Amino Acid Metabolism (day-2). What to Know. What is the Metabolic Fate of Ammonium? How is Escherichia coli Glutamine Synthetase regulated? Understand general ways that organisms synthesize amino acids Know the definition of essential versus nonessential amino acids
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(a) The glutamine synthetase reaction. (b) The reaction proceeds by activation of the γ-carboxyl group of Glu by ATP, followed by amidation by NH4+.
NH4+ + HCO3- + 2ATP → H2N-COO-PO32- + 2ADP + Pi + 2H+
The subunit organization of bacterial glutamine synthetase.
(b) Molecular structure: note the pairs of metal ions (dark blue) that define the active sites.
Allosteric Regulation of Glutamine Synthetase
Covalent modification of GS: Adenylylation of Tyr-397 in the glutamine synthetase polypeptide via an ATP-dependent reaction by the converted enzyme adenylyl transferase.
Degree of adenylation, n, ~ GS activity so high [Gln] / [α-KG] ratio = cell nitrogen sufficiency and GS becomes adenylated and inactivated.
Essential vs Nonessential Amino Acids
1) 3 glycolytic pathway intermediates
Note: Plants and bacteria are capable of synthesizing all 20 of the amino acids illustrated in the figure; yet amino acid biosynthesis in animals is much more restricted due to the lack of many of the required enzymes.
Feedback inhibition plays a pivotal role modulating amino acid biosynthetic pathways
Glutamate-dependent transamination of α-keto acid carbon skeletons is a primary mechanism for amino acid synthesis.
Glutamate-dependent transamination of α-keto acid carbon skeletons is a primary mechanism for amino acid synthesis. The transamination of oxaloacetate by glutamate to yield aspartate and α-ketoglutarate is a prime example.
Aspartate biosynthesis via transamination of oxaloacetate by glutamate.
Asparagine biosynthesis from Asp, Gln, and ATP by asparagine synthetase. β-Aspartyladenylate is an enzyme-bond intermediate.
Biosynthesis of three nonessential amino acids (alanine, aspartate and asparagine) and six essential amino acids (methionine, threonine, lysine, isoleucine, valine and isoleucine) in E. coli involves two interconnected pathways utilizing pyruvate and oxaloacetate as precursors.
Metabolic degradation of the common amino acids
Glucogenic amino acids are shown in pink, ketogenic in blue
Aromatic amino acids are synthesized in plants, fungi and bacteria by a pathway involving formation of a hydrocarbon rain following the condensation of phosphoenolpyruvate and erythrose-4-phosphate.
Chorismate is a precursor to the three aromatic amino acids, tryptophan, tyrosine and phenylalanine.
Herbicides target chorismate
“Roundup Ready soybeans” via gene gun insertion of DNA
Amino Acids are Precursors to other Biomolecules
Precursor to several important molecules in metabolic signaling and neurotransmission including epinephrine and dopamine
Tyrosine is also the precursor to pigment molecules called melanins that are produced from dopaquinone
Phenylketonuriacs must be careful to avoid processed foods and beverages containing aspartame (aspartyl-phenylalanine methyl ester)
Phenylalanine hydroxylase gene located on chromosome 12– autosomal recessive genetic disease
Probability that two PKU carriers will have a child with the disease is 25%
frequency of carriers equals 2%, therefore, probability of a baby born with PKU by random chance equals one in 10,000
Albinism is another autosomal recessive disease
Defective gene = tyrosinase
tyrosinase deficiency results in loss of hair and skin pigments
The combination of symptoms of congenital erythropoieticporphyria, combined with common medieval practice of drinking animal blood as a treatment for human ailments may have accounted for the legend of vampires.