3. BIOSYNTHESIS OF AMINO ACIDS Valine Isoleucine Leucine Threonine Lysine Methionine Tryptophane Phenylalanine Histidine These amino acids are not synthesized in human cells. Therefore, they are nutritionally essential amino acids. Their carbon sceleton can not be synthesized by human cells. Histidine is synthesized in a limited amount by intestinal bacteria, therefore, it is semi-essential nutritionally. Arginine is synthesized in the urea cycle, but the rate is insufficient to meet the need during growth. However, it is also considered as semi-essential amino acid. Amino acids are the precursors of several biologically active compounds! Glutamate and glycine are, for example, neurotransmitters!

4. BIOSYNTHETIC FAMILIES OF AMINO ACIDS IN PLANTS AND IN HUMAN CELLS Pyruvate Ribose 5-phosphate Oxaloacetate Aspartate Histidine AlanineValine Leucine Threonine AsparagineMethionine Lysine Isoleucine 3-Phosphoglycerate -Ketoglutarate Phosphoenolpyruvate + Erythrose 4-phosphate Serine Glutamate Phenylalanine Tryptophane Glutamine Proline Arginine Cystein Glycine Tyrosine

5. THE BIOSYNTHESIS OF NUTRITIONALLY NON-ESSENTIAL AMINO ACIDS Their carbon sceleton can be synthesized from the intermediates of the citric acid cycle or glycolysis from other amino acids Their NH2-group is obtained from glutamate (in most cases with the help of specific transaminases) L-glutamate dehydrogenase plays a central role in the biosynthesis of amino acids, as well, since it can incorporate NH3 into -ketoglutarate. -ketoglutarate oxaloacetate pyruvate phosphoglycerate

8. 1, The biosynthesis of glutamatefrom -ketoglutarate: Two enzymes contribute to glutamate production: a, glutamate dehydrogenase b, transaminases

9. 2, The biosynthesis of glutamine from glutamate: Glutamine synthase is the other enzyme which can incorporate NH3 in order to save it for organic compounds Glutamine is a NH2-group donor: for the purine-ring, for the pirimidine ring for the NH2-side groups of nucleotides for aminosugars for asparagine

10. 3, The biosynthesis of arginineandproline from glutamate: glutamate glutamate -  - semialdehyde slow rapid ornithineproline arginine urea cycle (semiessential)

14. 4, The de novo synthesis ofornithine: Synthesis of ornithine is an anaplerotic reaction of urea cycle in the absence of dietary arginine glutamate urea ornithine carbamoyl phosphate arginine dietary arginine urea cycle - NH2 In the absence of dietary arginine, arginine is used for protein synthesis and ornithine is the precursor of polyamines, the amount of ornithine would be decreased in the urea cycle without anaplerotic reaction The de novo synthesis of ornithine is slow (rate limiting), therefore, arginine is semi-essential.

15. 5, The biosynthesis of aspartatefrom oxaloacetate: COOH CH2 O = C - COOH COOH CH2 NH2 - C - COOH transaminase glutamate H oxaloacetate aspartate -ketoglutarate aspartate is an NH2-group donor for the synthesis of purine-ring for the synthesis of adenylate in the urea cycle aspartate is a precursor of the pyrimidine ring

16. 6, Formation of asparaginefrom aspartate: CONH2 CH2 NH2 - C - COOH COOH CH2 NH2 - C - COOH ATP + H2O AMP + PPi glutamine H H asparagine aspartate glutamate Enzyme: asparagine synthetase

17. 7, The biosynthesis of alaninefrom pyruvate: CH3 C NH2 COOH CH3 C = O COOH transaminase glutamate pyruvate alanine -ketoglutarate

18. 8, Formation of serinefrom phosphoglycerate: COOH H2N - CH CH2 – O – PO32+ COOH HC - OH CH2 – O – PO32+ phospho -serine phospho -glycerate H2O Pi NAD+ NADH + H+ phospho- glycerate dehydrogenase phosphatase transamination COOH H2N - CH CH2 – OH COOH C = O CH2 – O – PO32+ serine phosphopyruvate Serine is a precursor for: glycine, cystein and phospholipids

19. 9, Formation of glycinefrom serine: H2N – C - COOH CH2 – OH H serine tetrahydrofolic acid (FH4) N5,N10-methylene-FH4 H2O H2N – CH2 - COOH glycine

20. 10 5

21. Conversion of one-carbon units attached to tetrahydrofolate 5 5 5 Ser Gly NADH + H+ N H N N 10 10 10 NAD+ N H N N CH3 H2C N5-methyl-FH4 N5,N10-methylene-FH4 tetrahydrofolate H C=O OH NADP+ NADPH + H+ ATP ADP + Pi formiate 5 H2O H+ 5 N N 10 10 N H N H C O = C - H N5,N10-methenyl-FH4 N10-formyl-FH4

22. The metabolism of glycine The major pathway of degradation: glycine cleavage complex NH2 – CH2 – COOH CO2 NH3 THF (FH4) N5,N10-methylene-FH4 active C1

23. „nonketotic” hyperglycinemia: - the glycine cleavage complex is deficient - mental deficiency and many patients do not survive infancy Glycine is an „inhibitory” neurotransmitter Glycine is a precursor for purine nucleotides porphyrins creatine glycine conjugates different drugs are conjugated by glycine in the course of detoxication process

24. 10, Formation of tyrosinefrom phenylalanine: OH phenylalanine hydroxylase tyrosine CH2 NH2 – CH – COOH CH2 NH2 – CH – COOH phenylalanine melanine (pigment) DOPA Dopamine Norepinephrine Epinephrine Fumarate + acetoacetate Phenylalanine hydroxylase Deficiency: PHENYLKETONURIA

25. 11, Formation of cysteinefrom serine: The carbon skeleton of cysteine is derived from serine and the SH-group is derived from the sulphur of methionine (methinonine is nutritionally essential) The degradation process of methionine yields homocysteine

27. CYSTATION SYNTHASE DEFICIENCY Hyperhomocysteinemia and atherosclerosis excess homocysteine can form hymocysteine thiolactone, a highly reactive compound CH2 CH2 S H2N – CH – C = O Homocysteine thiolactone reacts with free amino groups in low density lipoprotein (LDL) and causes them to aggregate and be endocytosed by macrophages. The lipid deposits form atheromas About 25% of patients with atherosclerosis who exhibit none of the other risk factors have been found to be deficient in cystatione synthase!!

28. vitamine B12 DEVLIN

29. 12, Formation of taurinefrom cysteine: sulfinoalanine decarboxylase cysteine dioxygenase. Taurine is conjugated via its amino terminal group (bile acids) Neurotransmission, long-term potentiation (LTP) in the striatum/hippocampus Membrane stabilization, Taurine and cats Taurine is an essential dietary requirement for feline health, since cats cannot synthesize the compound. The absence of taurine causes a cat's retina to slowly degenerate, causing eye problems and (eventually) irreversible blindness — a condition known as central retinal degeneration (CRD),[