Protein Degradation and Amino Acids Metablism 蛋白质的分解代谢 Protein Degradation and Amino Acids Metablism

Contents Protein degradation Amino Acid Degradation Biosynthesis of amino acids

I. Protein Degradation

Biological Functions of Proteins Enzymes Transport proteins Nutrient and storage proteins Contractile or motile proteins Structural proteins Defense proteins Regulatory proteins Other proteins

Nitrogen balance Zero or total nitrogen balance: the intake = the excretion (adult) Positive nitrogen balance: the intake > the excretion （during pregnancy, infancy, childhood and recovery from severe illness or surgery ） Negative nitrogen balance: the intake < the excretion （following severe trauma, surgery or infections. Prolonged periods of negative balance are dangerous and fatal. ）

Classification of amino acids non-essential amino acids - can be synthesized by an organism - usually are prepared from precursors in 1-2 steps Essential amino acids *** - can not be made endogenously - must be supplied in diet

Nonessential Essential Alanine Arginine* Asparagine Histidine * Aspartate Valine Cysteine Lysine Glutamate Isoleucine Glutamine Leucine Glycine Phenylalanine Proline Methionine Serine Threonine Tyrosine Tyrptophan *The amino acids Arg, His are considered “conditionally essential” for reasons not directly related to lack of synthesis and  they are essential  for growth only

Degradation of dietary proteins

Degradation of proteins Degraded by ubiquitin(泛素) label 2. Degraded by the protease and the peptidase in the Lysosome(溶酶体）

1. Degraded by ubiquitin(泛素) label Ubiquitin, a extremely well conserved 76-residue protein, Ubiquitin binds lysine side chain Degrade abnormal protein of her own Targets for hydrolysis by proteosomes in cytosol and nucleus ATP required

2. Degraded by the protease and the peptidase in the Lysosome(溶酶体） non- ATP required the hydrolysis-selective are bad Degrade adventive protein

The ubiquitin degradation pathway E2：carrier protein E3：ligase ATP AMP+PPi E2-SH E3 E1-S- E2-S- （ubiquitin） E1-SH E2-SH E1-SH E1：activiting enzyme E2：carrier protein E3：ligase ubiquitinational protein ATP 19S regulate substrate ATP 20S Proteasome 26S Proteasome

II. Amino acids Degradation

The catabolism of amino acids

I. Deamination A. Transamination B. Oxidative deamination C. Combined Deamination

A. Transamination Transamination by Aminotransferase (transaminase) always involve PLP coenzyme (pyridoxal phosphate) reaction goes via a Schiff’s base intermediate all transaminase reactions are reversible

Transamination aminotransferases

B. Oxidative Deamination L-glutamate dehydrogenase (in mitochondria)

C. Combined Deamination 1. Transamination + Oxidative Deamination ?

2. Transamination + purine nucleotide cycle NH3 AA Asp -Keto glutarate IMP H2O aminotransferases AST 2. Transamination + purine nucleotide cycle AMP -Keto acid Oxaloacetate fumarate malate

II. Decarboxylation The decarboxylation of AAs produce some neurotransmitters’ precursors – bioactive amines

-aminobutyric acid (GABA) Glutamine can be decarboxylated in a similar PLP-dependent fashion, outputting -aminobutyric acid (neurotransmitter, GABA) L-Glu decarboxylase – CO2 GABA L-Glu

Histidine decarboxylase L-Histidine – CO2 Histidine decarboxylase Histamine 强烈的血管舒张剂。增加血管的通透性，降低血压，甚至死亡。 Histamine

III. The metabolism of α-ketoacid Biosynthesis of nonessential amino acids TCA cycle member + amino acid α-keto acid + nonessential amino acid A source of energy (10%) ( CO2+H2O ) Glucogenesis and ketogenesis

Fate of the C-Skeleton of Amino Acids

Ⅳ . ammonia metabolism Fix ammonia onto glutamate to form glutamine and use as a transport mechanism Transport ammonia by alanine-glucose cycle and Gln regeneration Excrete nitrogenous waste through urea cycle

Transportation of ammonia alaninie - glucose cycle * regenerate Gln

Alanine-Glucose cycle In the liver alanine transaminase tranfers the ammonia to α-KG and regenerates pyruvate. The pyruvate can then be diverted into gluconeogenesis. This process is refered to as the glucose-alanine cycle.

Gln regeneration

Urea synthesis Synthesis in liver (Mitochondria and cytosol) Excretion via kidney To convert ammonia to urea for final excretion

The urea cycle： 线粒体 尿素 胞 液 CO2 + NH3 + H2O 氨基甲酰磷酸 Pi 瓜氨酸 鸟氨酸 瓜氨酸 氨基酸 2ADP+Pi CO2 + NH3 + H2O 氨基甲酰磷酸 2ATP N-乙酰谷氨酸 线粒体 Pi 鸟氨酸 瓜氨酸 精氨酸代 琥珀酸 瓜氨酸 天冬氨酸 ATP AMP + PPi 氨基酸 草酰乙酸 苹果酸 α-酮戊 二酸 谷氨酸 α-酮酸 鸟氨酸 尿素 精氨酸 延胡索酸 胞 液

UREA CYCLE (liver) 1. Overall Reaction: NH3 + HCO3– + aspartate + 3 ATP + H2O  urea + fumarate + 2 ADP + 2 Pi + AMP + ppi 2. Requires 5 enzymes: 2 from mitochondria and 3 from cytosol

Regulation of urea cycle The intake of the protein in food：the intake↑↑urea synthesis AGA：CPS I is an allosteric enzyme sensitive to activation by N-acetylglutamate（AGA） which is derived from glutamate and acetyl-CoA. All intermediate products accelerate the reaction Rate-limiting enzyme of urea cycle is argininosuccinate synthetase(精氨酸代琥珀酸合成酶)

The Urea Cycle is Linked to the Citric Acid Cycle NH4+

III. Biosynthesis of Amino acids

Ammonium Ion Is Assimilated into Amino Acids Through Glutamate and Glutamine Major Ammonium ion carrier

Biosynthesis of Amino Acids