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UK Travel and Tours / A collecting agency assigned by mr barry atirson

1 Philippines Review updated:

i saw the job vacancy in the net this mr. barry atirson looking for a nanny in london and after applying thru email he assigned me to the london travel agency address was 5-11 lavington st london se1 0nz and want me to pay gbp550 that's for the application, visa etc. i searched the google and look for the company but unfortunately there was no travel agency matched. i think it's a scam like the paldin medico.

Ca
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Comments

  • Li
      19th of Jan, 2009
    +1 Votes

    i saw that job posting too! when i checked google, there's no such company as Uk Travels and Tours. I did a reverse phone lookup of the mobile number Mr Barry Atirson provided, and guess what I found? there were other ads with the exact same words, only that the names of the employer were altered.
    This travel agency wanted me to wire them 550Gbp in about 3days after i received all the visa and working permit application form.. I might wanna call The British Embassy to check on them.

  • Ja
      1st of Feb, 2009
    0 Votes

    hi i saw again adds rearding that and they want me to pay also to uk travel and tours, and i can find also that agency, what is the phone number that Mr. Barry Atirson Give it to you? can you pos it here so that this man stop geting money from others, thanks

  • Do
      2nd of Feb, 2009
    0 Votes

    Hi guy'.
    I too searched for the job and i found out that the same job "Nanny/ house keeper " was advertised and i was required to pay the workpermit through Uk Travels and Tours and the street adress is below, so i'm worndering weather this could be a trick for these guys to cheat us!!!
    the "-11 Lavington Street.
    London. SE1 0NZ"

  • Ja
      2nd of Feb, 2009
    0 Votes

    hi guys,

    Wher do you saw the post regarding that, yould you give me the name of the person that you gona send the money? manny thanks

  • Jm
      27th of Feb, 2009
    0 Votes

    I have applied to an employer named Shirley Smith as a House Chef. I had been accepted and she sent me a contract via e-mail through his Bar. Thomas Jefferson or Thomas Chambers. All went well, except for the agency, UK Travels and Tours Agency, 5-11 Lavington Street, London. The worst thing was he didn't want me to pay it personally but through western union. He insisted that i wire the money with this Federick Macpherson 30 Leicester Square. City, London, the he said was the agent of the said agency. It is clear, a big scam.

  • Jh
      6th of Mar, 2009
    +1 Votes

    jmm

    We have the same employer. i had been accepted as a nanny.And his lawyer Barr.Thomas Jefferson sent me the contract.And he advise me to send a copy of contract to the said agency.Please advice me if im going to pursue this job.Did you advise mr shirley about the problem with the agency? Please help me to decide thanks

  • Fi
      12th of Mar, 2009
    0 Votes

    fil

    same thing here, i was accepted as driver of mr smith shirley with same lawyer with the same agency. i don't know what to do so please help me this matter. are they exist?

  • Ve
      12th of Mar, 2009
    0 Votes

    this agency thing is a scam, the agency does not exist and the intrenet if full of this agency posting adverts on websites all over the world, i got an email from this agency from a guy called barrister moore even though I told them i live in the uk and i do not require a visa they still wanted me to pay for visa fee which i didnt need

    THIS IS A SCAM, DO NOT PAY THEES PEOPLE A PENNY, THEY GIVE THEMSELVES VERY ENGLISH NAMES AND WHEN YOU TALK ON THE PHONE TO THEM THEY HAVE FOREIGN INDIAN ACCENTS, THJIS IS A SCAM, THE SALARY THEY OFFER IS TOO HIGH FOR LONDON, NO REAL EMPLOYERS WOUL DOFFFER THAT MUCH TO PEOPLE THEY HAVE NOT EVEN INTERVIEWED THIS IS CRAZY

  • Ve
      12th of Mar, 2009
    0 Votes

    the person who tells that you have to deal with this travel agency so you pay the travel agency the money for the visa calls himself

    Thank you

    Mr. / Mrs. Michael Lawn

    +44 702 406 4870

    this is a fake name but a guy with a really bad english answers the phone

    i would suggest everyone calls this phobne number day and night swearing and screaming at him, during the night as well, so we taech him a lesson about scamming other people


    LETS STRESS HIM OUT GUYS, HE IS THE ONE AFTER YOUR MONEY THROUGH FRAUD

  • Ve
      12th of Mar, 2009
    0 Votes

    THIS IS A BIG SCAM AND THE AD POSTED BY THIS GUY I SAW ON HALLOLONDON.CO.UK IN THE NANNY SECTION


    LETS STRESS HIM OUT GUYS

  • Ve
      12th of Mar, 2009
    0 Votes

    Good Day,



    I have received your Message Regarding the Nanny Job you requested. so we have considered hiring you for your services(...NANNY...).



    However, as regards to your flight ticket that we will be handling, and also other relevant documents you will need to process before you can traveling into the UK will be sent to you through our lawyer, but you have to know you will have to acquire a working permit which will enable you work in England.



    So if you agree with these terms and conditions of services, please let us know so that we can have our lawyer issue you contract/invitation letter and also all the necessary details on how to obtain your traveling papers. You can call us anytime for your interview. You can get our mobile number below.



    Thank you

    Mr. / Mrs. Michael Lawn

    +44 702 406 4870


    Hello,
    How are you doing?After talking with my client, he has authorized me to send you this email.I am attaching herewith a Contract/Invitation Letter from Engr JONES MARTINS, for you to go through. If you accept, you would have to sign and date at the bottom and send a scanned copy to me as e mail attachment.


    Information For Travel.

    Your employer went to the UK Immigrations Office here in London to inform them about his decision to employ you and to also seek their approval/permit as they are the legal authorities vested with the power to permit/approve foreign workers.
    You have to contact them immediately you sign the contract letter. Send a copy to them and also request them to furnish you with details of how you can get your work permit and travel documents.Also you should know that your employer, would share travel costs with you, he will pay them for your Flight Ticket and some other relevant documents, and the little you would spend is the cost of obtaining your Work Permit
    okay. Here are their contact details:

    Uktravels & Tours Agency

    5-11 Lavington Street.
    London. SE1 0NZ
    Email: uk_travels_tour@mail2world.com

    Send them an e mail with a copy of the signed contract letter and
    they would get in touch with you so that you can travel down
    soonest to resume duties.

  • Sh
      14th of Mar, 2009
    0 Votes

    This is a copy of emails i got today.same style and same Address oh how this person collects money from all of us...



    From:
    "Barrister Solicitor"

    Hello,
    How are you doing? After talking with my client, she has authorized me to send you this email.I am attaching herewith a Contract/Invitation Letter from Mr & Mrs Henshaw, for you to go through. If you accept, you would have to sign and date at the bottom and send a scanned copy to me as e mail attachment.

    Information For Travel.
    Your employer went to the UK Immigrations Office here in London to inform them about his decision to employ you and to also seek their approval/permit as they are the legal authorities vested with the power to permit/approve foreign workers.
    You have to contact them immediately you sign the contract letter. Send a copy to them and also request them to furnish you with details of how you can get your work permit and travel documents.Also you should know that your employer, would share travel costs with you, he will pay them for your Flight Ticket and some other releva nt documents, and the little you would spend is the cost of obtaining your Work Permit okay.

    Here are their contact details:
    Uktravels & Tours Agency
    5-11 Lavington Street.
    London. SE1 0NZ
    Email: travelways@mail2world.com


    Send them an e mail with a copy of the signed contract letter and they would get in touch with you so that you can travel down soonest to resume duties.
    Best Regards
    Barrister Allan Heffingham

    -----------------------------------------------------------------------------------------------------------------------------------------------------------------
    When will this gonna end?



    From:
    "Travel Ways"

    Attn:
    I received correspondence of contract agreement documents .Find herewith attached information's required for the procurement of your traveling documents.Applicants to whom we have confirmed contract agreement letter of invitation from individual employee his/her permitted to go through the required Visa/Work Permit Documents carefully and you are required to complete the requirements to enable us finish the processing and send it to you, and also to the British Embassy in your country for your Schedule date of interview. Please note that the cost of Visa and Prepaid Flight Tickets has been undertaken by your employer.

    This will enable us commence and finalize all your necessary work permit/Visa registration of documents as we need to reach out to our contact for immediate procurement of your visa and other supporting documents in record time.

    All documents should be completed and scan to us within three (3) working days for immediate confirmation. You will be required to scan and send immediately. Thereafter, we shall inform you on how you can make payments for work permits registration as required.

    Best Regard
    BRUNO ARANTIS...


    I just got this Today!!?..so be careful guys...

  • We
      22nd of Mar, 2009
    0 Votes

    its good that i have browse this page.because i am in the same situation now.mr smith send the same letter that was sent to u guys...and he even added me on his ym list. as i read the email that he sent to me, i have a doubt about it because its unusual that i will get hired with just a click of a mouse and doesnt even know me well since i havent send my resume to mr smith yet..so i added him and got curious about this..we chatted on line to get the details..he asked me to send 299 pounds within 2 days for my work permit i just said yes for me to get more info about the scam.i tried to ask if i can pay it through salary deductions, but he refused since i havent work there yet...ok i said..but it has to go through the poea processing since this a new law..i told him..he refused again...now i came into the conclusion that this definitely a scam...dont believe on him...or else just waste ur money...remember...we are looking for a job because we need money...not that we are giving away money to this kind of people with no soul...may god have mercy on them.

  • Ne
      23rd of Mar, 2009
    0 Votes

    HELLO I am Netsanet from ethiopia, I recived job opprtunity from Mrs. Barrister Jerry southerland, how could you help me to start my process

  • El
      28th of Mar, 2009
    0 Votes

    HI ALL,

    YES, I WAS FANTASIZING ABOUT GOING TO LONDON...THINKING OF DIFFERENT TYPES OF RECIPES...ONLY TO REALISE THAT IS ALL A SCAM...WELL, WHO EVER IS INVOLVED LIFE WILL NOT BE THE SAME...THERE IS SUCH A THING AS KARMA...AND BOY OH BOY THEY ARE GOING TO GET IT. SO TO ALL THOSE, LIKE ME, ALSO WANTING THIS OPPERTUNITY SO MUCH, KEEP IT UP. DON'T STOP TRYING AND LET THIS BE A WARNING SIGN THAT THERE ARE NUMEROUS WEIR PEOPLE WITH BAD HABITS. WE ALL LEARNT FROM THIS. O AND SO BY THE WAY, I'M AN EX COP. THE WRONG PERSON TO CROSS. LET'S ALL UNITE TO IN THE ENERGY WORLD AND SEND THESE PEOPLE BACK WHAT THEY DONE TO US.

    KEEP UP THE GOOD SPIRITS

    BERNICE SALMON
    SOUTH AFRICA

  • Je
      14th of Apr, 2009
    0 Votes

    These are the emails I got. Thank God i have browsed this page.
    To hell with these people!

    SHERATON TOWER HOTEL
    169 coleshire
    London SW1X 7RN
    United Kingdom
    BAYS WATER, LONDON.
    sheraton-towerhotel@mail.com
    sheraton-park-tower-hotel@hotmail.com
    www.sheraton66.webs.com

    Dear Applicant,

    We have received your Message Regarding the Job you requested.We have considered hiring you for your services.

    However, We are going to be responsible for your flight ticket and other relevant documents you will need to proceed into England will be sent to you through our Employment Manager.

    You have to pay for your work permit papers so that you can work here in the UK without any embarrassment from the British Authorities.

    If you are okay with these terms and conditions of services, please let us know so that we can have our Employment Manager issue you contract/invitation letter and also all the necessary details on how to obtain your traveling papers.

    You can call the Employment Manager anytime you wish to take the interview. You can call his mobile number below OR send an email to sheraton-towerhotel@mail.com for your interview.

    Note: you can also hook up with our agent for your interview at sheraton-towerhotel@mail.com

    Appointment Manager : GYLES FOSTER
    +447045753952, +447024074896

    Best Regards,
    Management.

    Dear Applicant

    We are sending you this message to acknowledge you as our latest worker., You have shown us now that you have agreed to the terms and conditions of this hotel management. We presume that you will do your job absolutely perfect to our taste

    In order for you to commence with this application. You have to contact our lawyer inorder for him to furnish you with the contract/invitation letter. You are to fill this brief form below and forward to him immediately .

    Name:
    Mobile Phone Number:
    Country:
    Address:
    Job Granted:
    Intended Salary to be earned:

    Note: Our lawyers details is stated below

    Barrister John Kennedy
    Email: barristerken49@yahoo.co.uk


    Attn: Client,

    How are you doing? After talking with my
    client (SHERATON TOWER HOTEL), he has authorized me to send you this email. I am attaching
    herewith a Contract/Invitation Letter from Engr. Harry Jones, for you to
    go through. If you accept, you would have to sign and date at the
    bottom and send a scanned copy to me as e mail attachment.

    Information for Travel.

    Your employer went to the UK Immigrations Office here in London to
    inform them about his decision to employ you and to also seek their
    approval/permit as they are the legal authorities vested with the
    power to permit/approve foreign workers.

    You have to contact them
    immediately you sign the contract letter. Send a copy to them and
    also request them to furnish you with details of how you can get
    your work permit and travel documents. Also you should know that
    your employer, would share travel costs with you, he will pay them
    for your Flight Ticket and some other relevant documents, and the
    little you would spend is the cost of obtaining your Work Permit
    okay. Here are their contact details:

    Uktravels & Tours Agency

    5-11 Lavington Street.
    London. SE1 0NZ

    Email: traveagency@yahoo.co.uk

    Send them an e mail with a copy of the signed contract letter and
    they would get in touch with you so that you can travel down
    soonest to resume duties.

    Best Regards
    Barr. John kennedy

  • Ga
      8th of May, 2009
    0 Votes

    ulation of Enzyme Activity

    There are many ways to regulate enzyme activity at different levels:
    1) regulation of rate of synthesis or degradation
    • Is fairly slow (several hours), so is really too slow to be effective in eucaryotic cells.
    • Need something that can occur in seconds or less.
    • Usually done through regulatory enzymes and occur in metabolic pathways early or at first committed step:

  • Ga
      8th of May, 2009
    0 Votes

    Chapter 5 - Properties of Enzymes

    Characteristics of enzymes
    1) biological catalysts
    2) not consumed during a chemical reaction
    3) speed up reactions from 1000 - 1017, with a mean increase in rate of 00, 000
    4) exhibit stereospecificity --> act on a single stereoisomer of a substrate
    5) exhibit reaction specificity --> no waste or side reactions


    Nomenclature

    Typically add “-ase” to name of substrate
    e.g. lactase breaks down lactose (dissacharide of glucose and galactose)

    IUBMB classifies enzymes based upon the class of organic chemical reaction catalyzed:
    1) oxidoreductase - catalyze redox reactions
    dehydrogenases, oxidases, peroxidases, reductases
    2) transferases - catalyze group transfer reactions; often require coenzymes
    3) hydrolases - catalyze hydrolysis reactions
    4) lyases - lysis of substrate; produce contains double bond
    5) isomerases - catalyze structural changes; isomerization
    6) ligases - ligation or joining of two substrates with input of energy, usually from ATP hydrolysis; often called synthetases or synthases

    Enzyme kinetics:

    A mathematical and graphical study of the rates of enzyme-catalyzed reactions.
    k
    S -----------> P
    k
    A + B ---> C

    The velocity of this reaction can be summarized by the following equation:

    v = k[S] or v = k[A][B]

    This reaction is considered a first order reaction, determined by the sum of the exponents in the rate equation --> number of molecules reacting.

    There are also bimolecular reactions, which involve two substrates; good example of group transfer reactions.

    S1 + S2 ---> P1 + P2

    v = k[S1][S2] first order for each reactant; but second order overall

    For enzyme-catalyzed reactions:

    E + S -----> ES -----> E + P

    The rate or velocity is dependent upon both [enzyme] and [substrate].

    In reality, enzyme-catalysed reactions are not that simple:
    k1 kcat
    E + S ES E + P
    k-1

    k1 and k-1 govern the rates of association and dissociation of ES
    kcat is the turnover number or catalytic constant

    VES = k1[E][S]
    VE+S = k-1[ES]
    VE+P = kcat[ES]

    Usually an enzyme’s velocity is measured under initial conditions of [S] and [P].

    These same reactions can be described graphically:


    velocity


    [S]

    • At low [S], vo increases as [S] increases.
    • At high [S], enzymes become saturated with substrates, and the reaction is independent of [S] --> display saturation kinetics.

    Vmax = kcat[ES]

    or because the [S] is irrelevant at high [S]

    Vmax = kcat [E]

    The graph is a graph of a hyperbola, and the equation for a hyperbola is

    y = ax
    b + x where a is the asymptote
    b is value at a/2
    Substituting our equation parameters,

    Vo = Vmax[S]
    Km + [S] Michaelis-Menten equation

    Different enzymes reach Vmax at different [S] because enzymes differ in their affinity for the substrate or Km.
    1) The greater the tendency for an enzyme and substrate to form an ES, the higher the enzyme’s affinity for the substrate ---> lower Km.
    2) At a given [S], the more enzyme will be in ES for an enzyme with a higher affinity
    i.e. the greater the affinity, the lower the [S] needed to saturate the enzyme or to reach Vmax.

    Enzyme-substrate affinity and reaction kinetics are closely associated
    [S] at which vo=1/2Vmax = Km

    Km is a measure of enzyme affinity


    Km = k-1
    k1 reflection of association and dissociation of ES

    • a small Km (high affinity) favors E + S ----> ES
    • a large Km (low affinity) favors ES -----> E + S
    • meaning that the lower the Km, the less substrate is needed to saturate the enzyme.

    We would like numbers of Vmax and Km for a means of comparison among enzymes.

    It is difficult to estimate Vmax and Km from a typical graph of [substrate] vs. velocity.

    These two parameters are used to describe the efficiency of enzymes; must be an easier method for measuring these parameters.

    Done by transformation of the date by taking the reciprocal of both sides of the equation ---> double reciprocal plot or Lineweaver-Burke plot.

    Vo = Vmax[S]
    Km + [S]

    1 Km 1 1
    Vo = Vmax [S] + Vmax y=mx+b


    Alterations in enzyme activity:

    Enzyme inhibition
    • Molecule that binds to enzyme and interferes with its activity to prevent either:
    1) formation of ES complex E + I ---> EI
    2) breakdown of ES --> E + P ES + I ---> ESI
    • Used to regulate metabolism.
    • Many drugs act by enzyme inhibition.
    • These molecules can be
    1) irreversible - bind to enzymes by covalent means and modify enzyme
    2) reversible - noncovalent binding to enzyme

    There are three types of reversible inhibition:
    1) competitive
    • Competes with substrate for active site of enzyme.
    • Both substrate and competitive inhibitor bind to active site.
    • These inhibitors are often substrate analogs (similar in structure substrate), but still no product is formed.
    • Can be overcome by addition of more substrate (overwhelm inhibitor; a numbers game).
    e.g. malonate inhibition of succinate dehydrogenase

    succinate ----------------------> fumarate

    FAD FADH2



    succinate malonate

    e.g. AZT inhibition of HIV reverse transcriptase
    actual substrate is dTTP (deoxythymidine triphosphate)
    • Can be represented by the following equation:

    E + S ES E + P
    +
    I


    EI

    • Graphical representation of competitive inhibitors:

    • affects Km (increases Km --> decreases affinity; need more substrate to reach half-saturation of enzyme)
    • Vmax unaffected

    2) uncompetitive inhibitor
    • Typically seen in multisubstrate reactions (here, there is a decrease in product formation because the second substrate cannot bind).
    • Inhibitor binds to ES, but not enzyme.

    E + S ES E + P
    +
    I


    ESI
    Graphical representation of uncompetitive inhibitors:



    Lineweaver-Burke plot:
    • both Km and Vmax are lowered, usually the same amount
    • ratio Km/Vmax unchanged --> no change in slope

    3) pure noncompetitive inhibitor
    • Can bind to enzyme and ES complex equally.
    • Does not bind to same site as substrate and is not a substrate analog.
    • Cannot be overcome by increases in [substrate].
    e.g. lead, mercury, silver, heavy metals

    Lineweaver-Burke plot:
    • No effect on Km, because those enzyme molecules unaffected have normal affinity.
    • Vmax is lowered.


    ulation of Enzyme Activity

    There are many ways to regulate enzyme activity at different levels:
    1) regulation of rate of synthesis or degradation
    • Is fairly slow (several hours), so is really too slow to be effective in eucaryotic cells.
    • Need something that can occur in seconds or less.
    • Usually done through regulatory enzymes and occur in metabolic pathways early or at first committed step:

    Reg



    E1
    A + B ---> C ---> D ---> E --->F ---> P feedback inhibition

    G ---> H

    • Result is to conserve material and energy by preventing accumulation of intermediates.

    2) allosteric regulation
    • Done through allosteric sites or regulatory sites on enzymes - site other than active site where inhibitor or activator can bind.
    • Properties of allosteric enzymes:
    1) sensitive to metabolic inhibitors and activators
    2) binding is noncovalent; not chemically altered by enzyme
    3) regulatory enzymes possess quaternary structure - individual polypeptide chains may or may not be identical
    4) enzyme has at least one substrate that gives sigmoidal curve due to positive cooperativity because of multiple substrate binding sites.
    • Theories of allosteric regulation:
    1) concerted theory or symmetry-driven theory
    Assumes 1 binding site/subunit for each ligand.
    Enzyme can assume either R or T conformation.
    Assumes that all subunits are in R or T state, and all switch at same time when the first substrate is bound.

    2) sequential theory
    Ligand introduces a change in the tertiary structure of a subunit.
    Only that subunit is converted to R conformation.

    3) covalent modification
    • Usually requires one enzyme to activate enzyme and another to inactivate.
    • Most common modification is phosphorylation of serine residues on interconvertible enzyme (the one that does the activating).
    e.g. pyruvate dehydrogenase


    Chapter 16 - Lipid Metabolism

    Fatty acids have four major physiologic roles in the cell:
    • Building blocks of phospholipids and glycolipids
    • Added onto proteins to create lipoproteins, which targets them to membrane locations
    • Fuel molecules - source of ATP
    • Fatty acid derivatives serve as hormones and intracellular messengers


    Absorption and Mobilization of Fatty Acids
    • Most lipids are triacylglycerols, some are phospholipids and cholesterol.
    • Digestion occurs primarily in the small intestine.
    • Fat particles are coated with bile salts (amphipathic) from gall bladder.
    • Degraded by pancreatic lipase (hydrolyzes C-1 and C-3 ---> 2 fatty acids and 2-monoacylglycerol).
    • Can then be absorbed by intestinal epithelial cells; bile salts are recirculated after being absorbed by the intestinal epithelial cells.
    • In the cells, fatty acids are converted by fatty acyl CoA molecules.
    • Phospholipids are hydrolyzed by pancreatic phospholipases, primarily phospholipase A2.
    • Cholesterol esters are hydrolyzed by esterases to form free cholesterol, which is solubilized by bile salts and absorbed by the cells.
    • Lipids are transported throughout the body as lipoproteins.
    • Lipoproteins consist of a lipid (tryacylglycerol, cholesterol, cholesterol ester) core with amphipathic molecules forming layer on outside.

    Lipoproteins

    • Both transported in form of lipoprotein particles, which solubilize hydrophobic lipids and contain cell-targeting signals.
    • Lipoproteins classified according to their densities:
    o chylomicrons - contain dietary triacylglycerols
    o chylomicron remnants - contain dietary cholesterol esters
    o very low density lipoproteins (VLDLs) - transport endogenous triacylglycerols, which are hydrolyzed by lipoprotein lipase at capillary surface
    o intermediate-density lipoproteins (IDL) - contain endogenous cholesterol esters, which are taken up by liver cells via receptor-mediated endocytosis and converted to LDLs
    o low-density lipoproteins (LDL) - contain endogenous cholesterol esters, which are taken up by liver cells via receptor-mediated endocytosis; major carrier of cholesterol in blood; regulates de novo cholesterol synthesis at level of target cell
    o high-density lipoproteins - contain endogenous cholesterol esters released from dying cells and membranes undergoing turnover
    Storage of Fatty Acids
    • Triacylglycerols are transported as chylomicrons and VLDLs to adipose tissue; there, they are hydrolyzed to fatty acids, which enter adipocytes and are esterified for storage.
    • Mobilization is controlled by hormones, particularly epinephrine, which binds to -adrenergic receptors on adipocyte membrane --> protein kinase A activated --> phosphorylates hormone-sensitive lipase --> converts triacylglycerols to free fatty acids and monoacylglycerols.
    • Insulin inhibits lipid mobilization (example of reciprocal regulation).
    • Monoacylglycerols formed are phosphorylated and oxidized to DHAP (intermediate of glycolysis and gluconeogenesis).

    ATP ADP NAD+ NADH + H+

    glycerol glycerol 3-phosphate dihydroxyacetone phosphate
    glycerol kinase glycerol phosphate
    dehydrogenase

    Can be converted to glucose (gluconeogenesis) or pyruvate (glycolysis) in the liver.

    Fatty Acid Oxidation (-oxidation)
    • Fatty acids are degraded by oxidation of the carbon by-oxidation.
    • Pathway that removes 2-C units at a time --> acetyl CoA --> citric acid cycle --> ATP
    • There are three stages in -oxidation:
    o Activation of fatty acids in cytosol catalyzed by acyl CoA synthetase; two high energy bonds are broken to produce AMP
    o 2) Transport of fatty acyl CoA into mitochondria via carnitine shuttle
    o 3) -oxidation - cyclic pathway in which many of the same enzymes are used repeatedly (see pathway sheet)


    -oxidation of odd chain and unsaturated fatty acids

    • Odd chain fatty acids undergo -oxidation until propionyl CoA is formed.
    • Propionyl CoA is then converted to succinyl CoA, which then enters the Krebs cycle.
    • See pathway sheet for details

    • Unsaturated fatty acids need two additional enzymes besides those of-oxidation.
    o enoyl-CoA isomerase
    o 2, 4-dienoyl-CoA reductase
    • How the pathway looks depends upon the location of the double bond, but there are two possibilities.
    • See pathway sheets for details.


    ATP generation from Fatty Acid Oxidation:

    • Can be estimated from the amount of acetyl CoA, QH2, and NADH produced.
    • See pathway sheet.

    Regulation of Fatty Acid Oxidation

    • Already talked about fatty acid mobilization via epinephrine.
    • Net result is high concentrations of acetyl CoA and NADH via -oxidation.
    • Both molecules allosterically inhibit pyruvate dehydrogenase complex.
    • Most of acetyl CoA produced goes to Krebs cycle; during periods of fasting, excess acetyl CoA is produced, too much for Krebs cycle.
    • Also in diabetes, oxaloacetate is used to form glucose by gluconeogenesis --> concentration of oxaloacetate is lowered.
    • Result is the diversion of acetyl CoA to form acetoacetate and 3-hydroxybutyrate; these two molecules plus acetone are known as ketone bodies.
    • Acetoacetate is formed via the following reactions:

    acetyl
    CoA CoA acetyl CoA
    2 acetyl CoA 3-hydroxy- acetoacetate HMG-CoA lyase
    3-methylglutaryl CoA

    NADH + H+ -hydroxy H+ NAD+ butyrate CO2
    Dehydrogenase

    3-hydroxybutyrate acetone

    • The major site of ketone body synthesis is the liver, within the mitochondrial matrix ---> transported to the bloodstream.
    • Acetoacetate and 3-hydroxybutyrate are used in respiration and are important sources of energy.
    • Cardiac muscle and the renal cortex perferentially use acetoacetate over glucose.
    • Glucose is used by brain and RBCs; in brain, ketone bodies substitute for glucose as fuel because the brain cannot undergo gluconeogenesis.
    • Acetoacetate can be converted to acetyl CoA and oxidized in citric acid cycle only in nonhepatic tissues.

    Diabetes (insulin-dependent diabetes mellitus; IDDM)
    Decreased insulin secretion by beta cells of pancreas; could be caused by viruses (?)
    Juvenile onset
    Patients are thin, hyperglycemic, dehydrated, polyuric (pee a lot), hungry, thirsty
    In these patients, glycogen mobilization, gluconeogenesis, fatty acid oxidation occurs --- > massive ketone body production; also, some of the glucose is in urine (tends to pull water out of body) ----> diabetic ketoacidosis


    FATTY ACID SYNTHESIS

    Important features of this pathway:
    1) Synthesis takes place in cytosol; -oxidation takes place in mitochondrial matrix.
    2) Intermediates are bound to sulfhydral groups of acyl carrier protein (ACP); intermediates of-oxidation are bonded to CoA
    3) Growing fatty acid chain is elongated by sequential addition of two-carbon units derived from acetyl CoA
    4) Reducing power comes from NADPH; oxidants in -oxidation are NAD+ and FAD
    5) Elongation of fatty acid stops when palmitate (C16) is formed; further elongation and insertion of double bonds carried out later by other enzymes


    Fatty acid synthesis takes place in three stages:
    1) Mitochondrial acetyl CoA is transported into cytosol via citrate transport system
    Acetyl CoA is condensed with oxaloacetate to form citrate ---> antiported out with inward movement of anion
    Citrate cleaved by cytosolic citrate lyase --> oxaloacetate + acetyl CoA
    2) Formation of malonyl CoA
    Acetyl CoA carboxylase is key regulatory enzyme
    Influenced by glucagon --> inactivates enzyme in liver
    Epinephrine inactivates enzyme in adipocytes
    Citrate allosterically activates enzyme
    Fatty acyl CoA allosterically inhibits enzyme
    3) Assembly of fatty acid chain via fatty acid synthase
    Consists of five separate stages:
    1) Loading - acetyl CoA and malonyl CoA are attached to acyl carrier protein
    2) Condensation - both are condensed by fatty acid synthase to from acetoacetyl-ACP
    3) Reduction - NADPH is oxidized to form hydroxybutyryl ACP
    4) Dehydration - formation of double bond
    5) Reduction - NADPH is source of e- and H+ to form butyryl-ACP

    Last four steps are repeated, each time with malonyl-ACP to elongate chain, until palmitate is produced.


    Overall reaction:

    acetyl CoA + 7 malonyl CoA + 14 NADPH + 20 H+ ---> palmitate + 7CO2 + 14 NADP+ + 8 HS-CoA + 6 H2O

    Regulation of Fatty Acid Synthesis

    • Metabolism of fatty acids is under hormonal regulation by glucagons, epinephrine, and insulin.
    • Fatty acid synthesis is maximal when carbohydrate and energy are plentiful.
    • Important points of control are release of fatty acids from adipocytes and regulation of carnitine acyltransferase I in the liver.
    • High insulin levels also stimulate formation of malonyl CoA, which allosterically inhibits carnitine acyltransferase I  fatty acids remain in cytosol and are not transported to mitochondria for oxidation.
    • Key regulatory enzyme is acetyl-CoA carboxylase (catalyzes first committed step in fatty acid synthesis).
    • Insulin stimulates fatty acid synthesis and inhibits hydrolysis of stored triacylglycerols.
    • Glucagon and epinephrine inhibit fatty acid synthesis (enzyme is phosphorylated by protein kinase A; removal of phosphate group catalyzed by protein phosphatase 2A).
    • Citrate is an allosteric activator, but its biological relevance has not been established.
    • Fatty acyl CoA acts as an inhibitor.
    • Palmitoyl CoA and AMP are allosteric inhibitors.


    Synthesis of Eicosanoids

    • Precursors for eicosanoids are 20-carbon polyunsaturated fatty acids such as arachidonate.
    • Part of inner leaflet of cell membrane.
    • There are two classes of eicosanoids:
    1) prostaglandins and thromboxanes
    Synthesized by enzyme cyclooxygenase
    Localized molecules such as thromboxane A2, prostaglandins, prostacyclin ae produced.
    Thromboxane A2 leads to platelet aggregation and blood clots  reduced blood flow in tissues.
    Aspirin binds irreversibly to COX enzymes and prevents prostaglandin synthesis.
    2) leukotrienes
    Produced by lipoxygenases.
    Products were once called “slow-acting substances of anaphylaxis”, responsible for fatal effects of some immunizations.
    Synthesis of Triacylglycerols and Glycerophospholipids

    Most fatty acids are esterified as triacylglycerols or glycerophospholipids.
    Intermediate molecule in synthesis of these two molecules is phosphatidic acid or phosphatidate.

    There are two pathways:
    1) de novo – “from scratch”
    2) salvage pathway - uses “old” pieces and parts to make new molecules

    Synthesis of phosphatidate:
    • Common intermediate in synthesis of phosphoglycerides and triacylglycerols
    • Formed from glycerol 3-phosphate and 2 acetyl CoA molecules
    • Enzyme is glycerol phosphate acyltransferase

    Synthesis of triacylglycerols and neutral phospholipids:
    • Uses phosphatidate, which is dephosphorylated to produce 1, 2-diacylglycerol
    If acetylated ---> triacylglyerol
    If reacted with nucleotide derivative --> phosphatidylcholine or phosphatidylethanolamine

    Synthesis of acidic phospholipids:
    • Uses phosphatidate and reacts it with CTP ---> CDP-diacylglycerol
    • Addition of serine --> phosphatidylserine
    • Addition of inositol ---> phosphatidylinositol
    • In mammals, phosphatidylserine and phosphatidylethanolamine can be interconverted - base-exchange occurs in ER.
    • Decarboxylation occurs in mitochondria and procaryotes


    Synthesis of Sphingolipids

    • All have C18 unsaturated alcohol (sphingosine) as structural backbone, rather than glycerol
    • Palmitoyl CoA and serine condense ---> dehydrosphinganine ---> sphingosine
    • Acetylation of amino group of sphingosine ---> ceramide
    • Substitution of terminal hydroxyl group gives:
    • sphingomyelin -- addition of phosphatidylcholine
    • cerebroside -- substitute UDP-glucose or UDP-galactose
    • gangliosides -- substitute oligosaccharide

    Tay-Sachs disease = inherited disorder of ganglioside breakdown.
    • Deficient or missing enzyme is -N-acetylhexosaminidase, which removes the terminal N-acetylgalactosamine residue from its ganglioside.
    • One in 30 Jewish Americans of eastern European descent are carriers of a defective allele.
    • Can be diagnosed during fetal development by assaying amniotic fluid for enzyme activity.
    • Causes weakness, ###ed psychomotor development, blindness by age two, and death around age three.

    Synthesis of Cholesterol

    • Precursor of steroid hormones and bile salts.
    • Most cholesterol is synthesized in liver cells, although most animal cells can synthesize it.
    • Starts with 3 molecules of acetyl CoA to form 3-hydroxy-3-methyl-glutaryl CoA, which is reduced to mevalonate (C6) by HMG-CoA reductase (first committed step of cholesterol synthesis)
    • Amount of cholesterol formation by liver and intestine is highly responsive to cellular levels of cholesterol.
    • Enzyme HMG-CoA reductase is controlled in multiple ways:
    1) Rate of enzyme synthesis is controlled by sterol regulatory element (SRE); SRE inhibits mRNA production
    2) Translation of reductase mRNA is inhibited by nonsterol metabolites derived from mevalonate
    3) Degradation of the enzyme occurs at high enzyme levels
    4) Phosphorylation of enzyme
    If enzyme is phosphorylated via glucagon pathway --> decreased activity--> cholesterol synthesis ceases when ATP levels are low
    If enzyme is dephosphorylated via insulin pathway --> increased activity


    • Cells outside liver and intestine obtain cholesterol from blood instead of synthesizing it de novo.
    • Steps in the uptake of cholesterol by LDL pathway:
    1) apolipoprotein on surface of LDL particle binds to receptor on membrane of nonhepatic cells
    2) LDL-receptor complex internalized by endocytosis
    3) vesicles formed fuse with lysosomes, which breaks apart protein part of lipoprotein to amino acids and hydrolyzes cholesterol esters
    4) released unesterified cholesterol can be used for membrane biosynthesis or be reesterified for storage

    • Defects in LDL receptor lead to familial hypercholesterolemia (FH), in which cholesterol and LDL levels are markedly elevated.
    • Result is deposition of cholesterol in tissues because of high levels of LDL-cholesterol in blood
    • Heterozygotes suffer from atherosclerosis and increased risk of stroke
    • Homozygotes usually die in childhood from coronary artery disease
    • Disease is the result of an absence (homozygotes) or reduction (heterozygotes) in number of LDL receptors.
    • LDL entry into liver and other cells is impaired.
    • Drug therapy can help heterozygotes
    1) can inhibit intestinal absorption of bile salts (which promote absorption of dietary cholesterol)
    2) lovastatin - competitive inhibitor of HMG-CoA reductase ---> blocks cholesterol synthesis

  • Je
      4th of Jun, 2009
    0 Votes

    A scam!!muntik na ako!!
    By:jerome of Philippines
    Attn:
    I received correspondence of the contract agreement between you and The family of Engr Lucas Moore.
    Find the attached information's required for the procurement of your traveling documents, Applicants to whom we have confirmed contract agreement letter of invitation from individual employee his/her permitted to go through the required Work Permit Documents carefully and you are required to complete the requirements to enable us finish the processing and send it to you. Please note that the cost of other documents and Prepaid Flight Tickets has been undertaken by your employer.

    This will enable us commence and finalize all your necessary work permit, registration of documents as we need to reach out to our contact for immediate procurement of your other supporting documents in record time.
    All documents should be completed and scan to us within 24hours for immediate confirmation. You are required to scan and send along with the payment confirmation slip from western union for the work permit.

    Best Regard
    BRUNO ARANTIS...
    Uktravels & Tours Agency
    5-11 Lavington Street.
    London. SE1 0NZ

  • Pe
      4th of Jun, 2009
    +1 Votes

    that FU__n' guy just called earlier and told me that he sent me the contract in my email for hiring me as a project manager with 20000 GBP salary and I should send him and that travel agency a signed copy for them to apply for my work permit. Im glad that I background check that agency and I stumbled upon these blogs/ comments and I learned the truth behind this scam. but i will not tell them that I already know. I WILL LET THEM CALL ME OFTEN SO THEY WILL SPEND MONEY ON THE PHONECALLS!!! ITS PAYBACK TIME HAHAHAHAHAHA!!!

    ---PERIBOI

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