M2aminoacidmetabolism

1、M2 amino acid metabolismessential amino acid 必需氨基酸必需氨基酸glucogenic amino acid 生生糖糖氨基酸氨基酸ketogenic amino acid 生生酮酮氨基酸氨基酸oxidative deamination 氧化氧化脱脱氨基氨基transamination 转转氨基氨基 pyridoxal phosphate 磷酸吡哆醛磷酸吡哆醛combinative transamination 联合脱氨基联合脱氨基alkaptonuria 尿黑病尿黑病phenylketonuria 苯丙苯丙酮酮尿症尿症1 Bisoynthesis o

2、f amino acids Those amino acids that are supplied in the diet and cannot be synthesized by the body are referred to as essential amino acids. In humans the essential amino acids are His (children), Ile, Leu, Lys, Met, Phe, Thr, Trp and Val. 假假 设设 来来 写写 一一 两两 本本 书书甲硫甲硫(蛋蛋) 色色 赖赖 缬缬 异亮异亮 亮亮 苯丙苯丙 苏苏假假

3、设设 来来 写写 足足 一一 两两 本本 书书甲硫甲硫(蛋蛋) 色色 赖赖 缬缬 组组 异亮异亮 亮亮 苯丙苯丙 苏苏 In nonessential amino acids, their carbon skeletons come from key intermediates in central metabolic pathways. 谷氨酸家族谷氨酸家族天冬氨酸家族天冬氨酸家族丝氨酸家族丝氨酸家族丙酮酸家族丙酮酸家族芳香氨基酸家族芳香氨基酸家族2 Amino acid degradation The -amino group is removed first and the result

4、ing carbon skeleton is converted into one or more major metabolic intermediates and used as metabolic fuel. Amino acids that are degraded to pyruvate, -ketoglutarate, succinyl CoA, fumarate and oxaloacetate are termed glucogenic amino acids as they can give rise to the net synthesis of glucose. Amin

5、o acids that are degraded to acetyl CoA or acetoacetyl CoA are termed ketogenic amino acids because they give rise to ketone bodies. Solely ketogenic amino acids: Leu and Lys. Both ketogenic and glucogenic amino acids: Phe, Trp Tyr, and Ile（芳香异亮芳香异亮）Solely glucogenic amino acids: others (14)3 Transa

6、mination（转氨基作用）（转氨基作用）During transamination process the -amino group of most amino acids is transferred to -ketoglutarate to form glutamate and the corresponding -keto acid.The enzymes that catalyze these reactions are called transaminases (amino-transferases). transaminasealanine transaminase (ALT)

7、 aspartate transaminase (AST) Q1:Why transaminase can be used in the diagnostics?Pyridoxal phosphatepyridoxamine phosphate 4 Oxidative deamination of glutamate Glutamate - ketoglutarateGlutamate dehydrogenaseAllosteric inhibitors: GTP and ATPAllosteric activators: GDP and ADP Liver, kidney The forms

8、 of deamination （脱氨基的主要方式）（脱氨基的主要方式）(1)Oxidative deamination (氧化脱氨基）氧化脱氨基）(2)Transamination（转氨基）（转氨基）(3) Combinative transamination (联合脱氨基联合脱氨基)R-CH-COOHNH2R-C-COOHOCOOHCH2COOHCO2COOHCH2COOHCHNH22NAD+ + H2ONADH + H+ + NH3-ketoglutarate-amino acid-keto acidL-glutamate dehydrogenasetransaminaseGlu5 Am

9、ino acid oxidases L-amino acid oxidase utilizes flavin mononucleotide (FMN) as its coenzyme, with the resulting FMNH2 being reoxidized by molecular O2, a process that also generates the toxic H2O2. 6 Metabolism of phenylalaninePhenylalanine 苯丙氨酸苯丙氨酸Phenylalanine hydroxylase 苯丙氨酸羟化酶苯丙氨酸羟化酶Tyrosine 酪氨

10、酸酪氨酸p-hydroxyphenylpyruvate 对对-羟苯丙酮酸羟苯丙酮酸Transaminase 转氨酶转氨酶p-hydroxyphenylpyruvate hydroxylase 对对-羟苯丙酮酸羟化酶羟苯丙酮酸羟化酶Homogentisate 尿黑酸尿黑酸Homogentisate oxidase 尿黑酸氧化酶尿黑酸氧化酶Fumarate, acetoacetate 延胡索酸、乙酰乙酸延胡索酸、乙酰乙酸7 Inborn errors of metabolism （先天性代谢异常）（先天性代谢异常） Two inborn errors of metabolism are known

11、 that affect phenylalanine metabolism. These are inherited metabolic disorders caused by the absence of one of the enzymes in the pathway. (1)Alkaptonuria (尿黑病尿黑病）is caused by the absence of homogentisate oxidase （尿黑酸氧化尿黑酸氧化酶）酶）. (2)In phenylketonuria (苯丙酮尿症），苯丙酮尿症），there is a block in the hydroxylation of phenylalanine to tyrosine caused by an absence or deficiency of phenylalanine hydroxylase or, more rarely, of its tetrahydrobiopterin （四氢生物蝶呤）（四氢生物蝶呤）coenzyme. Q2