Download Free Medical Fate of Glucogenic and Ketogenic Amino Acid PowerPoint Presentation

Fate of Glucogenic and Ketogenic Amino Acid PowerPoint Presentation

DOWNLOAD MEDICAL POWERPOINT PRESENTATION

About This Presentation

Description : Amino acid are the currency of of nitrogen and protein economy of the host, hence they are used in many pathways beyond protein synthesis, including energy production and neurotransmitter synthesis.

Tags : biochemistry,glucogenic,Ketogenic Amino Acid

Published on : Dec 08, 2022 | Views : 2017 | Downloads : 3

Shareable Url :

Embed Code :

Comment

Transcript

Slide 1-

Fate of Glucogenic and Ketogenic amino acid Class- Bsc bioscience 6th semester Section – D
Slide 2-

Introduction Amino acid are the currency of of nitrogen and protein economy of the host, hence they are used in many pathways beyond protein synthesis, including energy production and neurotransmitter synthesis. All amino acid are comprised of an amino group and a carbon skeleton. During metabolism these two parts are separated as they have different ‘fates’ Of the liberated amino acid approximately 75% are utilized while remainder serve as precursors for important biological compound and those not utilized are degraded to amphibolic intermediates The pathway of amino acid catabolism is quite similar in most organism
Slide 3-

Site of amino acid metabolism Intestine- amino acid from protein digestion are absorbed. Intestine preferably uses glutamine and asparagine as energy supplier, product formed with remaining amino acid are sent to liver via portal vein Liver- all amino acid except branched chain catabolism start here. The amine group is seprated and incorporated in urea and carbon skeleton is either oxidized in CO2 and H2O or used for gluconeogenesis and ketogenesis Muscle- degradation of branched chain amino acid start in skeletal muscle. The amine group are transferred to pyruvate to form alanine. The muscle amino acid released in circulation are mainly alanine and glutamine that act as carriers of amine from other tissue Kidney- organ captures glutamine released from muscle and catabolized it to release ammonium with help of glutaminase and glutamte dehydrogenase
Slide 4-

Overview of metabolism of amino acid .
Slide 5-

ppt slide no 5 content not found
Slide 6-

Transamination It is first step of L-amino acid catabolism Most common amino acid (except lysine, threonine and imino acid) can be converted into corresponding keto acid by transamination In this the α-amino group is transferred to the α-carbon atom of α-ketoglutarate, leaving behind the corresponding α-keto acid analog of the amino acid, There is no net deamination in these reaction because the α-ketoglutarate becomes aminated as the α-amino acid is deaminated It is reversible and catalyzed by Transaminase or amino transferase. The effect of transamination reactions is to collect the amino groups from many different amino acids in the form of L-glutamate
Slide 7-

Pyridoxal phosphate and Aminotransferase All aminotransferase require the prosthetic group Pyridoxal phosphate(PLP) which is derived from Pyridoxine(vitamin B6) Pyridoxal phosphate is generally covalently bound to the enzyme’s active site through an aldimine (Schiff base) linkage to the ε-amino group of a Lys residue Pyridoxal phosphate participates in a variety of reactions at the α, β, and γ carbons (C-2 to C-4) of amino acid It undergoes reversible transformation between aldehyde form(pyridoxal phosphate) and animated form(pyridoxamine phosphate) Pyridoxal phosphate, the prosthetic group of aminotransferases (a) Pyridoxal phosphate (PLP) and its aminated form, pyridoxamine phosphate
Slide 8-

Reaction at α- carbon
Slide 9-

Oxidative deamination of Glutamate The nitrogen atom that is transferred to α-ketoglutarate in transamination reaction forming glutamate is concerted into free ammonium ion by oxidative deamination This reaction occur in hepatocytes cell mitochondria Reaction is catalyzed by glutamate dehydrogenase that is located in mitochondria. This enzyme is unusual in being able to utilize either NAD+ or NADP+ L-glutamate is the only amino acid that undergoes oxidative deamination at appreciable rate The ammonia released is incorporated into urea by urea cycle
Slide 10-

Role of glutamate dehydrogenase Their activity is allosterically regulated Enzyme consist of six identical sub-unit Guanosine triphosphate(GTP) and Adenosine triphosphate(ATP) are allosteric inhibitors, whereas Guanosine diphosphate(GDP) and Adenosine diphosphate(ADP) are allosteric activators Hence, lowering of a energy charge(more ADP or GDP) accelerates oxidation of amino acids favouring formation of α-ketoglutarate that can be channeled towards TCA cycle for complete oxidation to provide energy
Slide 11-

Transdeamination Since majority of transamination reaction is α-ketoglutarate is acceptor keto acid forming glutamate, that is oxidatively deaminated in liver by glutamate dehydrogenase forming α-ketoglutarate and ammonia Conversion of α-amino nitrogen to ammonia by concerted action of GDH is termed as ‘transdeamination’ Thus transamination and deamination are coupled process though they occur at distant places
Slide 12-

GLUCOSE AND ALANINE CYCLE It is interorgan cycle that piggybacks on Cori cycle and accomplish net transport of nitrogen from muscles and other peripheral tissue to liver Pyruvate produced isn’t reduced to lactate (as in cori cycle) but transaminated to alanine which is transported to liver In liver transamination is reversed and pyruvate is converted to glucose by glycogenesis releasing glucose in bloodstream
Slide 13-

Nitrogen transport by Glutamine Glutamine is most abundant amino acid and is significant as nitrogen and amino acid carrier It brings net transfer of nitrogen from peripheral tissue to liver in exchange of glutamate The enzyme involved are transaminase, glutamate dehydrogenase, glutamate synthetase and glutaminase.
Slide 14-

Fate of carbon skeleton The carbon skeleton is the α-keto acid remaining after removal of ammonia from amino acid. It have following fates- Biosynthesis of non-essential amino acid by transamination with glutamic acid Converted into 7 common metabolites:- pyruvate, acetyl-CoA, acetoacetate, α-ketoglurate, succinyl-CoA, fumurate, oxaloacetate that are precursors to glucose or citric acid cycle intermediates The carbon skeletons of amino acids enter the citric acid cycle through five intermediates: acetyl-CoA, α-ketoglutarate, succinyl-CoA, fumarate, and oxaloacetate
Slide 15-

Classification of amino acid based on metabolic pathway
Slide 16-

6 Amino acid degraded to pyruvate Alanine- on direct transanimation Cysteine- in two step, one removes sulphur other transanimation Serine- concerted to pyruvate by serine dehydratase both β-hydroxyl and α-amino acid are removed in it Tryptophan- cleaved into alanine then pyruvate Glycine- conveted into serine via addition of hydroxymethyl group than to pyruvate Threonine- converted to2-amino-3-ketobutyrate than glycine and at last pyruvate
Slide 17-

ppt slide no 17 content not found
Slide 18-

7 Amino acid degraded to acetyl CoA and acetoacetal CoA Tryptophan-breakdown is most complex, portions of tryptophan (four of its carbons) yield acetyl-CoA via acetoacetyl-CoA Some of the intermediates in tryptophan catabolism are precursors for the synthesis of other biomolecules including nicotinate, a precursor of NAD and NADP in animals; serotonin, a neurotransmitter in vertebrates etc Lysine Phenylalanine- and its oxidation product tyrosine are degraded into two fragments, one converts to acetoacetate which is converted to acetyl-CoA, and other to fumarate both of which can enter the citric acid cycle Leucine Isoleucie- Final step of leucine, lysine and tryptophan resembles step in oxidation of fatty acid Threonine
Slide 19-

ppt slide no 19 content not found
Slide 20-

5 Amino acid degraded to α- ketoglutarate Proline-its cyclic structure is opened by oxidation of the carbon distant from the carboxyl group creating Schiff base, whose hydrolysis form a linear semialdehyde which is further oxidized at the same carbon to produce glutamate Glutamine- converts to glutamate by donating its amide group to aceptor b y action of glutaminase or other enzymes Glutamate-Transamination or deamination of glutamate produces α-ketoglutarate Arginine- is converted to ornithine which is transanimated to glutamate γ-semialdehyde which then converted to glutamate Histidine- its conversion to glutamate occur in multiple step
Slide 21-

ppt slide no 21 content not found
Slide 22-

4 Converted to succinyl-CoA Methionine-donates its methyl group to possible acceptor through S-adenosylmethionine and 3 of its 4 carbon converted to propionate of propionyl-CoA, a precursor of succinyl-CoA. Isoleucine -undergoes transamination, followed by oxidative decarboxylation of the resulting α-keto acid. The remaining five-carbon skeleton is further oxidized to acetyl-CoA and propionyl-CoA. Valine-undergoes transamination and decarboxylation, then a series of oxidation reactions that convert the remaining four carbons to propionyl-CoA Threonine-is also converted in two steps to propionyl-CoA Propionyl-CoA derived from these three amino acids is converted to succinyl-CoA via series of step
Slide 23-

ppt slide no 23 content not found
Slide 24-

Branched chain amino acid degradation Valine, Isoleucine, Leucine are BCAA that are oxidized as fuel mainly in muscles, kidney, brain tissue and adipose Oxidation of them are similar Oxidized to valine to succinyl-CoA- Glucogenic Isoleucine to succinyl-CoA and acetyl-CoA- gluco and ketogenic Leucine to acetyl CoA- ketogenic
Slide 25-

Aspargine And Asparate Degradation Their carbon skeletons enter the citric acid cycle as malate in mammals or oxaloacetate in bacteria. The enzyme asparaginase catalyzes the hydrolysis of asparagine to aspartate, which undergoes transamination with α-ketoglutarate to yield glutamate and oxaloacetate The oxaloacetate is converted to malate in the cytosol and then transported into the mitochondrial matrix through the malate–α-ketoglutarate transporter in mammals In bacteria oxaloacetate produced in the transamination reaction can be used directly in the citric acid cycle
Slide 26-

Research paper Inhibition Of Amino Acid Metabolism Selectively Targets Human Leukemia Stem Cells by- Courtney L. Jones1, Brett M. Stevens1, Angelo D'Alessandro1,2, Julie A. Reisz2, Rachel Culp-Hill2, Travis Nemkov2, Shanshan Pei1, Nabilah Khan1, Biniam Adane1, Haobin Ye1, Anna Krug1, Dominik Reinhold3, Clayton Smith1, James DeGregori1,2, Daniel A. Pollyea1, and Craig T. Jordan1
Slide 27-

Overview By studying the metabolome of human acute myeliod leukemia (AML) we found that amino acid metabolism(AAM) increases in the leukemia stem cell(LSC) LSC obtained from de novo AML patient rely on amino acid for oxidative phosphorylation and survival So pharmacological inhibition of AAM can cause reduced oxidative phosporylation (OXPHOS) and causes death hence, drugs that target AAM vulnerability can be used(like Venetoclax and azacitidine) LSC obtained from relapsed AML patient can compensate their AAM through increased fatty acid metabolism
Slide 28-

Introduction Conventional chemotherapy of AML patient can cause relapse It was found that cancer stem cells (CSCs) dependent on OXPHOS and have low glycolytic reserves compare to mature cells. Increased level of OXPHOS in CSCs can promote chemotherapy resistant LSCs in addition to above show specific metabolic properties like low level of reactive oxygen species, increased branched chain amono acid metabolism etc. these unique metabolic properties can be used to improve therapy for AML patients In this research it was demonstrated that inhibition of OXOPHOS is key determinant of LSC eradiction
Slide 29-

Result In LSC 39 metabolites were more in amount than AML blasts including 16 amino acids, 5 glutathione homeostasis metabolites and 2 TCA cycle intermediates which all are related to AAM LSC show high uptake and utilization of amino acid than AML blasts particularly for Glutamine, Glutamate and proline Amino acid depletion causes decreased colony formation by LSCs while AML blasts and HSPCs showed no effect. LSCs viability wasn’t much effected by the other metabolites in comparison to amino acid LSCs is selectively sensitive to loss of amino acid as they are less metabolically flexible BCL2 inhibition may reduce the AAM suppressing OXOPHOS. BCL2 inhibitors venetoclax with azacitidine reduce AAM and also amino acid uptake in LSCs is mechanism for LSCs eradication Relapse LSCs escape amino acid loss by increasing fatty acid metabolism
Slide 30-

Conclusion
Slide 31-

ppt slide no 31 content not found