Lehninger Principles of Biochemistry 5/e

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1 David L. Nelson and Michael M. Cox LEHNINGER PRINCIPLES OF BIOCHEMISTRY Fifth Edition CHAPTER 18 Amino Acid Oxidation and the Production of Urea 2008 W. H. Freeman and Company

2/3) ALL BODY TISSUES Excess amino acids AMINO ACID POOL Synthesis Biosynthesis of tissue protein Oxidative

2 Dietary proteins Synthesis (nonessential amino acids) Breakdown of tissue proteins GUT Degradation (approx. 1/3) Degradation (approx. 2/3) ALL BODY TISSUES Excess amino acids AMINO ACID POOL Synthesis Biosynthesis of tissue protein Oxidative degradation: transamination Biosynthesis of small biomolecules (purines, pyrimidines, biogenic amines, bile acids, etc.) LIVER Urea Acetyl CoA TCA intermediates Ketone bodies Fats Glucose KIDNEY LUNGS Renal excretion CO 2

* 아미노산의산화와요소의생성 동물에서의 amino acid(a.a) 산화조건 1 단백질이분해되어생성된 a.a이새로운 protein합성에필요치않을때 2 a.a 과잉일때 ( a.a은저장 ) 3 당질을이용할수없는경우 ( 기아 or 당뇨병 ) or 적절히이용할수없을때 a.a 이화경로의개요 a.

4 * 아미노산의산화와요소의생성 동물에서의 amino acid(a.a) 산화조건 1 단백질이분해되어생성된 a.a이새로운 protein합성에필요치않을때 2 a.a 과잉일때 ( a.a은저장 ) 3 당질을이용할수없는경우 ( 기아 or 당뇨병 ) or 적절히이용할수없을때 a.a 이화경로의개요 a.a, nucleotide, amine 생합성 세포내 protein 식이 protein a.a NH 4 + Glu α-ketoglutarate 탄소골격 Carbamoyl phosphate α-keto acid Urea cycle Urea 95% urine 5% feces TCA cycle 의 Aspartate-Arginosuccinate shunt TCA cycle CO 2 + H 2 O + ATP Urea cycle 의목적 : N 의독성제거 Amino group catabolism Protein 의소화 oxaloacetate glucose

5 < Overview of amino acid catabolism in mammals >

6 < Amino group catabolism >

7 < Amino group catabolism >

8 Secretin 분비 중화 < Part of the human digestive(gastrointestinal) tract >

9 대사에서의 a.a기 1. Transamination 1) a.a 전달반응 α-ketoglutarate + L-a.a PLP L-glutamate + α-keto acid transaminase L-a.a 의 NH 3+ 기를 α-ketoglutarate 에전달하여 L-Glutamate 생성 donor acceptor 2) PLP(pyridoxal phosphate) : prosthetic group으로 pyridoxin or vitamin B 6 의 coenzyme type 1 a.a전달효소의활성자리에서 a.a기의 intermediate의운반체 Carboanion 2 α-carbon 에서의반응 : Racemization, Decarboxylation, Transamination α-carbon의분해 α-carbon에 자유전자쌍 존재 매우불안정 PLP가안정화시킴

10 Transamination -NH 3 전달 < Enzyme-catalyzed transaminations >

11 < Pyridoxal phosphate, the prosthetic group of aminotransferases >

12 < Pyridoxal phosphate, the prosthetic group of aminotransferases >

13 Transamination Racemization Decarboxylation < Some amino acid transformations at the α carbon that are facilitated by pyridoxal phosphate >

14 < Reaction catalyzed by glutamate dehydrogenase >

15 < Ammonia transport in the form of glutamine >

16 ( ALT = GPT ) Cori cycle 과협조 < Glucose-alanine cycle >

17 1. 조직장해측정법 : 혈중중에있는각종효소활성을측정 1 간장질환진단 : ALT(GPT), AST(GOT) 손상된간세포로부터혈류중에새어나오므로혈청중농도를측정 GPT, GOT검사 2 Creatine kinase(ck): 심장상해시최초로혈중에나타나는심장효소 3 Lactate dehydrogenase(ldh): 손상 or 산소결핍된심근으로부터나온다.

18 2. 대사에있어서 amino acid 의역할 1) Glutamate : 간에서암모니아를유리한다. Glutamate NADP NADPH+H + L-glutamate dehydrogenase α-ketoglutarate + NH Glutamate dehydrogenase (GD) : isozyme 으로서 ADP 는 positive modulator, GTP 는 negative modulator 임. 2) Glutamine : 혈중에서 NH 4+ 를간 or 신장으로운반한다. (NH 4+ 의무독성운반형 ) 3) Alanine : NH 4+ 를근육에서간으로운반한다.

19 3. Glucose-Alanine Cycle 근육단백질 a.a NH 4 + NH 4+ 의유독성 1 혼수상태, 뇌장해유발 2 신경전달물질의고갈에영향받음 Glucose 해당 Pyruvate Alanine Glutamate alanine aminotransferase α-ketogluatarate 혈당 혈중 Alanine Glucose 신생합성 Glucose Alanine Pyruvate α-ketogluatarate alanine aminotransferase Glutamate Urea cycle NH + urea 4

20 4. 질소배설과 Urea cycle 1) NH 4 + 배설에따른생물의구분 1 Ammonotelic (NH + 4 배설성 ): NH + 4 amino nitrogen ex) 수중생물 2 Ureotelic ( 요소배설성 ): amino nitrogen urea ex) 육상동물 3 Uricotelic ( 요산배설성 ): uric acid로배설 ex) 조류, 파충류 2) Urea cycle 과 amino 기의도입경로 3) Urea cycle 과 TCA cycle 의연결 4) Carbamoyl phosphate synthetaseⅠ N-acetylglutamate synthase에의해 acetyl-coa와 glutamate로부터합성되는 N-acetylglutamate에의해 allosteric enzyme 조절을받아활성화된다 2NH HCO ATP 4- + H 2 O urea + 2ADP P 2- i + AMP H +

21 Orn transcarbamoylase Arg-Succinate synthetase Arginase Arginosuccinate lyase < Urea cycle and reactions that feed amino groups into the cycle >

22 (AST=GOT) Orn transcarbamoylase < Urea cycle and reactions that feed amino groups into the cycle >

23 < Urea cycle and reactions that feed amino groups into the cycle > Arg-Succinate synthetase Arginase Arginosuccinate lyase

24 < Links between the urea cycle and citric acid cycle >

25 고단백섭취시, 단식시증가 < Synthesis of N-acetylglutamate and its activation of carbamoyl phosphate synthetase I >

26 < N-acetyl-Glu synthase 결핍시치료제 >

27 < Nonessential and Essential Amino Acids for Humans and the Albino Rat >

28 < Treatment for deficiencies in urea cycle enzymes >

29 Ketogenic *Gluco/Ketogenic : Phe, Trp, Tyr, Ile, Thr < Summary of amino acid catabolism >

30 Vit B 12 < Some enzyme cofactors important in one-carbon transfer reactions >

7. Cobalamin (Vitamin B12) obalamin Vitamin 12) A source of adenosylcobalamine,

This enzyme is involved in the exchange of the group Co-S-CoA at C-2 of

31 7. Cobalamin (Vitamin B12) obalamin Vitamin 12) A source of adenosylcobalamine, which is a cofactor of methylmalonyl-coa mutase. This enzyme is involved in the exchange of the group Co-S-CoA at C-2 of propionate with hydrogen atom at C-3, producing succinyl-coa from L-methylmalonyl-CoA. Regulation of odd-number fatty acid and maturation factor of erythrocytes Pernicious anemia ( 악성빈혈 ) and secretion of methylmalonic acid in urea Metabolism of odd-chain fatty acid Methionine synthesis

32 < Conversions of one-carbon units on tetrahydrofolate >

33 < Synthesis of methionine and S-adenosylmethionine in an activated-methyl cycle >

34 Catabolic pathways for alanine, glycine, serine, cysteine, tryptophan, and threonine

35 Interplay of the pyridoxal phosphate and tetrahydrofolate cofactors in serine and glycine metabolism

36 Catabolic pathways for tryptophan, lysine, phenylalanine, tyrosine, leucine, and isoleucine

37 Tryptophan as precursor

38 Catabolic pathways for phenylalanine and tyrosine

39 Role of tetrahydrobiopterin in the phenylalanine hydroxylase reaction

41 Alternative pathways for catabolism of phenylalanine in phenylketonuria

42 Catabolic pathways for arginine, histidine, glutamate, glutamine, and proline

43 Catabolic pathways for methionine, isoleucine, threonine, and valine

44 Catabolic pathways for the three branchedchain amino acids: valine, isoleucine, and leucine

45 Catabolic pathway for asparagine and aspartate

Lehninger Principles of Biochemistry 5/e

David L. Nelson and Michael M. Cox LEHNINGER PRINCIPLES OF BIOCHEMISTRY Fifth Edition CHAPTER 22 Biosynthesis of Amino Acids, Nucleotides, and Related Molecules 2008 W. H. Freeman and Company Amino acid