L-58 Nitrogen Metabolism And Amino Acid Biosynthesis

Front 1

Glutamine synthetase (GS)

Back 1

Main regulatory enzyme of nitrogen metabolism.

Glutamate + ATP -> delta-glutamyl phosphate + ADP

delta-glutamyl phosphate + NH4+ -> glutamine + Pi

Prok - class 1 - 12 subunits 2x6

Euk - Class 2 - 10 subunits 2x5

Front 2

Regeneration of glutamate

Back 2

Plants use glutamate synthetase (GOGAT).

All use glutamate dehydrogenase to create glutamate from alpha ketoglutarate.

Front 3

Regulation of glutamine synthetase

Back 3

Alanine, Glycine, and 6 end products of glutamine metabolism (Glucosamine-6-Phosphate, Histidine, Tryptophan, AMP, and Carbamoyl phosphate) are allosteric inhibitors.

Adenylation at Tyr397 inhibits enzymatic activity (by adenylyl transferase)

Uridylated PH activates transcription of GS.

Totally, GS activity is low when glutamine is high and high when glutamine is low and alpha ketoglutarate/ATP are available.

Front 4

Glutamine Amidotransferases

Back 4

Transfer amino groups from glutamine amide.

Have glutamine binding and NH3-acceptor domain.

Cys in glutamine-binding domain is nucleophile and cleaves amide of glutamine, forming glutamyl-enzyme intermediate.

NH3 is transferred to NH3-acceptor domain.

Front 5

Alphaketoglutarate

Back 5

Alpha ketoglutarate -> glutamate -> glutamine, ornithine, arginine

Ornithine -ornithine delta-aminotransferase-> proline

Front 6

Ornithine-delta-aminotransferase deficiency

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AR. Unable to produce proline. Myopia in childhood advancing to night blindness and full blindness.

Front 7

3-Phosphoglycerate

Back 7

3-PG -> serine -> glycine - requires tetrahydrofolate and produces N5 N10-methylenetetrahydrofolate. PLP cofactor.

Serine + homocysteine -> cysteine

Defect in cystiethione beta-synthase leads to homocysteine buildup, causing vascular disease.

Serine and glycine are precursors for cancer cell growth metabolism and lower cell's antioxidative capacity.

Front 8

Pyruvate

Back 8

Alanine - transamination from glutamate

Front 9

Oxaloacetate

Back 9

Asparate - transamination from glutamate

Asparagine - amidation of aspartate by glutamine.

Front 10

Molecules derived from glycine

Back 10

Glycine + succinyl coA -> ALA ->>> Heme

Front 11

Creatine/Phosphocreatine

Back 11

Glycine + Arginine + Methionine

Front 12

Glutathione

Back 12

Glutamine + Cysteine + Glycine

Front 13

Neurotransmitters

Back 13

Tyrosine -> Catecholamines (NE, E, Dopamine)

Glutamate -> GABA

Tryptophan -> Serotonin

Front 14

Nitric Oxide

Back 14

Arginine -NO Synthase-> Hydroxyarginine -NO Synthase-> NO + Citrulline

Front 15

Polyamines

Back 15

Arginine + Met

Arginine -> Ornithine -ornithine decarboxylase-> Putrescine -adoMet-> Spermidine -adoMet-> Spermine

Front 16

African Sleeping Sickness

Back 16

Treat with ornithine decarboxylase inhibitor - ornithine decarboxylase rapidly overturns in humans but not in protists.