Medical Biochemistry II PDF

Medical Biochemistry II Synthesis of non-essential amino acids from TCA intermediates and essential that feed into TCA cycel SMU - Internal Data Student Learning outcomes SMU - Internal Data AA related through glutamate All can be synthesized from glucose except? These aa contain carbons that can be...

Medical Biochemistry II Synthesis of non-essential amino acids from TCA intermediates and essential that feed into TCA cycel SMU - Internal Data Student Learning outcomes SMU - Internal Data AA related through glutamate All can be synthesized from glucose except? These aa contain carbons that can be reconverted to glutamate SMU - Internal Data 1. Glutamate The five carbons of glutamate are derived from a-ketoglutarate either by transamination or by the glutamate dehydrogenase reaction When glutamate is degraded, it is likewise converted back to aketoglutarate NADPH NH4+ Alphaketoglutarate NADP+ Glutamate Glutamate dehydrogenase Or transamination reaction NADH NH4+ SMU - Internal Data Alphaketoglutarate NAD+ Glutamate Glutamate dehydrogenase 2. Glutamine Glutamine is produced from glutamate by glutamine synthetase Glutamine is reconverted to glutamate by a different enzyme, glutaminase, which is particularly important in the kidney since it produces ammonia that enters the urine and aids in the excretion of metabolic acids such as NH3+ H+ è NH4+ SMU - Internal Data Liver and kidney 3. Proline The synthesis and degradation of proline use different enzymes even though the intermediates are the same Proline Proyl hydroxylase Vitamin C hydroxyproline Hydroxyproline is only formed after proline has been incorporated into collagen by the prolyl hydroxylase system which uses molecular oxygen, iron, a-ketoglutarate, and ascorbic acid (vitamin C) Hydroxyproline is not incorporated into proteins but makes up 4% of all aa in animal tissues due to importance in collagen stability SMU - Internal Data 3. Proline (and ornithine) synthesis and degradation Glutamate Ornithine Ornithine aminotransferase Delta 1 – pyroproline 5carboxylate oxidase reductase tautamerization Glutamate/B6 Etc. Glutamate-gamma-semi aldehyde (GSA) NAD+ DH NADH Proline SMU - Internal Data Glutamate 4. Arginine Connecting arginine and glutamate: Arginine is synthesized from glutamate via glutamate semialdehyde, which is transaminated to form ornithine, an intermediate of the urea cycle SMU - Internal Data 4. Arginine degradation (and glutamate and proline and ornithine) agrinase Arginine urea Urea cycle Glutamate Ornithine Ornithine aminotransferase Delta 1 – pyroproline 5carboxylate oxidase reductase tautamerization Glutamate/B6 Etc. Glutamate-gamma-semi aldehyde (GSA) NAD+ DH NADH SMU - Internal Data Proline Glutamate Histidine Although histidine cannot be synthesized in humans, five of its carbons form glutamate when it is degraded Histidine is converted to formiminoglutamate (FIGLU) The subsequent reactions transfer one carbon of FIGLU to the FH4 pool and release NH4+ and glutamate SMU - Internal Data Amino Acids Related to Oxaloacetate (Aspartate and Asparagine) Aspartate is produced by transamination of oxaloacetate (also major degradation route) Readily reversible Asparagine is formed from aspartate by a reaction in which glutamine provides nitrogen SMU - Internal Data 1. Aspartate – AA that forms fumerate Although the major route for aspartate degradation involves its conversion to oxaloacetate, carbons from aspartate can form fumarate in the urea cycle. This reaction generates cytosolic fumarate, which must be converted to malate (using cytoplasmic fumarase) for transport into the mitochondria for oxidative or anaplerotic purposes. Note: defects in fumarate hydratase have been linked with cancers: leiomyoma and renal cysts SMU - Internal Data 2. Tyrosine: amino acid that forms fumerate Phenylalanine is hydroxylated to form tyrosine by a mixed function oxidase, phenylalanine hydroxylase (PAH), which requires molecular oxygen and tetrahydrobiopterin Tetrahydrobiopterin can be synthesized in the body from GTP SMU - Internal Data 2. Tyrosine Tyrosine is oxidized, ultimately forming acetoacetate and fumarate. Phenylalanine Phenylalanine hydroxylase BH4 Tyrosine BH4 Tyrosine hydroxylase L-Dopa Tyrosinase Dopaquinone Many steps Homogentisate Melanin Many steps Acetoacetate SMU - Internal Data Fumerate