Introduction 介绍

Amino acids are organic compounds that consist of alpha carbon in the center, hydrogen (H), amino (-NH2), carboxyl (-COOH), and specific R (side chain) groups. One linear chain of amino acids is called a polypeptide, and one or more polypeptides make up a protein. There are 20 major types of amino acids found in proteins, of which the differences are the side chains (R groups) that contain various chemical structures. This R group gives each amino acid and, finally, each protein-specific characteristic. These features include size, shape, hydrophilicity, hydrophobicity, interactions, polarity, and pH level. Each of these characteristics is crucial for the stability of the proteins in the human body and environment.[1]
氨基酸是由中心的α碳、氢（H）、氨基（-NH 2）、羧基（-COOH）和特定的R（侧链）基团组成的有机化合物。一条线性氨基酸链称为多肽，一条或多条多肽组成蛋白质。蛋白质中有20种主要类型的氨基酸，其中的差异在于含有各种化学结构的侧链（R基团）。这个R基团赋予每个氨基酸，最后赋予每个蛋白质特异性特征。这些特征包括大小、形状、亲水性、疏水性、相互作用、极性和pH水平。这些特征中的每一个对于蛋白质在人体和环境中的稳定性都至关重要。[1]第一章

Issues of Concern 关心的问题

As building blocks of proteins, amino acids are essential for multiple biological processes, including cell growth, division, and metabolic signaling pathways.[2] Amino acid synthesis and degradation are tightly controlled via a plethora of mechanisms in physiological conditions. However, the dysregulation of pathways involved in amino acid biogenesis and catabolism have been characterized in multiple inborn metabolic disorders such as phenylketonuria (PKU), alkaptonuria, and maple syrup urine disease (MSUD).[3]
作为蛋白质的构建模块，氨基酸对于多种生物过程是必不可少的，包括细胞生长、分裂和代谢信号通路。[2]在生理条件下，氨基酸的合成和降解通过多种机制受到严格控制。然而，参与氨基酸生物合成和代谢紊乱的途径的失调已经在多种先天性代谢紊乱中表征，如苯丙酮尿症（PKU）、黑酸尿症和枫糖浆尿病（MSUD）。[3]第一章

Molecular Level  分子水平

The amino acids with nonpolar R groups include glycine (G, Gly, NH2-CH2-COOH), alanine (A, Ala, CH3-CH(NH2)-COOH), valine (V, Val, (CH3)2-CH-CH(NH2)-COOH), leucine (L, Leu, (CH3)2-CH-CH2-CH(NH2)-COOH), methionine (M, Met, CH3-S-(CH2)2-CH(NH2)-COOH ), isoleucine (I, Ile, CH3-CH2-CH(CH3)-CH(NH2)-COOH), phenylalanine (F, Phe, Ph-CH2-CH(NH2)-COOH), tyrosine (Y, Tyr, HO-Ph-CH2-CH(NH2)-COOH), and tryptophan (W, Trp, Ph-NH-CH=C-CH2-CH(NH2)-COOH). Gly, Ala, Val, Leu, Met, and Ile have aliphatic R groups, and Phe, Tyr, and Trp have aromatic R groups. The aliphatic or aromatic group makes the amino acids hydrophobic (also called "water fear") or group with no tendency to be close to aqueous solutions. The globular proteins will opportunistically bury the hydrophobic side chains inside the protein interior by folding into a three-dimensional shape in aqueous solutions.[4]
具有非极性R基团的氨基酸包括甘氨酸（G，Gly，NH 2-CH 2-COOH），丙氨酸（A，Ala，CH 3-CH（NH 2）-COOH），缬氨酸（V，瓦尔，（CH 3）2-CH-CH（NH 2）-COOH），亮氨酸（L，Leu，（CH 3）2-CH-CH 2-CH（NH 2）-COOH），蛋氨酸（M，Met，CH 3-S-（CH 2）2-CH（NH 2）-COOH），异亮氨酸（I，Ile，CH 3-CH 2-CH（CH 3）-CH（NH 2）-COOH），苯丙氨酸（F，Phe，Ph-CH 2-CH（NH 2）-COOH），酪氨酸（Y，Tyr，HO-Ph-CH 2-CH（NH 2）-COOH）和色氨酸（W，Trp，Ph-NH-CH= C-CH 2-CH（NH 2）-COOH）。Gly、Ala、瓦尔、Leu、Met和Ile具有脂族R基团，而Phe、Tyr和Trp具有芳族R基团。脂肪族或芳香族基团使氨基酸具有疏水性（也称为“怕水”）或不倾向于接近水溶液的基团。球状蛋白质将通过在水溶液中折叠成三维形状而将疏水侧链偶然地埋在蛋白质内部。[4]美国

The amino acids with polar uncharged R groups are serine (S, Ser, HO-CH2-CH(NH2)-COOH), threonine (T, Thr, CH3-CH(OH)-CH(NH2)-COOH), cysteine (C, Cys, HS-CH2-CH(NH2)-COOH), proline (P, Pro, NH-(CH2)3-CH-COOH), asparagine (N, Asn, H2N-CO-CH2-CH(NH2)-COOH) and glutamine (Q, Gln, H2N-CO-(CH2)2-CH(NH2)-COOH). The side chains of these amino acids possess functional spectrum groups. Most have one or more atoms, such as oxygen, nitrogen, or sulfur, with electron pairs, allowing hydrogen bonding to water or other molecules.[5]
具有极性不带电R基团的氨基酸是丝氨酸（S，Ser，HO-CH 2-CH（NH 2）-COOH）、苏氨酸（T，Thr，CH 3-CH（OH）-CH（NH 2）-COOH）、半胱氨酸（C，Cys，HS-CH 2-CH（NH 2）-COOH）、脯氨酸（P，Pro，NH-（CH 2）3-CH-COOH）、天冬酰胺（N，Asn，H2 N-CO-CH 2-CH（NH 2）-COOH）和谷氨酰胺（Q，Gln，H2 N-CO-（CH 2）2-CH（NH 2）-COOH）。这些氨基酸的侧链具有功能谱基团。大多数有一个或多个原子，如氧，氮或硫，电子对，允许氢键结合到水或其他分子。[5]《中国日报》

Also, aspartate (D, Asp, HOOC-CH2-CH(NH2)-COOH) and glutamate (E, Glu, HOOC-(CH2)2-CH(NH2)-COOH) are amino acids with negatively charged R groups. On the contrary, lysine (K, H2N-(CH2)4-CH(NH2)-COOH), arginine (R, Arg, HN=C(NH2)-NH-(CH2)3-CH(NH2)-COOH), and histidine (H, His, NH-CH=N-CH=C-CH2-CH(NH2)-COOH) are amino acids with positively charged R groups.[6][7]
此外，天冬氨酸（D，Asp，HOOC-CH 2-CH（NH 2）-COOH）和谷氨酸（E，Glu，HOOC-（CH 2）2-CH（NH 2）-COOH）是具有带负电荷的R基团的氨基酸。相反，赖氨酸（K，H2 N-（CH 2）4-CH（NH 2）-COOH）、精氨酸（R，Arg，HN=C（NH 2）-NH-（CH 2）3-CH（NH 2）-COOH）和组氨酸（H，His，NH-CH=N-CH= C-CH 2-CH（NH 2）-COOH）是具有带正电荷的R基团的氨基酸。[6][7]《中国日报》

The amino acids are linked with their neighbors in a specific order by covalent bonds, also known as peptide bonds. These particular bonds are the amide linkages that form when the amino group reacts with the carboxylate carbon connecting two amino acids. The free amino group at one end of the polypeptide is typically called the amino-terminal or N-terminal. In contrast, the open carboxyl group at the other end is labeled as the carboxyl-terminal or C-terminal. Protein sequences are written or read from the N-to-C terminal direction. The chains of the amino acids or progression of the amino acids distinguish exquisitely one protein from another. The organism's DNA is specific in coding a particular sequence of amino acids. Each protein consists of one or more polypeptide chains. Proteins are polymers of 50 or more amino acids, while peptides are shorter amino acid polymers. A protease, which is also known as peptidase or proteinase, is an enzyme that catalyzes proteolysis. This phenomenon is constituted by the breakdown of proteins into smaller polypeptides and, eventually, single amino acids. Proteases cleave the peptide bonds within proteins by hydrolysis, which is a chemical reaction where the water breaks bonds. Acids, alkalis, or enzymes may be employed to determine protein hydrolysis.[8][9]
氨基酸通过共价键（也称为肽键）以特定的顺序与其相邻氨基酸连接。这些特殊的键是当氨基与连接两个氨基酸的羧酸碳反应时形成的酰胺键。多肽一端的游离氨基通常称为氨基末端或N末端。相反，另一端的开放羧基被标记为羧基末端或C末端。蛋白质序列是从N端到C端方向写入或读取的。氨基酸的链或氨基酸的排列顺序将一种蛋白质与另一种蛋白质区分开来。生物体的DNA在编码特定的氨基酸序列方面是特异性的。每个蛋白质都由一条或多条多肽链组成。蛋白质是50个或更多个氨基酸的聚合物，而肽是更短的氨基酸聚合物。蛋白酶，也称为肽酶或蛋白酶，是催化蛋白水解的酶。 这种现象是由蛋白质分解成更小的多肽并最终分解成单个氨基酸构成的。蛋白酶通过水解来切割蛋白质内的肽键，水解是水破坏键的化学反应。酸、碱或酶可用于测定蛋白质水解。 [8][9]第一章

Function 功能

The general functions of amino acids include the involvement in protein synthesis, biosynthetic products, and metabolic energy. Essentially, there is a crucial difference between positive and negative nitrogen balance, which is critical for understanding amino acid metabolism. In a positive balance, the nitrogen consumed is more considerable than the nitrogen excreted, while in a negative balance, the nitrogen consumed is less than the nitrogen excreted. A positive balance denotes net protein synthesis. It occurs when the organism is recovering from starvation, growth, and pregnancy. In contrast, a negative balance entails mobilization of the amino acids, tissue necrosis, or a poor-quality condition of the human body as a consequence of 3rd-degree burns or significant surgical operations. [10][11]
氨基酸的一般功能包括参与蛋白质合成、生物合成产物和代谢能量。从本质上讲，正氮平衡和负氮平衡之间存在着至关重要的差异，这对于理解氨基酸代谢至关重要。在正平衡中，消耗的氮比排泄的氮更可观，而在负平衡中，消耗的氮比排泄的氮少。正平衡表示净蛋白质合成。它发生在有机体从饥饿，生长和怀孕中恢复时。相反，负平衡需要氨基酸的动员，组织坏死，或由于三度烧伤或重大外科手术导致的人体质量差的状况。[10][第十一届]

The amino acids subdivide into essential and non-essential. There are amino acids that need to be obtained directly (diet) and amino acids that can be synthesized by the organism. The amino acids the human body cannot produce are called essential amino acids, which contain His, Ile, Leu, Lys, Met, Val, Phe, Thr, and Trp. The human body gets these nine essential amino acids from food or nutritional supplement. In specific medical conditions or at different ages, the other amino acids may be conditionally essential for the human body.[12]
氨基酸又分为必需氨基酸和非必需氨基酸。有需要直接获得的氨基酸（饮食）和可以由生物体合成的氨基酸。人体不能产生的氨基酸称为必需氨基酸，其中包括His、Ile、Leu、LyS、Met、瓦尔、Phe、Thr和Trp。人体从食物或营养补充剂中获得这九种必需氨基酸。在特定的医学条件下或在不同的年龄，其他氨基酸可能是人体有条件必需的。[12个]

Glutamate is a non-essential amino acid that can be synthesized from alpha-ketoglutaric acid in the Krebs or citric acid cycle. In the brain and spinal cord, glutamate is synthesized from glutamine as part of the glutamate-glutamine cycle by the enzyme glutaminase. Glutamate cannot cross the blood-brain barrier unaided and serves as a metabolic precursor for the neurotransmitter gamma-aminobutyric acid (GABA) via the action of glutamate decarboxylase.[13]
谷氨酸是一种非必需氨基酸，可以在克雷布斯或柠檬酸循环中由α-酮基谷氨酸合成。在大脑和脊髓中，谷氨酸是由谷氨酰胺合成的，作为谷氨酸-谷氨酰胺循环的一部分，由谷氨酸脱氢酶合成。谷氨酸不能单独穿过血脑屏障，并通过谷氨酸脱羧酶的作用作为神经递质γ-氨基丁酸（GABA）的代谢前体。[13个国家]

Methionine is converted to S-adenosylmethionine (SAM) by methionine adenosyltransferase. Loss of methionine has correlated with an accumulation of hydrogen peroxide (H2O2) in hair follicles, a decrease in tyrosinase effectiveness, and a gradual loss of the natural hair color.[14] Methionine is crucial for the increase in the intracellular concentration of glutathione (GSH). GSH is an antioxidant found in animals, plants, fungi, bacteria, and archaea. Promoting antioxidant-mediated cell defense and redox regulation is critical in protecting cells against dopamine-induced nigral cell loss by oxidative binding metabolites.[15] Methionine is an amino acid, an intermediate component for the biosynthesis of some amino acids. These amino acids are cysteine, carnitine, taurine, lecithin, and phosphatidylcholine. Also, methionine is medium in the biosynthesis of additional phospholipids. Improper transformation of methionine can lead to atherosclerosis due to the accumulation of homocysteine. Moreover, this amino acid is essential to reversing the damaging methylation of the glucocorticoid receptor gene caused by repeated stress exposures, with implications for depression.[16]
甲硫氨酸通过甲硫氨酸腺苷转移酶转化为S-腺苷甲硫氨酸（SAM）。甲硫氨酸的损失与过氧化氢（H2 O2）在毛囊中的积累，酪氨酸酶有效性的降低和自然发色的逐渐丧失有关。[14]甲硫氨酸对谷胱甘肽（GSH）细胞内浓度的增加至关重要。GSH是一种抗氧化剂，存在于动物、植物、真菌、细菌和古细菌中。促进抗氧化剂介导的细胞防御和氧化还原调节在保护细胞免受氧化结合代谢物引起的多巴胺诱导的黑质细胞损失中至关重要。[15]蛋氨酸是一种氨基酸，是某些氨基酸生物合成的中间组分。这些氨基酸是半胱氨酸、肉毒碱、牛磺酸、卵磷脂和磷脂酰胆碱。此外，甲硫氨酸在其他磷脂的生物合成中是中等的。甲硫氨酸的不适当转化可由于同型半胱氨酸的积累而导致动脉粥样硬化。 此外，这种氨基酸对于逆转由反复压力暴露引起的糖皮质激素受体基因的破坏性甲基化至关重要，这与抑郁症有关。 [16个]

Glycine is considered to be not essential to the human diet. The body can synthesize this amino acid from the amino acid serine. However, the metabolic capacity for glycine biosynthesis does not satisfy the need for collagen synthesis in several organisms. In the liver of some of them at the vertebrate level, glycine synthesis is catalyzed by glycine synthase, which is also known as glycine cleavage enzyme. Glycine is integral to the creation of alpha-helices in secondary protein structure, and, mainly, it is the most copious amino acid in collagen harboring triple-helices. Glycine is also an inhibitory neurotransmitter. The interference of its release within the central nervous system (spinal cord) can induce spastic paralysis due to uninhibited muscle contraction.[17]
甘氨酸被认为不是人类饮食所必需的。人体可以从丝氨酸合成这种氨基酸。然而，甘氨酸生物合成的代谢能力不能满足几种生物体中胶原蛋白合成的需要。在脊椎动物的肝脏中，甘氨酸合成是由甘氨酸合成酶催化的，甘氨酸合成酶也被称为甘氨酸裂解酶。甘氨酸对于蛋白质二级结构中α-螺旋的产生是不可或缺的，并且主要地，它是含有三螺旋的胶原蛋白中最丰富的氨基酸。甘氨酸也是一种抑制性神经递质。干扰其在中枢神经系统（脊髓）内的释放可由于不受抑制的肌肉收缩而引起痉挛性麻痹。[17个]

Mechanism 机制

Amino acids are synthesized through different pathways. Cys is synthesized from Met, while Tyr synthesis can occur using Phe, considering that the amino acid precursors can be available in the body. The amino acid Arg, which arises from the urea cycle, is considered "semi-essential" because the synthetic capacity of the human body is limited. Non-essential amino acids need their precursors, which must be available in the organism. Specifically, Ala and Gly's amino acids need pyruvate to be synthesized, while aspartic acid and Asn rely on oxaloacetic acid (OAA). Thus, six essential amino acids and three non-essential are integrated from oxaloacetate and pyruvate.[18]
氨基酸是通过不同的途径合成的。Cys由Met合成，而Tyr合成可以使用Phe进行，考虑到氨基酸前体可以在体内获得。由尿素循环产生的氨基酸Arg被认为是“半必需的”，因为人体的合成能力是有限的。非必需氨基酸需要其前体，而这些前体必须在生物体中存在。具体地，Ala和Gly的氨基酸需要丙酮酸来合成，而天冬氨酸和Asn依赖于草酰乙酸（OAA）。因此，从草酰乙酸和丙酮酸中整合了六种必需氨基酸和三种非必需氨基酸。[18个国家]

The transamination from Glu is vital in forming Asp and Ala from OAA and pyruvate. Asp is crucial in synthesizing Asn, Met, Lys, and Thr. OAA is critical because no Asp would form without it. The alpha-ketoglutaric acid or 2-oxoglutaric acid is one of two ketone derivatives of glutaric acid. Its anion, alpha-ketoglutarate (alpha-KG), also known as 2-oxoglutarate, is a biological compound of paramount importance. It is the keto acid produced by the deamination of Glu and is an intermediate compound in the urea or Krebs cycle. The amino acids glutamic acid and Gln arise from alpha-KG.[19]
谷氨酸的转氨作用对OAA和丙酮酸形成天冬氨酸和丙氨酸至关重要。Asp在合成Asn、Met、Lys和Thr中至关重要。α-酮基谷氨酸或2-酮基谷氨酸是谷氨酸的两种酮衍生物之一。它的阴离子α-酮戊二酸（alpha-KG），也称为2-酮戊二酸，是一种非常重要的生物化合物。它是由谷氨酸脱氨基产生的酮酸，是尿素或克雷布斯循环中的中间化合物。氨基酸谷氨酸和谷氨酰胺来自α-KG。[19个]

Finally, the amino acid Pro derives from Glu, while Ser is from 3-phosphoglyceric acid (3PG). The 3PG is the conjugate acid of glycerate 3-phosphate. It is a biochemically significant metabolic intermediate in glycolysis and the Calvin cycle. In the Calvin cycle or photosynthetic carbon reduction (PCR) cycle of photosynthesis, 3PG is vital. It is the product of the spontaneous scission of an unstable 6-carbon intermediate formed upon CO fixation. Thus, glycerate 3-phosphate is a precursor for Ser, which, in turn, can create Cys and Gly through the homocysteine cycle. Therefore, Pro arises from Glu, while Ser is from 3PG. In the transamination reaction, an amino acid (Ala or Asp) exchanges its amine group for the oxy group in alpha-KG. The products are Glu and pyruvate or OAA (from Ala or Asp, accordingly).[19][20]
最后，氨基酸Pro来自Glu，而Ser来自3-磷酸甘油酸（3 PG）。3 PG是甘油酸3-磷酸的共轭酸。它是糖酵解和卡尔文循环中的生化重要代谢中间体。在光合作用的卡尔文循环或光合碳还原（PCR）循环中，3 PG至关重要。它是CO固定后形成的不稳定的6-碳中间体自发断裂的产物。因此，甘油酸3-磷酸是丝氨酸的前体，而丝氨酸又可以通过同型半胱氨酸循环产生Cys和Gly。因此，Pro来自Glu，而Ser来自3 PG。在转氨反应中，氨基酸（Ala或Asp）将其胺基交换为alpha-KG中的氧基。产物是Glu和丙酮酸或OAA（相应地来自Ala或Asp）。[19][20个]

Different proteases can degrade proteins into many small peptides or amino acids by hydrolyzing their peptide bonds. The unused amino acids may degrade further to join several metabolic processes. At first, the amino acids deaminate to their metabolic intermediates. This process is helpful for the excretion of an excessive amount of nitrogen. Subsequently, they can transform into the remaining carbon skeleton. In particular, this deamination process contains two steps. The first part uses deamination. In this step, the aminotransferase catalyzes the -NH2 group of the amino acid to alpha-KG. After that, it produces Glu and a novel alpha-keto acid of the specific amino acid. The Glu -NH2 group could then be transferred to OAA to form alpha-KG and Asp. This trans-amination series only degrade the primary amino acid, while the -NH2 group nitrogen does not exclude. There is an alternative pathway, using NADP or NAD+ as the oxidizing agent, and Glu dehydrogenase deaminates Glu. Then, it produces ammonia and alpha-KG.
不同的蛋白酶可以通过水解蛋白质的肽键将蛋白质降解成许多小肽或氨基酸。未使用的氨基酸可进一步降解以加入几个代谢过程。首先，氨基酸脱氨成为它们的代谢中间产物。这个过程有助于排出过量的氮。随后，它们可以转化为剩余的碳骨架。特别地，该脱氨基过程包括两个步骤。第一部分使用脱氨。在该步骤中，氨基转移酶催化氨基酸的-NH 2基团转化为α-KG。之后，它产生Glu和特定氨基酸的新型α-酮酸。然后，Glu-NH 2基团可以转移到OAA以形成α-KG和Asp。这种转氨作用系列仅降解伯氨基酸，而-NH 2基团氮不排除。存在替代途径，使用NADP或NAD+作为氧化剂，并且Glu脱氢酶使Glu脱氨基。 然后，它产生氨和α-KG。

In the evaluation of the biochemistry of the amino acids, seven metabolic intermediates of the aminoacidic degradation platform are paramount. They include acetyl-CoA, pyruvate, alpha-KG, acetoacetate, fumarate, succinyl-CoA, and OAA. In the most updated classification, Leu, Ile, Thr, and Lys degrade to acetyl-CoA, while Cys, Ala, Thr, Gly, Trp, and Ser degrade to pyruvate. Glu, Arg, His, Pro, and Gln degrade to alpha-KG, while Lys, Leu, Trp, Tyr, and Phe break down to acetoacetate. Finally, Tyr, Phe, and Asp degrade to fumarate, Val, Met, and Ile break down to succinyl-CoA, and Asp and, of course, Asn degrade to OAA. Isoleucine is an essential nutrient because it is unsynthesized in the body. This amino acid is both a glucogenic and ketogenic amino acid. In microorganisms and plants, it is synthesized via several steps beginning with pyruvate and alpha-ketobutyrate. The enzymes involved in this biosynthesis include acetolactate synthase, acetohydroxy acid isomeroreductase, dihydroxy acid dehydratase, and valine aminotransferase.[21]
在氨基酸的生物化学评价中，氨基酸降解平台的7种代谢中间体至关重要。它们包括乙酰辅酶A、丙酮酸、α-KG、乙酰乙酸、富马酸、琥珀酰辅酶A和OAA。在最新的分类中，Leu、Ile、Thr和Lys降解为乙酰辅酶A，而Cys、Ala、Thr、Gly、Trp和Ser降解为丙酮酸。Glu、Arg、His、Pro和Gln降解为α-KG，而Lys、Leu、Trp、Tyr和Phe分解为乙酰乙酸。最后，Tyr、Phe和Asp降解为富马酸，瓦尔、Met和Ile分解为琥珀酰辅酶A，Asp和Asn降解为OAA。异亮氨酸是一种必需的营养素，因为它在体内是不合成的。该氨基酸既是生糖氨基酸又是生酮氨基酸。在微生物和植物中，它是从丙酮酸和α-酮丁酸开始通过几个步骤合成的。 参与这种生物合成的酶包括乙酰乳酸合酶、乙酰羟酸异构还原酶、二羟酸脱氢酶和缬氨酸氨基转移酶。 [21日]

Testing 测试

In clinical practice, plasma or urine amino acids undergo testing to evaluate patients with possible inborn metabolism problems. They can also assess many diseases, such as liver diseases, endocrine disorders, muscular diseases, neurological disorders, neoplastic diseases, renal failure, burns, and nutritional disturbances. Both high-performance liquid chromatography (HPLC) and gas chromatography (GC) have been used to quantitatively identify the plasma or urine amino acids in clinical settings.[22][23] Currently, capillary electrophoresis (CE), liquid chromatography with tandem mass spectrometry (LC-MS-MS), nuclear magnetic resonance (NMR) methods, and a chip-type miniaturization technology are also useful to detect amino acids in the laboratory.[24][25][26][27]
在临床实践中，血浆或尿液中的氨基酸进行测试，以评估可能与先天性代谢问题的患者。它们还可以评估许多疾病，如肝脏疾病、内分泌失调、肌肉疾病、神经系统疾病、肿瘤疾病、肾衰竭、烧伤和营养失调。高效液相色谱法（HPLC）和气相色谱法（GC）已被用于在临床环境中定量鉴定血浆或尿液中的氨基酸。[22][23]目前，毛细管电泳（CE），液相色谱串联质谱（LC-MS-MS），核磁共振（NMR）方法和芯片型微型化技术也可用于在实验室中检测氨基酸。[24][25] [26]第二十六话

Clinical Significance 临床意义

Amino acid disorders are identifiable at any age; most of them become evident during infancy or early childhood. Many inborn amino metabolism diseases occur in infancy or childhood. These disorders may include cystinuria, histidinemia, phenylketonuria (PKU), methyl-malonyl CoA mutase deficiency (MCM deficiency), albinism, and tyrosinemia. Other amino acid disorders may be encountered later in life, including homocystinuria, alkaptonuria, maple syrup urine disease (MSUD), and cystathioninuria. These disorders lead to clinical symptoms or signs of the specific amino acid disorder, which results in the deficiency or accumulation of one or more amino acids in the body's biological fluids, such as plasma or urine. [3]
氨基酸紊乱在任何年龄都是可以识别的;其中大多数在婴儿期或幼儿期变得明显。许多先天性氨基代谢疾病发生在婴儿或儿童时期。这些病症可包括胱氨酸尿症、组氨酸血症、苯丙酮尿症（PKU）、甲基丙二酰辅酶A缺乏症（MCM缺乏症）、白化病和酪氨酸血症。其他氨基酸紊乱可能在以后的生活中遇到，包括同型胱氨酸尿症，黑酸尿症，枫糖浆尿病（MSUD）和胱硫醚尿症。这些病症导致特定氨基酸病症的临床症状或体征，其导致一种或多种氨基酸在身体的生物流体如血浆或尿中缺乏或积累。[3]第一章

The deficiency of Phe hydroxylase causes PKU. Currently, there are more than 400 mutations have been identified in the gene related to the cause of PKU.[28] This disease is usually heterozygous. Besides, the deficiency of enzymes such as dihydropteridine reductase (DHPR) or tetrahydrobiopterin (BH4) synthesis enzymes also leads to hyperphenylalaninemia.[29][30] The BH4 or generated product replacement therapy treats this enzyme deficiency-related PKU. In the case of the classic PKU, the Phe, phenyl lactate, phenylpyruvate, and phenylacetate are increased in the plasma, urine as well as other tissue samples. The phenyl pyruvic acid excreted in urine produces a "mousy" odor. Central nervous system symptoms, such as mental retardation, seizures, failure to walk or speak, tremors, and hyperactivity, also show in these patients. Another characteristic of classic PKU is hypopigmentation, which is due to the deficiency in the formation of melanin, which leads to pigmentation deficiency. Usually, the patients show light skin, fair hair, and blue eyes. Temporally, low Phe content synthetic nutrient supplemented with Tyr is the treatment of the classic PKU.
苯丙氨酸羟化酶的缺乏导致苯丙酮尿症。目前，在与PKU病因相关的基因中已经确定了400多个突变。[28]这种疾病通常是杂合子。此外，酶如二氢蝶啶还原酶（DHPR）或四氢生物蝶呤（BH 4）合成酶的缺乏也导致高苯丙氨酸血症。[29][30] BH4或生成的产品替代疗法治疗这种酶缺乏相关的PKU。在经典PKU的情况下，血浆、尿液以及其他组织样品中的Phe、乳酸苯酯、丙酮酸苯酯和乙酸苯酯增加。尿液中排出的苯丙氨酸会产生一种“恶臭”气味。中枢神经系统症状，如智力迟钝，癫痫发作，不能行走或说话，震颤和多动症，也显示在这些患者。经典PKU的另一个特征是色素减退，这是由于黑色素形成不足，导致色素缺乏。 通常，患者表现为浅色皮肤，金发和蓝眼睛。从时间上看，补充Tyr的低Phe含量合成营养素是经典PKU的治疗方法。

Albinism is a congenital disorder that is the defect of Tyr metabolism leading to a deficiency in melanin production. The characteristics of albinism are hypopigmentation by the total or partial absence of pigment in the hair, skin, and eyes. There is no cure for albinism because it is a genetic disorder.[31] At the moment, getting proper eye care, such as using sunglasses to prevent the ultraviolet (UV) rays damage from the sun and monitoring for signs of abnormalities of the skin, is the treatment of albinism.
白化病是一种先天性疾病，其是Tyr代谢缺陷导致黑色素产生不足。白化病的特点是色素减退的全部或部分缺乏色素的头发，皮肤和眼睛。白化病是一种遗传性疾病，因此无法治愈。[31]目前，获得适当的眼睛护理，如使用太阳镜，以防止紫外线（UV）从太阳和监测皮肤异常的迹象损害，是白化病的治疗。

Alkaptonuria is a rare disease with homogentisic acid oxidase defect, an enzyme in the Tyr degradation pathway. The urine specimen of the alkaptonuria patient shows some darkening on the surface after standing for fifteen minutes, which is due to homogentisate acid oxidation. And after two hours of standing, the patient's urine is entirely black. The characteristics of alkaptonuria include the accumulation of homogentisic aciduria, large joint arthritis, and the intervertebral disks of vertebrae deposit with dense black pigments.[32] A low protein diet with small in Phe and Tyr is the treatment of alkaptonuria, which helps reduce the homogentisic acid levels.
尿黑酸是一种罕见的尿黑酸氧化酶缺陷的疾病，尿黑酸氧化酶是酪氨酸降解途径中的一种酶。黑尿症患者的尿液标本在静置15分钟后显示表面上的一些变暗，这是由于尿黑酸氧化。两个小时后，病人的尿液完全是黑色的。黑酸尿症的特征包括尿黑酸尿的积累、大关节炎和椎骨的椎间盘存款有致密的黑色色素。[32]苯丙氨酸和酪氨酸含量低的低蛋白饮食是黑酸尿症的治疗方法，有助于降低尿黑酸水平。

Tyrosinemia type 1 results from a deficiency in fumarylacetoacetate hydrolase, leading to the accumulation of fumarylacetoacetate and its metabolites (especially succinylacetone) in urine, which makes cabbage-like odor. The patients show renal tubular acidosis and liver failure.[33] The treatment is Phe and Tyr restriction dietary.
1型酪氨酸血症是由于富马酰乙酰乙酸水解酶缺乏，导致富马酰乙酰乙酸及其代谢产物（特别是琥珀酰丙酮）在尿液中积累，从而产生卷心菜样气味。患者表现为肾小管性酸中毒和肝功能衰竭。[33]治疗是限制Phe和Tyr饮食。

MCM deficiency is a disease due to the defect of methyl malonyl CoA mutase, which catalyzes isomerization between methyl malonyl-CoA and succinyl-CoA in the pathway.[34] It shows high levels of methyl malonyl CoA in the blood samples from the patients. Symptoms of MCM deficiency include vomiting, dehydration, fatigue, hypotonia, fever, breathing difficulty, and infections. Also, metabolic acidosis and developmental delay occur as long-term complications. The treatment of MCM deficiency includes a special diet with low proteins (low in Ile, Met, Thr, and Val amino acids) and certain fats but high in calories.
MCM缺乏症是由于甲基丙二酰辅酶A β缺陷引起的疾病，甲基丙二酰辅酶A β在途径中催化甲基丙二酰辅酶A和琥珀酰辅酶A之间的异构化。[34]结果显示病人血液样本中甲基丙二酰辅酶A含量很高。MCM缺乏症的症状包括呕吐、脱水、疲劳、肌张力减退、发烧、呼吸困难和感染。此外，代谢性酸中毒和发育迟缓也是长期并发症。MCM缺乏症的治疗包括低蛋白（Ile、Met、Thr和瓦尔氨基酸含量低）和某些脂肪但高热量的特殊饮食。

Maple syrup urine disease (MSUD) is a rare autosomal recessive disease with a partial or complete defect of branched-chain alpha-keto acid dehydrogenase. The enzyme can decarboxylate Leu, Ile, and Val. This deficiency leads to the accumulation of branched-chain alpha-keto acid substrates. These three amino acids cause functional abnormalities in the brain. The urine with a classic maple syrup odor is a hallmark characteristic of MSUD. MSUD patients show symptoms such as vomiting, feeding difficulties, dehydration, and severe metabolic acidosis.[35]
枫糖浆尿病（MSUD）是一种罕见的常染色体隐性遗传病，具有支链α-酮酸脱氢酶的部分或完全缺陷。该酶可使Leu、Ile和瓦尔脱羧。这种缺陷导致支链α-酮酸底物的积累。这三种氨基酸会导致大脑功能异常。带有典型枫糖浆气味的尿液是MSUD的标志性特征。MSUD患者表现出呕吐、进食困难、脱水和严重代谢性酸中毒等症状。[35]第三十五届 

In the clinic, a synthetic formula containing a limited amount of Leu, Ile, and Val is the suggested therapy for MSUD infants. MSUD (OMIM #248600) demonstrates a disturbance of the regular activity of the branched-chain α-ketoacid dehydrogenase (BCKAD) complex, the second step in the catabolic trail for the branched-chain amino acids (BCAAs) that includes leucine, isoleucine, and valine. MSUD can occur early in life, but late-onset MSUD is also common and include neurologic symptoms. These symptoms may include inappropriate, extreme, or erratic behavior and moods, hallucinations, oscillating hypertonia/hypotonia, ataxia, seizures, opisthotonos, and coma.
在临床上，含有有限量的Leu、Ile和瓦尔的合成配方是MSUD婴儿的建议疗法。MSUD（OMIM #248600）证明了支链α-酮酸脱氢酶（BCKAD）复合物的常规活性紊乱，这是支链氨基酸（BCAA）分解代谢途径的第二步，包括亮氨酸、异亮氨酸和缬氨酸。MSUD可以在生命早期发生，但迟发性MSUD也很常见，包括神经系统症状。这些症状可能包括不适当、极端或不稳定的行为和情绪、幻觉、振荡性张力亢进/张力减退、共济失调、癫痫发作、角弓反张和昏迷。

Cystathioninuria is a rare autosomal recessive metabolic disorder due to a deficiency in cystathionase. It links with the lower activity of the enzyme cystathionase. There are two types of primary cystathioninuria based on the inherited mutation of the CTH gene: vitamin B6 responsive and vitamin B6 unresponsive cystathioninuria.[36][37] It is characterized by the accumulation of cystathionine and its metabolites in plasma and urine, but no clinical symptoms are present. The treatment of cystathioninuria varies according to the category in different cystathioninuria patients. Increased consumption of vitamin B6 is considered the best treatment for the active form of vitamin B6.[38]
胱硫醚尿症是一种罕见的常染色体隐性遗传代谢紊乱，由于缺乏胱硫醚酶。这与胱硫醚酶的低活性有关。基于CTH基因的遗传突变，存在两种类型的原发性胱硫醚尿症：维生素B6反应性和维生素B6无反应性胱硫醚尿症。[36][37]其特征是胱硫醚及其代谢物在血浆和尿液中蓄积，但不存在临床症状。胱硫醚尿症的治疗根据不同胱硫醚尿症患者的类别而不同。增加维生素B6的摄入量被认为是维生素B6活性形式的最佳治疗方法。[38个]

Homocystinuria is an inherited disorder due to the defect of the metabolism of Met amino acid. The most common cause is the enzyme cystathionine beta-synthetase deficiency, which results in the elevation of Met and homocysteine and low levels of Cys in plasma and urine.[39] The characteristics of homocystinuria include displacement of the lens of the eye, skeletal abnormalities, osteoporosis, premature arterial disease, and mental delay.[40][41] The treatment of homocystinuria involves the restriction of Met intake and supplementation with folate, vitamin B6, and B12.[42]
同型胱氨酸尿症是一种遗传性疾病，由于代谢缺陷的蛋氨酸氨基酸。最常见的原因是胱硫醚β-合成酶缺乏，这导致血浆和尿液中Met和同型半胱氨酸水平升高以及Cys水平降低。[39]同型胱氨酸尿症的特征包括眼透镜移位、骨骼异常、骨质疏松、早发性动脉疾病和智力发育迟缓。[40][41]同型胱氨酸尿症的治疗包括限制Met摄入和补充叶酸，维生素B6和B12。[第四十二届]

Histidinemia is a rare autosomal recessive inborn metabolic error due to the defect of the enzyme histidase.[43] It characteristically demonstrates high levels of His, histamine, and imidazole in blood, urine as well as cerebrospinal fluid. A low in His intake diet is suggested for treating histidinemia, though the restricted diet is unnecessary for most cases.[44]
组氨酸血症是一种罕见的常染色体隐性遗传性先天性代谢异常，由于酶的缺陷组氨酸。[43]其特征性表现为血液、尿液以及脑脊液中高水平的组氨酸、组胺和咪唑。低组氨酸摄入量的饮食建议用于治疗组氨酸血症，尽管大多数情况下限制饮食是不必要的。[第四十四届]

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Disclosure: Fan Shen declares no relevant financial relationships with ineligible companies.

Disclosure: Consolato Sergi declares no relevant financial relationships with ineligible companies.