
She wrote considerably for several serial publications and contributed hymns to J. C. Ryle's Spiritual Songs, Times of Refreshing, and Charles Rogers' Lyra Britannica (1866).[3] Her hymn, "Christ Mighty to Save," was included in the latter publication,[4] while "Heavenly Anticipations" was a favorite in Sunday schools.[5] "Mighty to Save" first appeared in 1867 in the Lyra Britannica, its form being seven stanzas of eight lines each, but it was considerably abbreviated to fit it for common use, including a cento beginning with the third verse.[6] "Aspirations" was written in the flush and fervor of coming "out of darkness into marvellous light" during the awakenings of 1859-60 in Ireland.[7]
Personal life[edit]
In 1869, Smith married a Liverpudlian, Arthur Bancroft,[2] in Edinburgh, Scotland. Records of her married life are scarce but it seems she was widowed twice. She died on 20 June 1923, in Oakland, California aged 82 bearing the surname de Cheney,[8] or de Chenez.[1]
References[edit]
^ Jump up to: a b "Charitie Lees De Chenez". The Canterbury Dictionary of Hymnology. Retrieved 27 January 2018.
^ Jump up to: a b c Robinson 1893, p. 208.
^ Jump up to: a b c O'Donoghue 1892, p. 16.
^ Jump up to: a b c Hatfield 1884, p. 35.
Jump up ^ Rogers 1868, p. 511.
Jump up ^ Robinson 1893, p. 474.
Jump up ^ Havergal 1881, p. 66.
Jump up ^ Barba 2012, p. 57.
Attribution[edit]
This article incorporates text from a publication now in the public domain: Hatfield, Edwin Francis (1884). The Poets of the Church: A Series of Biographical Sketches of Hymn-writers with Notes on Their Hymns (Public domain ed.). A. D. F. Randolph.
This article incorporates text from a publication now in the public domain: Havergal, Frances Ridley (1881). Specimen-glasses for the King's Minstrels (Public domain ed.). Anson D.F. Randolph.
This article incorporates text from a publication now in the public domain: O'Donoghue, David James (1892). The Poets of Ireland: A Biographical Dictionary with Bibliographical Particulars : in Three Parts (Public domain ed.). The author.
This article incorporates text from a publication now in the public domain: Robinson, Charles Seymour (1893). Annotations Upon Popular Hymns (Public domain ed.). Hunt & Easton.
This article incorporates text from a publication now in the public domain: Rogers, Charles (1868). Lyra Britannica: A Collection of British Hymns, Printed from the Genuine Texts, with Biographical Sketches of the Hymn Wirters (Public domain ed.). Longmans, Green.
Bibliography[edit]
Barba, Effie Darlene (1 June 2012). Ultimate Inspiration-God's Plan of Love. AuthorHouse. ISBN 978-1-4772-0592-1.
Further reading[edit]
Strahan, Jack (2002) More Hymns and Their Writers Glasgow, GTP.
External links[edit]
Works by or about Charitie Lees Smith at Internet Archive
Works by Charitie Lees Smith at LibriVox (public domain audiobooks)
Anglicanism portal
Authority control
WorldCat Identities
VIAF: 513149294079680520229
Retrieved from "https://en.wikipedia.org/w/index.php?title=Charitie_Lees_Smith&oldid=843353091"
Categories:
1841 births
1923 deaths
19th-century Irish writers
19th-century Irish women writers
People from County Dublin
Irish Anglican hymnwriters
Irish emigrants to the United States (before 1923)
American Episcopalians
Irish Anglicans
Christian hymnwriters
Pseudonymous writers
Pseudonymous women writers
Irish religious writers
Women religious writers
Hidden categories:
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