Catabolism of Carbon skeletons of Amino acids
Amino acid metabolism Carbon skeleton • Carbon Skeleton – a carbon skeleton is the internal structure of organic molecules.
• Carbon Arrangements – The arrangement of carbon atoms in the skeleton varies from a straight line of atoms to branching formations to circular arrangements. Other atoms such as hydrogen or oxygen can bind to the carbon atoms to create molecules.
• Amino Acids – When amino acids are removed during the metabolic cycle, the original carbon skeleton remains. The carbon skeleton, stripped of the amino acids, then is free to enter another metabolic cycle to pick up new atoms.
Carbon skeleton
• A carbon skeleton refers to the pattern, in which the carbon atoms are bonded together in a molecule, without regard to differences between single and double bonds and atoms of other elements. The majority of chemical reactions in organic bonds do not break the carbon bond.
Carbon is an element that is the main building block of all living things, including plants, invertebrates and vertebrates. A carbon skeleton is a linkage or chain of carbon atoms....
significance
• Energy Production – If the cells require additional energy during the metabolic cycles, the carbon skeleton can be utilized. Oxygen is bound to the carbon atoms, in a process called oxidation, to form a water molecule, H2O, and carbon dioxide, CO2.
Catabolism – Catabolism is the process in which molecules are broken down into constituent parts, whether to create hormones, enzymes or energy. In catabolism, the remaining product is the carbon skeleton.
– Building block – Carbon is an element that is the main building block of all living things, including plants, invertebrates and vertebrates. A carbon skeleton is a linkage or chain of carbon atoms....
Break down products
Page 996 7. 6. 5. 4, 3. 2. 1.
Threoninedehydrogenase transferase hydroxymethylSerine Glycine cleavage system Serine dehydratase aminotransferaseAlanine - amino - -
ketobutyrate lyase.
-
Serine dehydratase
• PLP-enzyme forms a PLP-amino acid Schiff base (like transamination) catalyzes removal of the amino-acid’s hydrogen. • Substrate loses the -OH group undergoing an elimination of H2O rather than deamination.
• Aminoacrylate, the product of this dehydration reaction, tautomerizes to the imine which hydrolyzes to pyruvate and ammonia.
Figure 26-13 The serine dehydratase reaction.
Page 997 Page
1. Formation of Ser-PLP Schiff base, 2. Removal of the -H atom of serine, 3. elimination of OH-, 4. Hydrolysis of Schiff base, 5. Nonenzymatic tautomerization to the imine, 6. Nonenzymatic hydrolysis to form pyruvate and ammonia. Page 996 7. 6. 4, 5. 3. 2. 1.
Threoninedehydrogenase transferase Serine hydroxymethyl Glycine cleavage system dehydrataseSerine aminotransferaseAlanine - amino - -
ketobutyrate lyase.
-
Glycine conversion to pyruvate
• Gly is converted to Ser before it is transformed to pyruvate. • Gly to serine is catalyzed by serine hydroxymethyltransferase (another PLP) enzyme that also uses N5, N10-methylene- tetrahydrofolate (N5, N10-methylene-THF) cofactor to proved the C1 unit necessary for this conversion.
• The methylene group is derived from another Gly and the remaining parts are released as CO2 and ammonia catalyzed by the glycine cleavage system
Page 997 glycinecleavage system, a reactionscatalyzed the by Figure 26 multienzymecomplex. 4. 3. 2. 1. protein) dehydrogense (L dihydrolipoyl FAD NAD+ enzyme (T THF requiring (H containing protein Lipoamide protein) decarboxylase (P glycine PLP - - 14 protein) - - dependent requiring
- dependent,
- - protein)
The The
- -
Serine hydroxymethyltransferase catalyzes PLP- dependent C-C cleavage
• Catalyzes the conversion of H Thr to Gly and acetaldehyde B: • Cleaves C-C bond by O H delocalizing electrons of the H C-HC --C -COO- resulting carbanion into the 3 conjugated PLP ring: H N H C O- 2- O3PO +
N CH3
H Asn and Asp are degraded to OAA
• Asp can be converted to Asp by L-asparaginase:
O H O
- Asparagine C-CH2-C-C-O
H2N + NH3 H O 2 L-asparaginase + NH4
O H O Aspartate - C-CH2-C-C-O -O + NH3 Asn and Asp are degraded to OAA
• Asp can be converted to Asp by L-asparaginase:
O H O
- Asparagine C-CH2-C-C-O
H2N + NH3 H O 2 L-asparaginase + NH4
O H O Aspartate - C-CH2-C-C-O -O + NH3 Asn and Asp are degraded to OAA
• Transamination of aspartate to oxaloacetate:
O H O
- Aspartate C-CH2-C-C-O -O + NH3
-ketoglutarate aminotransferse glutamate
O O Oxaloacetate - C-CH2-C-C-O -O O Arg, Glu, Gln, His, and Pro are degraded to -KG
• Arg, Gln, His, and Pro are converted to Glu which is oxidized to - ketoglutarate by glutamate dehydrogenase. • Gln to Glu is catalyzed by glutaminase • His requires several reactions to get to Glu.
Figure 26- 17Degradatio n pathways of arginine, glutamate, glutamine, histidine, and proline to -
ketoglutarate.
Page 1001 Page Page 1001 1. Glutamatedehydrogense 2. Glutaminase
Gln to Gluto
- KG
Page 1001 11. 10. 9. lyase8. Histidineammonia isnonoxidativelyHis deaminated,hydrated, His to Glu Glutamate formiminotransferase Imidazoloneproponase Urocanate hydratase form the imidazole isand cleavedring to N - formiminoglutamate
Page 1001 Arg Pro and to Glu
4. Ornithine 3. Arginase 7. 6. 5. Glutamate Spontaneous Prolineoxidase dehydrogenase
- - 5 - aminotransferase - semialdehyde
Ile, Met and Val are degraded to succinyl-CoA
• Ile, Met, and Val are degraded to propionyl-CoA • Propioyl-CoA is a product of odd-chain fatty acid degradation that is converted to succinyl-CoA via propionyl-CoA carboxylase (biotin cofactor), methylmalonyl-CoA racemase, and methylmalonyl-CoA mutase (B12 cofactor).
Figure 25-18 Conversion of propionyl-CoA to
succinyl-CoA.
Page 922 Page Met degradation
• Met reacts with ATP to form S-adenosylmethionine (SAM). • SAM’s sulfonium ion is a highly reactive methyl group so this compound is involved in methylation reactions. • Methylation reactions catalyzed by SAM yield S- adenosylhomocysteine and a methylated acceptor molecule. • S-adenosylhomocysteine is hydrolyzed to homocysteine. • Homocysteine may be methylated to regenerate Met, in a B12 requiring reaction with N5-methyl-THF as the methyl donor. • Homocysteine can also combine with Ser to form cystathionine in a PLP catalyzed reaction and -ketobutyrate. • -ketobutyrate is oxidized and CO2 is released to yield propionyl- CoA. • Propionyl-CoA proceeds thorugh to succinyl-CoA.
9. 8. 7. 6. 5. 4. 3. 2. 1. 12. 11. 10.
Page 1002 (PLP) Cystathionine (PLP) Cystathionine (B12) Methionine Adenosylhomocysteinase Methyltransferase adenosyltransferase Methionine andFAD) reductase tetrahydrofolate N e hydroxymethyltransferas or serine Glycine mutase Methylmalonyl racemase Methylmalonyl carboxylase Propionyl dehydrogenase
- 5 ketoacid ,N 10
- methylene
cleavagesystem
-
CoA (coenzyme B12
synthase (biotin)
- - -
- CoA CoA synthase synthase -
Page 987 Figure 25-18 Conversion of propionyl-CoA to
succinyl-CoA.
Page 922 Page Ile, Met and Val are degraded to succinyl-CoA
• Ile, Met, and Val are degraded to propionyl-CoA • Propioyl-CoA is a product of odd-chain fatty acid degradation that is converted to succinyl-CoA via propionyl-CoA carboxylase (biotin cofactor), methylmalonyl-CoA racemase, and methylmalonyl-CoA mutase (B12 cofactor).
Branched chain amino acid degradation
• Degradation of Ile, Leu, and Val use common enzymes for the first three steps 1. Transamination to the corresponding -keto acid 2. Oxidative decarboxylation to the corresponding acyl-CoA 3. Dehydrogenation by FAD to form a double bond.
First three enzymes 1. Branched-chain amino acid aminotransferase 2. Branched-chain keto acid dehydrogenase (BCKDH) 3. Acyl-CoA dehydrogeanse degradati 26 branched on of the of on isoleucin acids (A) leucine and (C) valine amino Figure Page 1004 - e chain - 21 , (B) , The , .
degradati branched 26 on ofthe isoleucin acids acids (A) leucine and (C) and (C) valine amino Figure Page 1004 - e chain - 21 , (B) The , .
Page 1004 6. 5. 4. Afterthree the steps,for pathwaythe Ile, continuessimilar to
Page 1004 NAD+ Enoyl mutase). methylmalonyl fattyoxidation acid (propionyl Acetyl - hydroxyacyl -
- CoA hydrataseCoA CoA acetyltransferase
- CoA dehydrogenase - CoA racemase,CoA methylmalonyl -
double bond hydration bond double - -
thiolytic cleavagethiolytic CoA carboxylase,CoA -
dehydrognationby
- CoA
Laststeps 3 similarto fatty oxidationacid 10. 9. 8. 7. For Valine:
Page 1004 oxidative carboxylation Methylmalonatesemialdehyde dehydrogenase dehydration CoA Enoyl
- hydroxy hydroxyisobutyrate dehydrogenase
- CoA hydrataseCoA - isobutyryl
- - CoA hydrolase
double bond hydrationbond double
- hydrolysis of -
second
-
Leucine Acetoacetate 13. 12. 11. For
Page 1004 Leucine HMG reaction reaction(biotin)
- - is a methylglutaconyl methylcronyl : -
ketogenic CoA
can be converted to 2acetyl
lyase -
CoA amino amino acid!
-
CoA carboxylase
hydratase
- carboxylation - hydration - CoA
Lys is also ketogenic
• Leu proceeds through a typical branched amino acid breakdown but the final products are acetyl-CoA and acetoacetate.
• Most common Lys degradative pathway in liver goes through the formation of the -ketoglutarate-lysine adduct saccharopine.
• 7 of 11 reactions are found in other pathways. • Reaction 4: PLP-dependent transamination • Reaction 5: oxidative decarboxylation of an a-keto acid by a multienzyme complex similar to pyruvate dehydragense and a-ketoglutarate dehydrogenase. • Reactions 6,8,9: fatty acyl-CoA oxidation. • Reactions 10 and 11 are standard ketone body formation reactions. Page 1007
Fate of glycine Fate of amino acid Fate of Individual Amino Acids • Seven to acetyl-CoA – Leu, Ile, Thr, Lys, Phe, Tyr, Trp • Six to pyruvate – Ala, Cys, Gly, Ser, Thr, Trp • Five to -ketoglutarate – Arg, Glu, Gln, His, Pro • Four to succinyl-CoA – Ile, Met, Thr, Val • Two to fumarate – Phe, Tyr • Two to oxaloacetate – Asp, Asn