1. Amino Acid Oxidation and Production of Urea
Chapter 18
Amino Acid Oxidation and Production of Urea

2. Overview
18.1 Metabolic Fates of Amino Groups: 음식물로 섭취한 단백질의 소화, 아미노산 분해의 첫 단계인 탈아미노 반응과 생성된 암모니아를 처리하기 위한 간으로의 운반
18.2 Nitrogen Excretion and the Urea Cycle: 암모니아를 요소로 변환하는 과정인 urea cycle의 단계별 반응과 조절 메커니즘
18.3 Pathways of Amino Acid Degradation: 아미노산의 탈아미노 결과 생긴 탄소 골격의 대사 과정과 자주 등장하는 반응의 유형 및 조효소

3. 17장
14장
18장
16장
19장

4. ▪ 에너지원으로서의 아미노산
▫ 육식동물: 식후에는 90 %의 에너지 생산
▫ 초식동물: 아주 적은 양만 에너지원으로 사용
▫ 미생물: 환경에 따라 주위의 아미노산 흡수, 대사
▫ 식물: 에너지원으로 거의 사용하지 않음. 다만, 생합성의 전구체 획득을 위해 아미노산 분해
▪ 동물에 있어서 아미노산 산화가 일어날 경우
▫ Protein turnover에서 재활용되지 않는 과잉의 아미노산
▫ 음식물로 섭취한 양이 필요량을 초과할 때 (아미노산은 저장하지 않음)
▫ 단식(탄수화물 부족)이나 당뇨(탄수화물의 이용이 저조)일 때 에너지원으로 사용

5. Oxidative deamination (18-1)
Transamination
Oxidative deamination
(18-1)
Urea cycle
(18-2)
FIGURE 18-1 Overview of amino acid catabolism in mammals. The amino groups and the carbon skeleton take separate but interconnected pathways
FIGURE 18-1 Overview of amino acid catabolism in mammals.

6. 18.1 Metabolic Fates of Amino Groups

7. FIGURE 18-2 Amino group catabolism.
transamination
FIGURE 18-2 Amino group catabolism. (a) Overview of catabolism of amino groups (shaded) in vertebrate liver.
FIGURE 18-2 Amino group catabolism.

8. Dietary Protein Is Enzymatically Degraded to Amino Acids
HCl (pH )
pepsinogen
HCl (unfold→auto-catalysis)
pepsin
FIGURE 18-3 Part of the human digestive (gastrointestinal) tract. (a) The parietal cells and chief cells of the gastric glands secrete their products in response to the hormone gastrin. Pepsin begins the process of protein degradation in the stomach. (b) The cytoplasm of exocrine cells is completely filled with rough endoplasmic reticulum, the site of synthesis of the zymogens of many digestive enzymes. The zymogens are concentrated in membrane-enclosed transport particles called zymogen granules. When an exocrine cell is stimulated, its plasma membrane fuses with the zymogen granule membrane and zymogens are released into the lumen of the collecting duct by exocytosis. The collecting ducts ultimately lead to the pancreatic duct and thence to the small intestine. (c) Amino acids are absorbed through the epithelial cell layer (intestinal mucosa) of the villi and enter the capillaries. Recall that the products of lipid hydrolysis in the small intestine enter the lymphatic system after their absorption by the intestinal mucosa (see Figure 17-1).
Phe, Trp, Tyr의 N-말단 쪽 절단
bicarbonate
FIGURE 18-3 Part of the human digestive (gastrointestinal) tract.

9. procarboxypeptidase A,B trypsin: Lys, Arg의 C-말단 쪽 절단 enteropeptidase
Pancreatic enzymes
pancreatic trypsin inhibitor 때문에 췌장에서 활성화되지 않음 (2중 안전 장치)
pancreas
cholecystokinin
trypsinogen
chymotrypsinogen
procarboxypeptidase A,B
trypsin: Lys, Arg의 C-말단 쪽 절단
enteropeptidase
p-chymotrypsin
a-chymotrypsin
Phe, Trp, Tyr의 C-말단 쪽 절단
carboxypeptidases
aminopeptidases
C-말단에서 차례로 절단
N-말단에서 차례로 절단
secretin
(hormone)
bicarbonate
위산중화
Acute pancreatitis
Zymogen이 췌장에서 너무 일찍 활성화되어 췌장 조직의 단백질을 분해. 극심한 통증. 치명적일 수 있다.

10. FIGURE 18-4 Enzyme-catalyzed transaminations.
Pyridoxal Phosphate Participates in the Transfer of a-Amino Groups to a-Ketoglutarate
▪ 아미노산의 종류에 따라 여러 aminotransferase들이 존재. 두 개의 기질에 의한 ping-pong mechanism.
▪ DG~0: 가역적
transamination
FIGURE 18-4 Enzyme-catalyzed transaminations. In many aminotransferase reactions, α-ketoglutarate is the amino group acceptor. All aminotransferases have pyridoxal phosphate (PLP) as cofactor. Although the reaction is shown here in the direction of transfer of the amino group to α-ketoglutarate, it is readily reversible
Transaminase라고도 함
FIGURE 18-4 Enzyme-catalyzed transaminations.

11. Assays for Tissue Damage
BOX 18-1
간에서 transamination이 활발히 진행되므로 aminotransferase의 농도가 높다.
간이 손상되면 간세포의 파열에 의해 이들 transaminase가 혈액 속으로 누출
혈액 속 transaminase 활성은 간손상에 비례
GOT: glutamate-oxaloacetate transaminase = aspartate aminotransferase
GPT: glutamate-pyruvate transaminase = alanine aminotransferase

12. Pyridoxal phosphate (PLP)
FIGURE 18-5b Pyridoxal phosphate, the prosthetic group of aminotransferases. (b) Pyridoxal phosphate is bound to the enzyme through noncovalent interactions and a Schiff-base (aldimine) linkage to a Lys residue at the active site. The steps in the formation of a Schiff base from a primary amine and a carbonyl group are detailed in Figure 14-5.
FIGURE 18-5 Pyridoxal phosphate, the prosthetic group of aminotransferases.
Cont’d

13. PLP
FIGURE 18-5c Pyridoxal phosphate, the prosthetic group of aminotransferases. (c) PLP (red) bound to one of the two active sites of the dimeric enzyme aspartate aminotransferase, a typical aminotransferase
Cont’d

14. PLP PLP Schiff base Lys258 (aldimine linkage) Lys258 Schiff base
FIGURE 18-5d Pyridoxal phosphate, the prosthetic group of aminotransferases. (d) close-up view of the active site, with PLP (red, with yellow phosphorus) in aldimine linkage with the side chain of Lys258 (purple)
2-methylaspartate
(a substrate analog)

15. transamination
racemization
decarboxylation
MECHANISM FIGURE 18-6 Some amino acid transformations at the α carbon that are facilitated by pyridoxal phosphate. Pyridoxal phosphate is generally bonded to the enzyme through a Schiff base, also called an internal aldimine. This activated form of PLP readily undergoes transimination to form a new Schiff base (external aldimine) with the α-amino group of the substrate amino acid (see Figure 18-5b, d). Three alternative fates for the external aldimine are shown: A transamination, B racemization, and C decarboxylation. The PLP–amino acid Schiff base is in conjugation with the pyridine ring, an electron sink that permits delocalization of an electron pair to avoid formation of an unstable carbanion on the α carbon (inset). A quinonoid intermediate is involved in all three types of reactions. The transamination route A is especially important in the pathways described in this chapter. The pathway highlighted here (shown left to right) represents only part of the overall reaction catalyzed by aminotransferases. To complete the process, a second α-keto acid replaces the one that is released, and this is converted to an amino acid in a reversal of the reaction steps (right to left). Pyridoxal phosphate is also involved in certain reactions at the β and γ carbons of some amino acids (not shown)
FIGURE 18-6 Some amino acid transformations at the a carbon that are facilitated by pyridoxal phosphate.

16. Glutamate Releases Its Amino Group As Ammonia in the Liver
Transamination
a-Ketoglutarate
Amino acid
a-Keto acid
Oxidative deamination
“Transdeamination”
Transamination과 oxidative deamination을 통해 아미노산의 –NH2가 NH3로 배출
FIGURE 18-7 Reaction catalyzed by glutamate dehydrogenase. The glutamate dehydrogenase of mammalian liver has the unusual capacity to use either NAD+ or NADP+ as cofactor. The glutamate dehydrogenases of plants and microorganisms are generally specific for one or the other. The mammalian enzyme is allosterically regulated by GTP and ADP.
FIGURE 18-7 Reaction catalyzed by glutamate dehydrogenase.

17. Amino acid
transdeamination
blood
liver
FIGURE 18-8 Ammonia transport in the form of glutamine from muscle and other tissues.

18. Alanine Transports Ammonia from Skeletal Muscles to the Liver
FIGURE 18-9 Glucose-alanine cycle. Alanine serves as a carrier of ammonia and of the carbon skeleton of pyruvate from skeletal muscle to liver. The ammonia is excreted and the pyruvate is used to produce glucose, which is returned to the muscle.
FIGURE 18-9 Glucose-alanine cycle.

19. glutamine synthetatse
Summary
amino acids
a-keto acids
“glucose-alanine cycle”
NH4+
a-ketoglutarate
glutamate
glutamine
glutamine synthetatse
MUSCLE and OTHER TISSUES
alanine
pyruvate
glucose
blood
LIVER
alanine
pyruvate
glucose
glutamine
glutaminase
NH4+
a-ketoglutarate
glutamate
glutamate
glutamate
dehydrogenase
urea (liver)
ammonium salt
(in kidneys under acidosis)
NH4+

20. 18.2 Nitrogen Excretion and the Urea Cycle

21. 물은 너무 무겁다
물이 귀한 건조한 곳에 서식
birds, reptiles
uric acid
plants: 100 % recycle
purine
urea cycle
NH3
urea
bacteria, protozoa, bony fish
most terrestrial animals
주위의 물로 쉽게 희석

22. Urea Is Produced from Ammonia in Five Enzymatic Steps
HCO3-, ATP
NH4+
Carbamoyl phosphate
Carbamoyl phosphate synthetase I
Ornithine transcarbamoylase
Ornithine
H2NCNH2 = O
Urea
Citrulline
Aspartate,
ATP
Argininosuccinate synthetase
Arginase
FIGURE Urea cycle and reactions that feed amino groups into the cycle. The enzymes catalyzing these reactions (named in the text) are distributed between the mitochondrial matrix and the cytosol. One amino group enters the urea cycle as carbamoyl phosphate, formed in the matrix; the other enters as aspartate, formed in the matrix by transamination of oxaloacetate and glutamate, catalyzed by aspartate aminotransferase. The urea cycle consists of four steps. 1 Formation of citrulline from ornithine and carbamoyl phosphate (entry of the first amino group); the citrulline passes into the cytosol. 2 Formation of argininosuccinate through a citrullyl-AMP intermediate (entry of the second amino group). 3 Formation of arginine from argininosuccinate; this reaction releases fumarate, which enters the citric acid cycle. 4 Formation of urea; this reaction also regenerates ornithine. The pathways by which NH4+ arrives in the mitochondrial matrix of hepatocytes were discussed in Section 18.1.
Arginine
Argininosuccinate
Argininosuccinase

23. FIGURE (part 1) Urea cycle and reactions that feed amino groups into the cycle. The enzymes catalyzing these reactions (named in the text) are distributed between the mitochondrial matrix and the cytosol. One amino group enters the urea cycle as carbamoyl phosphate, formed in the matrix; the other enters as aspartate, formed in the matrix by transamination of oxaloacetate and glutamate, catalyzed by aspartate aminotransferase. The urea cycle consists of four steps. 1 Formation of citrulline from ornithine and carbamoyl phosphate (entry of the first amino group); the citrulline passes into the cytosol. 2 Formation of argininosuccinate through a citrullyl-AMP intermediate (entry of the second amino group). 3 Formation of arginine from argininosuccinate; this reaction releases fumarate, which enters the citric acid cycle. 4 Formation of urea; this reaction also regenerates ornithine. The pathways by which NH4+ arrives in the mitochondrial matrix of hepatocytes were discussed in Section 18.1.
Cont’d
FIGURE Urea cycle and reactions that feed amino groups into the cycle.

24. FIGURE (part 2) Urea cycle and reactions that feed amino groups into the cycle. The enzymes catalyzing these reactions (named in the text) are distributed between the mitochondrial matrix and the cytosol. One amino group enters the urea cycle as carbamoyl phosphate, formed in the matrix; the other enters as aspartate, formed in the matrix by transamination of oxaloacetate and glutamate, catalyzed by aspartate aminotransferase. The urea cycle consists of four steps. 1 Formation of citrulline from ornithine and carbamoyl phosphate (entry of the first amino group); the citrulline passes into the cytosol. 2 Formation of argininosuccinate through a citrullyl-AMP intermediate (entry of the second amino group). 3 Formation of arginine from argininosuccinate; this reaction releases fumarate, which enters the citric acid cycle. 4 Formation of urea; this reaction also regenerates ornithine. The pathways by which NH4+ arrives in the mitochondrial matrix of hepatocytes were discussed in Section 18.1.

25. FIGURE 18-11 Nitrogen-acquiring reactions in the synthesis of urea
MECHANISM FIGURE 18-11a Nitrogen-acquiring reactions in the synthesis of urea. The urea nitrogens are acquired in two reactions, each requiring ATP. (a) In the reaction catalyzed by carbamoyl phosphate synthetase I, the first nitrogen enters from ammonia. The terminal phosphate groups of two molecules of ATP are used to form one molecule of carbamoyl phosphate. In other words, this reaction has two activation steps (1 and 3).
FIGURE Nitrogen-acquiring reactions in the synthesis of urea

26. The Citric Acid and Urea Cycles Can Be Linked26
FIGURE Links between the urea cycle and citric acid cycle.

27. The Activity of the Urea Cycle Is Regulated at Two Levels
Level 1 (long term): 육식 또는 단식처럼 단백질을 에너지원으로 사용해야 할 때 NH3의 처리를 위해 urea cycle의 4 효소와 carbamoyl phosphate synthetase I의 단백질 합성이 증가
Level 2 (short term): Allosteric regulaton of carbamoyl phosphate synthetase I → 오른쪽 그림
FIGURE Synthesis of N-acetylglutamate and its activation of carbamoyl phosphate synthetase I.
FIGURE Synthesis of N-acetylglutamate and its activation of carbamoyl phosphate synthetase I.
N-acetylglutamate는 arginine 생합성의 중간체이지만 간에서는 특이하게도 arginine합성에 필요한 다른 효소가 없어서 urea cycle 조절에만 사용된다.

28. Pathway Interconnections Reduce the Energetic Cost of Urea Synthesis
AMP
(2)
ATP
2.5ATP
(-2.5)
2ADP
2ATP
(2)
NH4+
Urea 1 몰당 4몰 ATP 소비하고 2.5몰 회수 → net 1.5 몰의 ATP 필요

29. Genetic Defects in the Urea Cycle Can Be Life-Threatening
TABLE 18-1 Nonessential and Essential Amino Acids for Humans and the Albino Rat
필수아미노산 때문에 단백질 섭취가 불가피 → Urea cycle이 필수적

30. FIGURE 18-14 Treatment for deficiencies in urea cycle enzymes.
Fatty acyl-CoA와 같은 유형
ATP
AMP+PPi
b-oxidation
ATP
AMP+PPi
▪ glycine과 glutamine이 제거되어 이 아미노산들을 합성하는데 NH3가 사용되므로 urea cycle에 문제가 있어도 NH3가 축적되지 않음.
FIGURE Treatment for deficiencies in urea cycle enzymes. The aromatic acids benzoate and phenylbutyrate, administered in the diet, are metabolized and combine with glycine and glutamine, respectively. The products are excreted in the urine. Subsequent synthesis of glycine and glutamine to replenish the pool of these intermediates removes ammonia from the bloodstream.
FIGURE Treatment for deficiencies in urea cycle enzymes.
Cont’d

31. Treatment for Deficiencies in Urea Cycle Enzymes (Fig. 18-14)
Fatty acyl-CoA와 같은 유형
Gly과 Gln을 배출

32. ▪ N-acetylglutamate synthase에 이상이 있을 경우 carbamoyl phosphate synthetase I의 activator인 N-acetylglutamate 유사체 사용
유사체
FIGURE 18-13

33. 18.3 Pathways of Amino Acid Degradation
▪ 복잡한 반응에서 무엇을 공부할 것인가?
자주 등장하는 반응의 유형 및 메커니즘이나 의학적 측면에 중점을 두고 공부

34. FIGURE 18-15 Summary of amino acid catabolism.
FIGURE Summary of amino acid catabolism. Amino acids are grouped according to their major degradative end product. Some amino acids are listed more than once because different parts of their carbon skeletons are degraded to different end products. The figure shows the most important catabolic pathways in vertebrates, but there are minor variations among vertebrate species. Threonine, for instance, is degraded via at least two different pathways (see Figure 18-19, 18-27), and the importance of a given pathway can vary with the organism and its metabolic conditions. The glucogenic and ketogenic amino acids are also delineated in the figure, by color shading. Notice that five of the amino acids are both glucogenic and ketogenic. The amino acids degraded to pyruvate are also potentially ketogenic. Only two amino acids, leucine and lysine, are exclusively ketogenic.
FIGURE Summary of amino acid catabolism.

35. Several Enzyme Cofactors Play Important Roles in Amino Acid Catabolism
Reaction type
Reaction
cofactor
Transamination
Amino acid1 + a-keto acid2 → Amino acid2 + a-keto acid1
Pyridoxal phosphate
One-carbon transfer
CO2 (most oxidized) transfer
Biotin
-CHO, -CH2OH, -CH3 transfer
Tetrahydrofolate
-CH3 (most reduced) transfer
S-Adenosylmethionine
(THF와 연계)
Monoxygenation
RCH3 → RCH2OH
Tetrahydrobiopterin
FIGURE Some enzyme cofactors important in one-carbon transfer reactions. The nitrogen atoms to which one-carbon groups are attached in tetrahydrofolate are shown in blue.

36. (1) One Carbon Carrier: Biotin= C
HCO3 - - O
ATP ADP + Pi
FIGURE (part 1) Some enzyme cofactors important in one-carbon transfer reactions. The nitrogen atoms to which one-carbon groups are attached in tetrahydrofolate are shown in blue.
▪ 가장 높은 산화상태인 CO2를 운반
▪ CH3C(O)COO- + HCO3- → -OOC-CH2-C(O)-COO- (pyruvate carboxylase: citric acid cycle에 oxaloacetate를 보충)
▪ CH3C(O)SCoA + HCO3- → -OOC-CH2-C(O)SCoA (acetyl-CoA carboxylase: 지방산 합성의 출발물질인 malonyl-CoA 합성)

37. (2) One Carbon Carrier: Tetrahydrofolate
▪ 1C donor는 대부분의 경우 serine(곁사슬)이며 formate일 수도 있다.
▪ 1C은 N-5, N-10 또는 양쪽(-CH2-)에 걸쳐 결합한다.
▪ 산화상태를 판단하기 위한 전자수 계산
FIGURE (part 2) Some enzyme cofactors important in one-carbon transfer reactions. The nitrogen atoms to which one-carbon groups are attached in tetrahydrofolate are shown in blue.

38. -CH3 (6e-) -CH2OH, -CH2- (4e-) -CHO, -CH=NH (2e-) N5 N5 N5 H C H H C H•• •• ••
H C H •• ••
H C H •• ••
H C •• •• •• •• •• H OH O
methyl
hydroxymethyl
formyl N5 N5 •• ••
H C N10 •• ••
H C •• •• •• H •• NH
methylene
formimino

39. FIGURE 18-17 Conversions of one-carbon units on tetrahydrofolate.
good –CHO donor
His
poor –CHO donor
(stable)
FIGURE Conversions of one-carbon units on tetrahydrofolate.

40. (3) One Carbon Carrier: S-Adenosylmethionine
FIGURE (part 3) Some enzyme cofactors important in one-carbon transfer reactions. The nitrogen atoms to which one-carbon groups are attached in tetrahydrofolate are shown in blue.
▪ 가장 환원된 상태인 CH3-를 운반
▪ methyl-THF 보다 훨씬 강력한 methyl group donor이다.

41. ATP의 5’-C을 공격하여 PPPi를 방출하는 반응은 2가지 뿐. 나머지 하나는 coenzyme B12를 형성하는 반응.
methylmalonyl-CoA mutase와 함께 포유동물 내에서 coenzyme B12를 사용하는 유일한 효소이다.
FIGURE Synthesis of methionine and S-adenosylmethionine in an activated methyl cycle.

42. FIGURE 18-19 Catabolic pathways for Ala, Gly, Ser, Cys, Trp, and Thr.
Six Amino Acids (Gly, Ala, Ser, Cys, Thr, Trp) Are Degraded to Pyruvate
dehydrogenation
3rd pathway for Gly degradation
mammals
1-C (methylene) transfer
bacteria
nonketonic hyperglycemia
(정신박약, 유아 사망)
transamination
FIGURE Catabolic pathways for Ala, Gly, Ser, Cys, Trp, and Thr.

43. Schiff base b
Ser a
imine
(keto)
dehydration
enamine
(enol)
MECHANISM FIGURE Interplay of the pyridoxal phosphate and tetrahydrofolate cofactors in serine and glycine metabolism. The first step in each of these reactions (not shown) involves the formation of a covalent imine linkage between enzyme-bound PLP and the substrate amino acid—serine in (a), glycine in (b) and (c). (a) A PLP-catalyzed elimination of water in the serine dehydratase reaction (step 1) begins the pathway to pyruvate. (b) In the serine hydroxymethyltransferase reaction, a PLP-stabilized carbanion (product of step 1) is a key intermediate in the reversible transfer of the methylene group (as —CH2—OH) from N5,N10-methylenetetrahydrofolate to form serine. (c) The glycine cleavage enzyme is a multienzyme complex, with components P, H, T, and L. The overall reaction, which is reversible, converts glycine to CO2 and NH4+, with the second glycine carbon taken up by tetrahydrofolate to form N5,N10-methylenetetrahydrofolate. Pyridoxal phosphate activates the α carbon of amino acids at critical stages in all these reactions, and tetrahydrofolate carries one-carbon units in two of them (see Figure 18-6, 18-17).
FIGURE Interplay of the pyridoxal phosphate and tetrahydrofolate cofactors in serine and glycine metabolism.
Cont’d

44. Gly
Schiff base
-CH2- = -CH2OH
Cont’d

45. Schiff base
Gly
lipoic acid

46. FIGURE 18-21 Catabolic pathways for Trp, Lys, Phe, Tyr, and Ile.
Seven Amino Acids (Trp, Lys, Phe, Tyr, Leu, Ile, and Thr) Are Degraded to Pyruvate
Monoxygenation
Oxidative decarboxylation
FIGURE Catabolic pathways for Trp, Lys, Phe, Tyr, and Ile.
citric acid cycle

47. FIGURE 18-22 Tryptophan as precursor.
FIGURE Tryptophan as precursor. The aromatic rings of tryptophan give rise to nicotinate (niacin), indoleacetate, and serotonin. Colored atoms trace the source of the ring atoms in nicotinate.
auxin
FIGURE Tryptophan as precursor.

48. FIGURE 18-23 Catabolic pathways for phenylalanine and tyrosine.
Monoxygenation
Transamination
FIGURE Catabolic pathways for phenylalanine and tyrosine. In humans these amino acids are normally converted to acetoacetyl-CoA and fumarate. Genetic defects in many of these enzymes cause inheritable human diseases (shaded yellow).
FIGURE Catabolic pathways for phenylalanine and tyrosine.

49. Phenylalanine Catabolism Is Defective in Some People
(1) Phenylketonuria (PKU): phenylalanine hydroxylase의 결함
“mixed function oxidase” (21장)
FIGURE Role of tetrahydrobiopterin in the phenylalanine hydroxylase reaction.

50. ▪ phenylacetate와 phenyllactate 축적 ▪ 심한 정신박약 ▪ 상당히 흔한 질병 → 신생아일 때 검사 필요
Phe hydroxylase
Tyrosine (정상적 경로)
▪ 처음 발견된 대사 관련 질병
▪ phenylacetate와 phenyllactate 축적
▪ 심한 정신박약
▪ 상당히 흔한 질병 → 신생아일 때 검사 필요
▪ 치료법: phenylalanine을 제한하는 식이요법. 성장하면서 완화.
Transamination
FIGURE Alternative pathways for catabolism of phenylalanine in phenylketonuria. In PKU, phenylpyruvate accumulates in the tissues, blood, and urine. The urine may also contain phenylacetate and phenyllactate.
FIGURE Alternative pathways for catabolism of phenylalanine in phenylketonuria.

51. FIGURE 18-26 Catabolic pathways for Arg, His, Glu, Gln, and Pro.
Five Amino Acids (Pro, Glu, Gln, Arg, His) Are Converted to a-Ketoglutarate
Transamination
Urea cycle
Dehydrogenation
Oxidative
deamination
FIGURE Catabolic pathways for Arg, His, Glu, Gln, and Pro.
Citric acid cycle

52. Four Amino Acids (Met, Thr, Val, Ile) Are Converted to Succinyl-CoA
FIGURE Catabolic pathways for methionine, isoleucine, threonine, and valine.
AdoMet 합성 경로
Serine hydratase(Serine → Pyruvate)와 유사
Oxidative
Decarboxylation
(TPP)
FIGURE (part 1) Catabolic pathways for methionine, isoleucine, threonine, and valine. These amino acids are converted to succinyl-CoA; isoleucine also contributes two of its carbon atoms to acetyl-CoA (see Figure 18-21). The pathway of threonine degradation shown here occurs in humans; a pathway found in other organisms is shown in Figure The route from methionine to homocysteine is described in more detail in Figure 18-18; the conversion of homocysteine to α-ketobutyrate in Figure 22-14; the conversion of propionyl-CoA to succinyl-CoA in Figure
(Biotin)

53. Branched-Chain Amino Acids Are Not Degraded in the Liver
succinyl-CoA
Oxidative decarboxylation
Transamination
succinyl-CoA
FIGURE Catabolic pathways for the three branchedchain amino acids: valine, isoleucine, and leucine. All three pathways occur in extrahepatic tissues and share the first two enzymes, as shown here. The branched-chain α-keto acid dehydrogenase complex is analogous to the pyruvate and α-ketoglutarate dehydrogenase complexes and requires the same five cofactors (some not shown here). This enzyme is defective in people with maple syrup urine disease.
acetyl-CoA
FIGURE 18-28
간이 아니고 muscle, adipose, kidney, brain에서 분해

54. Asparagine and Aspartate Are Degraded to Oxaloacetate
FIGURE Catabolic pathway for asparagine and aspartate. Both amino acids are converted to oxaloacetate.
Transamination O
FIGURE Catabolic pathway for asparagine and aspartate.

56. 감사합니다!
END