Presentation is loading. Please wait.

Presentation is loading. Please wait.

Amino Acid Metabolism Student Edition 6/3/13 version

Similar presentations

Presentation on theme: "Amino Acid Metabolism Student Edition 6/3/13 version"— Presentation transcript:

1 Amino Acid Metabolism Student Edition 6/3/13 version
Dr. Brad Chazotte 213 Maddox Hall Pharm. 304 Biochemistry Fall 2014 Web Site: Original material only © B. Chazotte

2 Goals Understand the relationship of nitrogen to carbon intermediary metabolism. Learn the Urea Cycle sequence, reactions, and products. Have an understanding of an overview of amino acid catabolism resulting in 7 basic products and the difference between ketogenic and glucogenic catabolism. Have an understanding of an overview of amino acid anabolism from basic precursors. Understand the concept of essential and nonessential amino acids in the diet of humans. Understand that many diseases can arise from errors in amino acid metabolism. Do NOT memorize any of the specific amino acid catabolic or anabolic pathways. They are for informational purposes only.

3 Nitrogen Pathways in Intermediary Metabolism
Plants . Matthews et al Figure 20.1

4 Dietary Amino Acids in Metabolism
“Excess dietary amino acids are not simply excreted but are converted to common metabolites that are precursors of glucose, fatty acids, ketone bodies – and are therefore metabolic fuels” Voet, Voet & Pratt 2008 p.732

5 Protein Synthesis & Degradation
Nutrient storage as protein; break proteins down in times of metabolic need (muscle a prime source) Eliminate accumulation of abnormal proteins that would harm the cell Permit the regulation of cellular metabolism by the elimination of unneeded enzymes and regulatory proteins. Voet, Voet & Pratt p.733

6 Catabolism

7 Cellular Protein Degradative Routes
Lysosomal - a cellular compartment at ~pH 5 containing hydrolytic enzymes (cathepsins). Degrade substances taken up by endocytosis. Recycle intracellular constituents enclosed within vacuoles. In “well nourished cells” protein degradation is nonselective. In starving cells a selective pathway is activated that imports and degrades proteins that contain the pentapeptide (Lys-Phe-Glu-Arg-Gln; KFERQ) e.g., in muscle and liver, but not brain. Ubiquitin-Based – ATP-based process independent of lysosomes. Proteins are marked for degradation by linking to ubiquitin.

8 Rx Involved in Protein Ubiquination
Proteasome Matthews et al Figure 20.10 Voet, Voet & Pratt 2013 Fig 21.2 Matthews et al Figure 20.11 Voet, Voet & Pratt 2013 Fig 21.4

9 Distinguishing Protein Lifetimes
The N-end Rule: N-terminal residues Asp, Arg, Leu, Lys & Phe half-life ~ 2-3 minutes Ala, Gly, Met, Ser Thr, & Val half-life > 20 hrs in eukaryotes (>10 prokaryotes) PEST proteins Proteins with segments rich in Pro, Glu, Ser, & Thr are rapidily degraded- these AA have sites that can be phosphorylated – thus targeting them for ubiquitination. Voet, Voet & Pratt 2013 Table 21.1

10 Some Cellular Processes Regulated by Protein Degradation
e.g,NF-κB –I κB system Berg, Tymoczko, & Stryer 2012 Table 23.3

11 Protein (“Macro”) Digestion in the Human Gastrointestinal Tract
Berg, Tymoczko, & Stryer 2012 Figure 23.1 Lehninger 2000 Figure 18.3

12 Amino Acid Catabolism: Overview
Amino acid degradation includes a key step of separating the amino group from the carbon skeleton. Lehninger 2004 Figure 18.1 Voet, Voet & Pratt 2013 Fig 21.6

13 Amino Acid Deamination
Transamination - most amino acids are deaminated by this process carried out by transaminases (aminotransferases). Amino group of amino acid is transferred (predominately) to -ketoglutarate Voet, Voet & Pratt 2013 Chap. 21 page 719 Oxidative Deamination – of glutamate by glutamate dehydrogenase yields ammonia and -ketoglutarate Voet, Voet & Pratt 2013 Chap. 21 page 722

14 Forms of Pyridoxal-5’-Phosphate
Needed by aminotransferases as a coenzyme. Voet, Voet & Pratt 2013 Fig 21.7

15 PLP-Dependent Enzyme Catalyzed Transamination Mechanism
Voet, Voet & Pratt 2013 Fig 21.8

16 Oxidative Degradation of Amino Acids
Occurs under three different circumstances in animals: During normal homeostasis Protein-rich diet Starvation or uncontrolled diabetes mellitus 1) Lehninger 2000 Chapter 18

17 Glutamate Dehydrogenase (Oxidative Deamination)
A mitochondrial enzyme yielding ammonia and -ketoglutarate It is the only enzyme that can accept either NAD+ or NADP+ as a coenzyme G° = ~30 kJ mol-1 Due to the high toxicity of ammonia – it is important that under physiological conditions G ≈ 0, i.e. at equilibrium. mammalian liver Lehninger 2000 Figure 18.7

18 Ammonia Transport to Liver for Urea Synthesis
Matthews et al Figure 20.14 Lehninger 2000 Figure 18.8

19 Urea Cycle

20 Urea Cycle Enzymes Carbamoyl Phosphate synthetase (mitochondrion)
Ornithine transcarbamoylase (mitochondrion) Argininosuccinate synthetase (cell cytosol) Argininosuccinase (cell cytosol) Arginase (cell cytosol)

21 Overall Urea Cycle Reaction
Voet, Voet & Pratt 2013 Chap 21 p 723

22 Urea Cycle & Feeder Reactions
Voet, Voet & Pratt 2013 Fig 21.9 Lehninger 2000 Figure 18.9

23 Urea Cycle Diagram Lehninger 2000 Figure 18.9

24 Nitrogen-acquiring reactions in Urea Synthesis
Lehninger 2004 Figure 18.11

25 Linking the Urea & Citric Acid Cycles “ Krebs ‘Bicycle’ ”
Lehninger 2004 Figure 18.12

26 AA Degradation to 1 of 7 Common Intermediates
Voet, Voet & Pratt 2013 Fig 21.13

27 Glucogenic vs Ketogenic Amino Acid Degradation
Glucogenic - degradation lead to glucose precusors: pyruvate, α-ketoglutarate, succinyl-CoA, fumarate or oxaloacetate Ketogenic – degradation leads to fatty acids or ketone body precursors: acetyl-CoA or acetoacetate Some amino acids are gluco- and keto-genic

28 Examples of a Few Disorders of Human Amino Acid Catabolism
PKU Tyrosimenia I, II, or III Rx 5, 2, or 4- respectively {side 35} Lehninger 2000 Table 18.2

29 Anabolism

30 Human Essential & Non-Essential Amino Acid
Voet, Voet & Pratt 2013 Table 21.3

31 Amino Acid Biosynthetic Families
CAC Glycolysis PP Glycolysis PP CAC Lehninger 2000 Table 22.1

32 Metabolic Relationships Among Amino Acids Derived from Citric Acid Cycle Intermediates

33 Biosynthesis of Non-Essential Amino Acids
With the exception of tyrosine, all the nonessential amino acids come from one these four metabolic intermediates: pyruvate, oxaloacetate, α-ketoglutarate, and 3-phosphoglycerate.

34 End of Lecture Materials

35 Supplementary Material on Amino Acid Catabolism
This material will NOT be on any test and is for informational purposes only.

36 Pathways for Ala, Cys, Gly, Ser & Thr to Pyruvate
Voet, Voet & Pratt 2008 Fig 21.14

37 Serine Dehydratase Voet, Voet & Pratt 2008 Fig 21.15

38 Pathways for Arginine, Glutamate, Glutamine, Histidine & Proline to -ketoglutarate
Voet, Voet & Pratt 2008 Fig 21.17

39 Methionine Degradation
Voet, Voet & Pratt 2008 Fig 21.18

40 TetraHydroFolate 2-State Reduction of Folate to THF
Voet, Voet & Pratt 2008 Table 21.2, Fig 21.19

41 Branched-Chain AA Degradation
. Voet, Voet & Pratt 2008 Fig 21.21

42 Mammalian Liver Lysine Degradation
Saccharopine dehydrogenase Saccharopine dehydrogenase aminoadipate semialdehyde dehydrogenase Sminoadipate amino- transferase Α-keto acid dehydrogenase Glutaryl-CoA dehyd. decarboxylase Enoyl-CoA dehydratase Β-hydrozyacylCoA dehydrogenase HMG-CoA synthase HMG-CoA lyase 1 Voet, Voet & Pratt 2008 Fig 21.22

43 Tryptophan Degradation
formamidase Tryptophan-2,3- dioxygenase Kynureninase-3- monooxygenase Kynureninase Voet, Voet & Pratt 2008 Fig 21.23

44 Phenylalanine Degradation
Phenylalanine hydroxylase Tyrosine aminotransferase p-hydroxyphenyl pyruvate dioxygenase Homogentisate dioxygenase fumarylacetoacetase Voet, Voet & Pratt 2008 Fig 21.24

45 Supplementary Information of Amino Acid Anabolism
The information in the slides hereafter is for informational purposes only, if you are interested, and will NOT be part of any test. Amino acid degradative and biosynthetic pathways are sites for a significant number of illnesses and/or genetic defects.

46 Alanine, Aspartate, Glutamate, Asparagine & Glutamine Syntheses (Non-essential)
Voet, Voet & Pratt 2008 Fig 21.27

47 Glutamate “Family” Syntheses: Arginine, Ornithine & Proline
γ-glutamyl kinase Glutamate dehydrogenase Path in mammals Pyrroline carboxylate reductase Voet, Voet & Pratt 2008 Fig 21.30

48 3-Phosphoglycerate  Serine Conversion
3-phosphoglycerate dehydrogenase Phosphoserine aminotransferase Phosphoserine phosphotase Voet, Voet & Pratt 2008 Figure 21.31

49 Biosynthesis of Essential Amino Acids

50 Biosyntheses of Aspartate “Family”: Lysine, Methionine, & Threonine
Voet, Voet & Pratt 2008 Fig 21.32

51 Biosyntheses of the Pyruvate “Family”: Isoleucine, leucine & Valine
Voet, Voet & Pratt 2008 Figure 21.33

52 Biosyntheses of Phenylalanine, Tryptophan, & Tyrosine
Voet, Voet & Pratt 2008 Fig 21.34

53 Biosynthesis of Histidine
Voet, Voet & Pratt 2008 Fig 21.36

54 Heme Biosynthesis Voet, Voet & Pratt 2008 Fig 21.38

55 Summary: Glucogenic & Ketogenic Amino Acids
Lehninger 2000 Figure 18.29

56 Amino Acid Biosynthesis: Overview I
Lehninger 2000 Figure 22.9a

57 Amino Acid Biosynthesis: Overview II
Lehninger 2000 Figure 22.9b

58 Amino Acid Biosynthesis: Overview III
Lehninger 2000 Figure 22.9c

59 End of Supplementary Material

Download ppt "Amino Acid Metabolism Student Edition 6/3/13 version"

Similar presentations

Ads by Google