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Fate of absorbed amino acids

Fate of absorbed amino acids. Enter in the formation of A.A. pool. AA pool. ~ 80 % in muscles ~ 10 % in liver ~ 5 % in kidney ~ 5 % in blood Definition: AA POOL It include the free a.as distributed throughout the body

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Fate of absorbed amino acids

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  1. Fate of absorbed amino acids Enter in the formation of A.A. pool

  2. AA pool ~ 80 % in muscles ~ 10 % in liver ~ 5 % in kidney ~ 5 % in blood • Definition: AA POOL It include the free a.as distributed throughout the body • The a.a. pool contains 100 gm a.as.50% of these a.as are in the form of glutamate & glutamine (Why?) • In contrast to the amount of protein in the body (about 12 Kg in 70 Kg man), the a.a. pool is small (only 100 gm) AA pool is not reserve !! There is not a specific protein reserve in human body in contrast to saccharides (liver glycogen) and lipids (adip. tissue) !!

  3. Overall metabolism of proteins • All proteins in the body are continuously degraded (metabolized) and newly synthesized • Free AA from food, tissue proteins and non-essential AA from synthesis , make AA pool • AA pool is used for: i. New body proteins ii. Specialized products (amines, NO, porphyrines, NA bases ...) iii. Catabolic proceses (energy gain)

  4. ►SOURCES & FATE OF THE AA. POOL: Non essential a.a.s synthesized in the body Diatery proteins Tissue proteins a.a.s Amino acid pool Anabolism Catabolism(Deamination) Synthesis of Fate of deamination products Proteins Other nitrogenous compounds α- keto acid Ammonia ►Aminosugars ►Nitrogenous bases of phospholipids ►Purines & pyrimidines ►Neurotransmitters ►Niacin ►Creatine ►Heme Krebs cycle ►Tissue proteins ►Plasma proteins ►Enzymes ►Some hormones ►Milk Ketone bodies Synthetic pathway Catabolic pathway glucose CO2+H2O +ENERGY Non essential a.a.synthesis Excreted in urine glutamine Urea

  5. GENERAL STRATEGY • · Removal of N from amino acid by transamination(generally first or second step of amino acid catabolic pathways) and collection of N in glutamic acid • ·Deaminationof glutamic acid with release of NH4+ byglutamate dehydrogenase • Collection of N in glutamine or alanine for delivery to liver • ·Removal of NH4+ by : • i. secretion; or • ii. Conversion to urea or other less toxic form.

  6. TRANSAMINATION ►α-ketoglutarate & glutamate are often involved in transamination reactions Coenzyme: PLP (Pyridoxal phosphate)

  7. In transaminations, nitrogen of most AAisconcentratedin glutamate Glutamate then undergoes oxidative deamination and releases free ammonia NH3

  8. DEAMINATION . ► α- keto glutarate ◄ α- a.a. ◄ ► NH3 ► NAD(P)H+H GLUTAMATE TRANSAMINASE GLUTAMATE DEHYDROGENASE NAD(P) ► ► H2O α- keto acid Glutamic acid ◄ ◄

  9. Intracellular localization Transamination  glutamate cytosol mitochondria Glutamate Dehydregenase glutamate NH3 urea synthesis cytosol Glu + NH3 Gln

  10. Dehydrogenation deamination of glutamate isa reversible reaction NAD(P)+ 2-iminoglutarate glutamate main source of ammonia in cells 2-oxoglutarate GMD = glutamate dehydrogenase

  11. Deamination products α- keto acid NH3

  12. ►IMPORTANCE OF OXIDATIVE DEAMINATION glutamate dehydrogenase enzyme is the only enzyme by which a.a. undergoes oxidative deamination in the mammalian tissue. Oxidative deaminationby glutamate dehydrogenase is an essential component ofTRANSDEAMINATION.

  13. ■Diagnosticvalue of transamination : Transaminases are normally intracellular enzymes. They are elevated in the blood when damage to the cells producing these enzymes occurs. * Increase level of both ALT & AST indicates possible damage to the liver cells. * Increase level of AST ALONE suggests damage to heart muscle , skeletal muscle or kidney.

  14. Q. Which cofactor is used by aminotransferases?

  15. Pyridoxal phosphate

  16. Q. What are two main sources of ammonia in human body?

  17. Two main sources of ammonia in body ! • Dehydrogenation deamination of glutamatein cells of most tissues • Bacterial fermentation of proteins in large intestineammonia diffuses freely into portal blood  portal blood has high concentration of NH3NH3 is eliminated by liver (under normal cond.) !

  18. Three ways of ammonia detoxication a Equivalent of 3 ATP (compare respiratory chain).

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