6. Glutamate collects and delivers free ammonia to the liver Free ammonia is produced in tissues(e.g by the direct deamination of Ser and Thr deamination of nucleotides) and is toxic to animals, thus need to be transported to the liver by first converting to a nontoxic compound, GIn Glutamine synthetase catalyzes the two-step addition of ammonia to Glu to yield Gln, with ATP consumed to activate the y-Cooh This reaction also represents how fixed nitrogen in bacteria enter biomolecules: GIn is the source of amino groups in a variety of biosynthetic reactions
6. Glutamate collects and delivers free ammonia to the liver • Free ammonia is produced in tissues (e.g., by the direct deamination of Ser and Thr, deamination of nucleotides) and is toxic to animals, thus need to be transported to the liver by first converting to a nontoxic compound, Gln. • Glutamine synthetase catalyzes the two-step addition of ammonia to Glu to yield Gln, with ATP consumed to activate the g-COOH. • This reaction also represents how fixed nitrogen in bacteria enter biomolecules; Gln is the source of amino groups in a variety of biosynthetic reactions
NH OOC—CH2-CH2-CH-COO L-Glutamate ATP glutamine synthetase ADP NH3 O-P-0-C-CH2-CH2-CH-COO Glutamyl phosphate NH4 glutamine synthetase NH C-CH -CH2-CH-CO0 H2N L-Glutamine
The pyruvates and amine groups are transported to liver in the form ot Ala ruvate is an abundant product from muscle glycolysis and can take an amino group (from glu) to form Ala(alternatively, be reduced to lactate Alanine once gets to liver will then transfers it's s amino group to a-ketoglutarate or oxaloacetate to reform pyruvate. ruvate is reconverted to glucose in liver via the gluconeogenesis pathway, which will be transported back to muscle for energy supply. This is called alanine-glucose cycle, complementing the Cori cycle for liver to continuously provide 、; glucose to vigorously contracting skeletal muscles
7. The pyruvates and amino groups are transported to liver in the form of Ala • Pyruvate is an abundant product from muscle glycolysis and can take an amino group (from Glu) to form Ala (alternatively, be reduced to lactate). • Alanine once gets to liver will then transfers it’s amino group to a-ketoglutarate or oxaloacetate to reform pyruvate. • Pyruvate is reconverted to glucose in liver via the gluconeogenesis pathway, which will be transported back to muscle for energy supply. • This is called alanine-glucose cycle, complementing the Cori cycle for liver to continuously provide glucose to vigorously contracting skeletal muscles
The alanine. glucose eyc Muscle: ATP produced by glycolysis for rapid contraction Blood A glucose Pyruvate TP AT Liver: ATP used in synthesis of glucose(gluconeogenesis during recovery
Ala Ala Ala Pyruvate Pyruvate The alanineglucose cycle
8. GIn and Gl releases NHAt in liver mitochondria The glutaminase in liver mitochondria catalyzes the conversion of GIn to Glu, releasing NH4(from the side chain amide of gIn). The glutamate dehydrogenase(a hexameric allosteric enzyme) there catalyzes the oxidative electrons collected by either NAD+ or NADPx-ed deamination of Glu, releasing NH*. with releas Glutamate dehydrogenase is allosterically activated a lowering of the energy charge accelerates th pe by ADP and GDP, but inhibited by ATP and G e oxidation of amino acids 2
8. Gln and Glu releases NH4 + in liver mitochondria • The glutaminase in liver mitochondria catalyzes the conversion of Gln to Glu, releasing NH4 + (from the side chain amide of Gln). • The glutamate dehydrogenase (a hexameric allosteric enzyme) there catalyzes the oxidative deamination of Glu, releasing NH4 + , with released electrons collected by either NAD+ or NADP+ . • Glutamate dehydrogenase is allosterically activated by ADP and GDP, but inhibited by ATP and GTP, i.e., a lowering of the energy charge accelerates the oxidation of amino acids