Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry

Transcription

1 Amino Acids Metabolism ١

2 i Metabolism ٢

3 NH2 Structure It is α-amino acetic acid Nutrional Value It is non-essential amino acid Metabolic Fate It is glucogenic g amino acid ٣

4 Biosynthesis 1. From 2 and NH 3 2. From glyoxylic acid 3. From serine 4. From threonine 5. From choline 6. From hydroxy proline ٤

5 1- Biosynthesis from 2 and NH 3 N 5, N 10 methylene H 4 folate H 4 folate 2 + NH 3 H2 synthetase NADH.HH + NAD + ٥

6 2- Biosynthesis from glyoxylic acid H Glyoxylic Glutamic acid PLP Aminotransferase α ketoglutaric ٦

7 3- Biosynthesis from serine H 4 Folate methylene H 4 Folate H H2 H Serine Serine hydroxymethyl transferase ٧

8 4- Biosynthesis from threonine H H 3 H H Threonine Threonie aldolase + H 3 H Acetaldehyde ٨

9 5- Biosynthesis from choline H 3 H 3 N H H 3 holine 2H H 3 H 3 H 3 N H H 3 N H 3 H 3 Betaine aldehyde Betaine serine H 3 H 3 NH H 3 N monomethyl glycine (sarcosine) H 3 Dimethyl glycine ٩

10 6- Biosynthesis from hydroxy proline H H H oxidation H H H H N H H Hydroxy proline γ hydroxy glutamic γ semialdehyde H oxidation H H H γ hydroxy glutamic transamination transamination + Aldolase H H 3 Glyoxylic Pyruvic acid H H γ hydroxy α ketoglutamic ١٠

11 Biosynthesis 1. From 2 and NH 3 2. From glyoxylic acid 3. From serine 4. From threonine 5. From choline 6. From hydroxy proline ١١

12 Metabolic Fate 1. leavage to 2 and NH 3 2. Formation of glyoxylic li acid 3. Biosynthesis of serine 4. Synthesis of glucose 5. reatine and creatinrne synthesis 6. Synthesis of glutathione thi 7. Haeme biosynthesis 8. Synthesis of purine bases 9. Detoxication of benzoic acid 10. onjugation with bile acids 11. Incorporated in tissue proteins ١٢

13 1- leavage into 2 and NH 3 N 5, N 10 methylene H 4 folate H 4 folate synthetase NAD+ NADH.HH NH 3 ١٣

14 2- Formation of glyoxylic acid α ketoglutaric PLP Glutamic acid Aminotransferase H Glyoxylic Formic ١٤

15 3- Biosynthesis of serine methylene H 4 Folate H 4 Folate NH H NH 2 2 Serine hydroxymethyl transferase H Serine ١٥

16 4- Glucose synthesis dehydratse Serine dehydratse Pyruvic acid Serine hydroxymethyl transferase Glucose ١٦

17 5- Biosynthesis of reatine and creatinrne NH HN 2 NH H Arginine Transamidinase H HN H 2 N H HN H Guanidoacetic rnithine acid ١٧

18 HN HN Biosynthesis of reatine and creatinine NH 2 rnithine NH acid Kidney H H 2 H 2 N HN + H HN H i 2 Arginine Arginine NH N H 3 reatinine ١٨ P i +H 2 reatine phosphate HN NH P N H 3 Transamidinase Muscle reatine Kinase ADP S-Adenosyl methionine S-Adenosyl homocysteine ATP HN Guanidoacetic Guanidoacetate methyltransferase N H 3 Liver reatine

19 Blood level reatine and reatinine reatine mg/dl. reatinine mg/dl Urinary excretion Normally creatine is present in very small amount in urine. Normal urine creatinine levels: 1 2 g/24 hours reatinine excretion for each individual is constant reatinine coefficient Males: mg/kg/24 hours Females: mg/kg/ 24 hours reatinine learance Males: ml/minute Females: ml/minute ١٩

20 reatinuria Physiological causes In children In females: during pregnancy and after labour Prolonged administration of androgens Pathological causes Degenerative Muscular dystrophy. Myasthenia gravis. Acute poliomyelitis. l Hypogonadism Increase tissue catabolism Hyperthyroidism Starvation Diabetes mellitus Tumors ٢٠

21 7- Biosynthesis i of glutathione thi H H γ Glutamyl cysteine SH synthetase + H ysteine Glutamic acid ATP H 2 ADP+Pi NH H H SH γ Glutamyl cysteine Glutathione NH H H SH NH (γ Glutamyl cysteinyl glycine) H 2 2 ATP ADP+Pi ٢١

22 Functions of glutathione Glutathione protects red cells from haemolysis by H 2 2 It protects haemoglobin against oxidation by H 2 2 Glutatione has a role in an amino acid transport system It inactivates insulin in the liver. It maintains (-SH) group, which is important for the activity of many enzymes. It protects the B-cells of pancreas from the degenerative action of alloxan Glutathione acts as a hydrogen carrier ٢٢

23 H G-SH Glutathione peroxidase S G Selenium G-S-S-G + 2 H 2 Glutathione reducase NADP NADPH+H α chain 21 aa S S S S 7 19 β chain 30 aa SH SH SH SH Insulin + 4 G-SH Insulin Glutathione Transhydrogenase 2 G-S-S-G + 2 separate peptides ٢٣

24 7- Biosynthesis of Haeme Succinyl oa ٢٤ S oa + H H ALA synthetase PLP oash H H NH H α amino β ketoadepic acid H ALA synthetase 2 H 2 ALA dehydratase 2 H 2 δ aminolevulinic acid NH H Porphobilinogen

25 8- Biosynthesis i of purine bases N H N 3 N 4 N 7 9 N H 8 H ٢٥

26 9- Detoxication by conjugation oa.sh S.oA Benzoic acid ATP ADP+Pi Benzoyl oa S.oA Benzoyl oa + oa.sh NH Hippuric acid ٢٦

27 10 onjugation with bile acids H H H H H H H H holyl oa holic Acid S.oA + H oa.sh H H Na H NH Glycocoholic Acid K Na glycocoholate K glycocoholate henodeoxycholic h Acid henodeoxyholyl h l oa Glycochenodeoxycoholic Acid ٢٧

28 atabolic Fate 1. leavage to 2 and NH 3 2. Formation of glyoxylic acid 3. threonine cycle 4. succinate cycle ٢٨

29 1- leavage into 2 and NH 3 N 5, N 10 methylene H 4 folate H 4 folate synthetase NAD+ NADH.HH NH 3 ٢٩

30 2- Formation of glyoxylic acid α ketoglutaric PLP Glutamic acid Aminotransferase H Glyoxylic Formic ٣٠

31 3- threonine cycle Acetaldehyde H 3 H H H 3 H H Threonine Acetic acid H 3 Acetyl oa 2 H 3 oa.sh H 3 H α Amino β ketobutyric S.oA H 3 2 Aminoacitone i NH 3 Pyruvic acid H 3-2H Lactic acid H 3 H Glyoxal H H 3 H ٣١

32 4- succinate cycle H 2 GDP+Pi S oa Succinyl oa Succinate thiokinase GTP oa.sh ALAsynthetasese H PLP H oash H ALA synthetase α amino β ketoadepic acid xidation 2 H 2 δ aminolevulinic acid NH 3 H 2 α Ketoglutaric acid 2 Succinic i acid xida idation H α Ketoglutaraldehyde Haeme ٣٢ H Succinic semialdehyde

33 Inborn errors of glycine metabolism 1. Primary hyperoxaluria 2. Glycinuria ٣٣

34 Inborn errors of glycine metabolism 1. Primary hyperoxaluria Failure to metabolize glyoxylic acid normally ٣٤

35 Sources and fate of glyoxylic acid H Glyoxylic H- Formic acid xalic acid Hydroxy proline Urine ٣٥

36 Inborn errors of glycine metabolism 1. Primary hyperoxaluria Failure to catabolize glyoxylic acid normally Subsequent q oxidation of glyoxylic y to oxalic acid Increased excretion of oxalic acid in urine in the form of calcium oxalate This results in: Urolithiasis Nephrocalcinosis Early mortality from Renal failure Hypertension. ٣٦

37 2. Glycinuria i Inborn errors of glycine metabolism Excess excretion of glycine in urine y level in blood is normal A defect in renal tubular reabsorption of glycine xalate excretion in urine is normal. Tendency d of formation of oxalate urinary stones ٣٧

38 ٣٨

39 I B A ٣٩

40 I B A ٤٠