慢性肾衰竭患者血液透析前后氨基酸谱和蛋白质水平的变化

目的：观察慢性肾衰竭（CRF）患者血液透析（HD）前后血清蛋白质和氨基酸（AA）谱变化。方法：对20例CRF患者HD前后蛋白质和氨基酸浓度进行比较。结果：透析后血清视黄醇结合蛋白（RBP）、白蛋白（Alb)和前白蛋白（PA）较透析前有所下降，而转铁蛋白有所增高，但均无统计学意义。血清丝氨酸（Ser)、苏氨酸（Thr)、谷氨酸（Glu)、脯氨酸（Pro)、甘氨酸（Gly)、丙氨酸（Ala)、半胱氨酸（Cys)、赖氨酸（Lys)浓度，透析后下降显著（P＜0．01），余无显著性改变。结论：HD影响机体蛋白质、氨基酸代谢，可使部分血清氨基酸蛋白质丢失，加重机体营养不良。     

烧伤患者血、红细胞内游离氨基酸的变化及输入氨基酸对其变化的影响

目的动态观察大面积烧伤患者血浆及红细胞内游离氨基酸含量的变化,比较其变化模型,并探讨外源性输入氨基酸后对血及红细胞内游离氨基酸浓度的影响,为临床烧伤患者氨基酸输液提供依据.方法44例烧伤患者,年龄19～50岁,其中烧伤后未输氨基酸患者25例,烧伤总面积(51.9±24.2)%,Ⅲ度面积15.8%.烧伤后输氨基酸注射液患者19例,烧伤面积(60.4±19.3)%,Ⅲ度面积23.9%,烧伤后第3天输入北京制药厂生产的复合氨基酸注射液,每天输入500～750ml.伤后1、3、7、14和21d清晨采血处理样品,置-30℃冰箱存放待测.以835-50型氨基酸自动分析仪测定氨基酸含量,并以20例献血者血浆及红细胞内游离氨基酸含量作对照分析.结果检测结果显示烧伤后血浆游离氨总含量显著降低(P＜0.05～0.01);苯丙、赖氨酸和苯丙/酪比值在伤后显著升高(P＜0.05～0.01);色、组、精、丙、甘、苏、脯和丝氨酸显著降低(P＜0.05～0.01),但3d后基本回升至对照组水平.烧伤后患者红细胞内总游离氨基酸和大多数游离氨基酸含量的动态变化与血浆游离氨基酸含量的动态变化基本相似.红细胞内色、蛋、精和脯氨酸浓度很低或未测出,并未见红细胞内苯丙/酪氨酸比值显著升高.与烧伤未输复合氨基酸患者比较,输入外源性氨基酸患者未见显著改变血浆和红细胞内游离氨基酸含量.讨论研究结果提示,红细胞内游离氨基酸浓度显著高于血浆浓度,但是其烧伤后的游离氨基酸变化趋势与烧伤后血浆变化趋势基本相似;外源性输入本研究所给予的复合氨基酸含量后未见明显改变烧伤患者血浆和红细胞内游离氨基酸浓度.     

烧伤对兔血红细胞内游离氨基酸浓度的影响

目的为了解烧伤后游离氨基酸库的变化,动态观察烧伤兔红细胞内游离氨基酸的代谢变化.方法以日立835-50型氨基酸自动分析仪测定兔30%TBSAⅢ°烧伤后1、3、7、15和20d血红细胞内游离氨基酸的含量.结果烧伤后多数测试点红细胞内游离氨基酸不同程度降低;伤后1天苏、丝、甘、丙、胱、缬、蛋、异亮、赖、精、脯和总氨基酸浓度显著降低(P＜0.05～0.01);苏、丙、缬、组、精和脯氨酸伤后各个时间点均降低,个别时间点显著降低(P＜0.05～0.01).结论烧伤后红细胞内游离氨基酸依靠易化扩散参与全身氨基酸的再分布.     

脓毒症大鼠血浆游离氨基酸浓度的变化

目的 探讨脓毒症早期大鼠血浆游离氨基酸含量的变化与骨骼肌蛋白降解间的关系。方法 以腹腔注射内毒素建立大鼠脓毒症模型,将动物随机分为正常对照组和内毒素攻击后2、6、12、24h共5组,每组8只动物。用氨基酸自动分析仪的生理体液柱测定各组大鼠血游离氨基酸含量;用全自动生化分析仪测定血浆谷丙转氨酶（ALT）和谷草转氨酶（AST）浓度;用放射免疫分析（RIA）法测定血浆皮质醇含量;用酰联免疫吸附试验（ELISA）测定血浆TNF－α和IL－6含量。结果 内毒素攻击后各时相点大鼠血浆总氨基酸含量在正常范围内波动;支链氨基酸（BCAA）在2、6、12h降低,24h则出现显著升高,亮氨酸、异亮氨酸无显著怀变化,缬氨酸早期明显降低,后期则上升;芳香族氨基酸（AAA）在各时相点不同程度升高,2h和6h显著升高,酪氨酸12h降低,苯丙氨酸在各时相点均显著升高;苯丙氨酸／酪氨酸（Phe/Tyr)比值内毒素攻击后各时相点均出现显著增加;BCAA／AAA比值在2h和6h较正常显著较低;苏氨酸、谷氨酸、鸟氨酸、3－甲基组氨酸（3－MH）、组氨酸、丙氨酸早期升高或大多数时相点显著升高,赖氨酸、肌氨酸、胱氨酸和磷酸丝氨酸在内毒素攻击后无显著性变化,其它氨基酸均见不同程度的降低或显著降低。血浆ALT、AST浓度在内毒素攻击后各时相点显著升高（P＜0．01）,6h达峰值。血浆皮质醇含量在各时相点均显著升高（P＜0．01）,6h达峰值。血浆TNF－α和IL－6含量均上升（P＜0．01）,其中TNF-α于2h达峰值,IL－6于12h达峰值。结论 脓毒症大鼠血浆游离氨基酸浓度变化主要由于骨骼肌蛋白降解增强与肝脏代谢负担加重所致。     

术后应用α-酮戊二酸保护骨骼肌蛋白质合成和游离谷氨酰胺水平

骨骼肌组织是体内最大的游离氨基酸池。创伤后肌细胞内游离氨基酸变化特征为分解代谢。谷氨酸胺(Gln)和基础氨基酸浓度下降,支链氨基酸和芳香氨基酸浓度增加。肌内游离Gln浓度在创伤后12小时开始降低,第3天Gln最明显,给予不含Gln的全静脉营养(TPN)不能改善,TPN中加入α-酮戊二酸(AKG)可减少骨骼肌Gln的丢失,改善氮平衡。AKG可提供碳链骨架,有利于氮平衡和蛋白质合成。作者对21例择期胆囊切除患者,术后给予     

谷氨酰胺与肿瘤

谷氨酰胺与肿瘤第二军医大学长海医院普外科（上海，２００４３３）刘连杰综述屠岳，叶必远审阅谷氨酰胺（ｇｌｕｔａｍｉｎｅ，ＧＬＮ）对正常机体是一种非必需氨基酸，占体内游离氨基酸池的６０％，正常血浆中浓度为０．６～０．９ｍｍｏｌ／Ｌ，可在细胞内氧化供能并为...     

富含谷氨酰胺和支链氨基酸的肠外制剂对创伤大鼠的效用

目的研究普通氨基酸注射液(17AA)与富含谷氨酰胺及支链氨基酸注射液(20AA)对创伤大鼠的营养效用.方法以Wistar大鼠为创伤模型,分别输注两种配方的氨基酸注射液,以日立L-8500氨基酸自动分析仪测定动物血浆游离氨基酸,并测定创伤处海绵内羟脯氨酸含量.结果显示创伤后大鼠血浆牛磺酸、谷氨酸、谷氨酰胺和支链氨基酸含量较术前下降,但20AA组血浆氨基酸恢复优于17AA组,创伤处海绵内羟脯氨酸含量20AA组显著高于17AA组(1.29±0.21 vs 0.83±0.16mg/块海绵,P＜0.05).结论创伤后给予富含谷氨酰胺和支链氨基酸的营养制剂能提高血浆氨基酸浓度并有利于创伤的恢复.     

8-羟基鸟嘌呤糖苷酶Ser326Cys基因多态性与男性不育的相关性研究

目的:研究8-羟基鸟嘌呤糖苷酶(OGG1)Ser326Cys位点基因多态性与精液质量及男性不育发病风险的关系。方法:采用病例-对照研究方法,共收集620例原发性不育患者和385例正常生育男性对照,聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法鉴定基因型,精液质量分析采用CASA。结果:携带OGG1 326Cys/Cys(纯和突变型)的个体其精子活动率[(52.1±26.7)%]、精子浓度(3.75±0.91)×106/ml,对数转换值)与携带Ser/Ser野生型的个体[精子活动率(59.0±21.8)%;精子浓度(4.12±0.88)×106/ml,对数转换值]相比显著降低(P0.05);携带OGG1 326 Cys等位基因型的个体与携带Ser/Ser型的个体比较,其患男性不育的风险增加了69%(校正后OR=1.69,95%CI=1.24～2.31)。结论:OGG1 Ser326Cys基因多态性可能是中国南方汉族男性特发性不育的遗传易感因素之一。     

脂连素对大鼠创伤后胰岛素抵抗的作用

目的　观察创伤后胰岛素抵抗现象,探讨脂连素对手术创伤导致的胰岛素抵抗的作用和机制.方法　60只SD大鼠随机分为脂连素组(n=20)、创伤组(n=20)以及对照组(n=20).建立大鼠创伤模型,脂连索组运用脂连素进行预处理(1 mg/kg腹腔内注射),测定大鼠的血糖及血清胰岛素浓度,计算胰岛素抵抗指数(HOMA-IR)和胰岛素分泌指数(HOMA-β);检测骨骼肌胰岛素受体底物蛋白-1( IRS-1)、蛋白激酶B(PKB/Akt)的含量及其磷酸化状态.结果　创伤组与对照组比较血糖浓度明显升高(P＜0.05),血清胰岛素浓度先短暂下降然后逐渐升高(P＜0.05).HOMA-IR明显高于对照组(P＜0.05),HOMA-β则低于对照组(P＜0.05).脂连素组大鼠血糖浓度明显下降(P＜0.05),血清胰岛素浓度无明显改变(P＞0.05).HOMA-IR明显下降(P＜0.05),HOMA-β明显上升(P＜0.05).创伤组与对照组、脂连素组与创伤组大鼠骨骼肌中总的IRS-1及PKB/Akt蛋白含量无明显差异,但创伤组较对照组大鼠骨骼肌的IRS-1酪氨酸(Tyr)位点的磷酸化水平下降了31％[ (88.54±33.48)比(128.60±33.19),F=0.108,P＜0.01],丝氨酸(Ser)位点磷酸化水平增加了64％[(154.31±36.94)比(94.20±27.88),F=0.602,P＜0.01],PKB/Akt的磷酸化水平下降了46％[ (46.58±2.48)比(86.32±3.31),F=0.153,P＜0.01].脂连素组大鼠的骨骼肌IRS-1 Tyr位点的磷酸化水平较创伤组上升了23％[(109.05±30.77)比(88.54±33.48),F=0.012,P＜0.01],而Ser位点磷酸化水平下降了30％ [(118.65±33.49)比(154.31±36.94),F=0.272,P＜0.01],PKB/Akt的磷酸化水平上升了56％[ (72.73±2.95)比(46.58±2.48),F=0.473,P＜0.01].结论 大鼠创伤后存在胰岛素抵抗现象,其机制与胰岛素受体后信号转导通路受阻有关.脂连素能缓解创伤后胰岛素抵抗途径的发生和发展,从而改善创伤后胰岛索抵抗产生的高血糖.     

大鼠严重烫伤早期血浆游离氨基酸浓度的变化

目的 探讨烫伤早期大鼠血浆游离氨基酸含量的变化规律,为研究烧伤后骨骼肌代谢机制异常提供依据。方法 以30％TBSAⅢ度烫伤大鼠为模型,随机分为正常对照组和烧伤后2、6、12和24h共5组,每组8只。用氨基酸自动分析仪的生理体液柱测定血浆游离氨基酸含量,同时测定血清丙氨酸氨基转移酶（ALT）、血清天冬氨酸氨基转移酶（AST）浓度、皮质醇、TNFα和IL－6含量。结果 烫伤后24h内各时相点血浆总氨基酸含量虽然无显性变化,但有不同程度降低趋势;支链氨基酸（BCAA）2h显降低,12h显升高;芳香族氨基酸（AAA）在12和24h显升高;BCAA／AAA比值无显性变化;苯丙氨酸／酪氨酸（Phe/Tyr)比值除伤后2h外,其余各时相点均显升高（P＜0．01）,伤后12h达峰值;血浆TNFα和IL－6含量均显上升（P＜0．01）;IL－6和皮质醇与3－MH和Phe/Tyr呈显正相关。结论 烫伤大鼠因浆氨基酸发生明显变化,其原因可能与早期炎性介质过度释放以及骨骼肌蛋白降解增强和肝功能受损有关,其机制有待进一步研究。     

Effects of high-dose folic acid and pyridoxine on plasma and erythrocyte sulfur amino acids in hemodialysis patients.

In this investigation, sulfur amino acids (sAA) and sulfhydryls were determined in the plasma and erythrocytes (RBC) of 10 uremic patients on regular hemodialysis (HD) treatment and 10 healthy subjects, before and after supplementation with 15 mg/d of folic acid and 200 mg/d of pyridoxine for 4 wk. The basal total plasma concentrations of homocysteine (Hcy), cysteine (Cys), cysteinylglycine (Cys-Gly), gamma-glutamylcysteine (gamma-Glu-Cys), glutathione (GSH), and free cysteinesulfinic acid (CSA) were significantly higher in HD patients when compared to healthy subjects, whereas methionine (Met) and taurine (Tau) concentrations were the same in the two groups. HD patients showed significantly higher RBC levels of Hcy and Cys-Gly, whereas the RBC concentrations of Met, Cys, Tau, and GSH were not different from those in the healthy subjects. The plasma concentrations of sAA and sulfhydryls differed compared with RBC levels in the healthy subjects and HD patients. In both groups, supplementation with high doses of folic acid and pyridoxine reduced the plasma Hcy concentration. In addition, increased plasma concentrations of Cys-Gly and GSH were found in the HD patients and of CSA in the healthy subjects. After vitamin supplementation, the RBC concentrations of Hcy, Cys, and GSH increased and that of Tau decreased in healthy subjects. The only significant finding in RBC of HD patients was an increase in GSH levels after supplementation. This study shows several RBC and plasma sAA and sulfhydryl abnormalities in HD patients, which confirms earlier findings that RBC and plasma pools play independent roles in interorgan amino acid transport and metabolism. Moreover, high-dose supplementation with folic acid and pyridoxine significantly reduced Hcy levels, but did not restore the sAA and sulfhydryl abnormalities to normal levels. The increase that was observed in GSH after vitamin supplementation may have a beneficial effect in improving blood antioxidant status in uremic patients. Finally, the findings of elevated plasma Cys levels correlating to the elevated plasma Hcy levels in the presence of elevated plasma CSA levels, both before and after vitamin supplementation, led to the hypothesis that a block in decarboxylation of CSA is linked to hyperhomocysteinemia in end-stage renal failure.     

Sequential changes in free amino acid pool in burned rabbits]

Free amino acid (FAA) levels in plasma, erythrocytes, bone marrow, skeletal muscle, heart, liver, lung, brain, kidney and spleen were measured simultaneously in rabbits with burn injury. Results of study showed that, 86%-87% of skeletal muscle (remote from burn site), liver and lung FAA, 80%-82% of brain, bone marrow and erythrocyte FAA, 73% of heart, spleen and kidney FAA, and 57% of skeletal muscle (underneath the burn site) FAA varied in levels with the trends similar to that in plasma. These results suggest that the changes in profile of plasma free amino acids may essentially represent that of total amino acid pool after burn injury, and that the plasma amino acid kinetics seems to be a useful index for clinical study.     

Long-term changes in muscle free amino acid levels after elective abdominal surgery.

Characteristic changes in the pattern of muscle free amino acids are seen on the third day after elective surgery. The time course of the restoration to normal levels in uncomplicated cases has not been established before. Seven metabolically healthy patients undergoing cholecystectomy were studied. Muscle biopsy specimens and plasma samples were taken before operation and on days 3, 10, 20 and 30 after surgery. The level of total free amino acids in skeletal muscle decreased and the concentrations of branched chain and aromatic amino acids increased on day 3. The original levels were found to be restored on day 10 after surgery. A decrease in glutamine of 38 per cent (P less than 0.001) was seen on day 3, of 20 per cent (P less than 0.05) on day 10 and of 22 per cent (P less than 0.05) on day 30, compared with preoperative values. These results constitute a baseline for future studies in which the impact of nutritional and pharmacological therapies is to be evaluated beyond the immediate postoperative period.     

Mechanism of amino acid-induced skeletal muscle insulin resistance in humans

Plasma concentrations of amino acids are frequently elevated in insulin-resistant states, and a protein-enriched diet can impair glucose metabolism. This study examined effects of short-term plasma amino acid (AA) elevation on whole-body glucose disposal and cellular insulin action in skeletal muscle. Seven healthy men were studied for 5.5 h during euglycemic (5.5 mmol/l), hyperinsulinemic (430 pmol/l), fasting glucagon (65 ng/l), and growth hormone (0.4 microg/l) somatostatin clamp tests in the presence of low (approximately 1.6 mmol/l) and increased (approximately 4.6 mmol/l) plasma AA concentrations. Glucose turnover was measured with D-[6,6-(2)H(2)]glucose. Intramuscular concentrations of glycogen and glucose-6-phosphate (G6P) were monitored using (13)C and (31)P nuclear magnetic resonance spectroscopy, respectively. A approximately 2.1-fold elevation of plasma AAs reduced whole-body glucose disposal by 25% (P < 0.01). Rates of muscle glycogen synthesis decreased by 64% (180--315 min, 24 plus minus 3; control, 67 plus minus 10 micromol center dot l(-1) center dot min(-1); P < 0.01), which was accompanied by a reduction in G6P starting at 130 min (DeltaG6P(260--300 min), 18 plus minus 19; control, 103 plus minus 33 micromol/l; P < 0.05). In conclusion, plasma amino acid elevation induces skeletal muscle insulin resistance in humans by inhibition of glucose transport/phosphorylation, resulting in marked reduction of glycogen synthesis.     

Water and electrolytes in muscle tissue and free amino acids in muscle and plasma in connection with transurethral resection of the prostate. I. Distilled water as an irrigating fluid.

10 patients undergoing transurethral resection of the prostate using sterile distilled water as an irrigating fluid were studied. The extra- and intracellular distribution of water, the total content of water and electrolytes and the free amino acid concentrations in muscle tissue were determined together with the concentrations of free amino acids in plasma preoperatively, immediately postoperatively and 2 hours postoperatively. The content of water and concentrations of electrolytes in skeletal muscle did not change significantly from the preoperative to the postoperative period with the exception of the potassium concentration, which decreased 2 hours postoperatively. The following free amino acid concentrations in muscle tissue showed significantly decreased values 2 hours postoperatively compared with the preoperative values: taurine, serine, glutamate, proline and leucine. The concentrations of non-essential amino acids in muscle decreased significantly 2 hours postoperatively. This may be interpreted as a dilution effect. An increased concentration of some amino acids in plasma postoperatively may be explained as a haemoconcentration effect due to the use of a postoperative diuretic.     

Acidosis, not azotemia, stimulates branched-chain, amino acid catabolism in uremic rats

To investigate branched-chain, amino acid metabolism (BCAA) in muscle in chronic renal failure (CRF), we studied rats with moderately severe uremia (PUN 110 approximately mg/dl) and spontaneous metabolic acidosis (bicarbonate, 19 +/- 1 mEq/liter). Plasma BCAA levels in CRF compared to pair-fed control rats were approximately 15% lower and muscle valine was 93 microM lower (P less than 0.05). BCAA metabolism was measured in incubated epitrochlearis muscles using L-[1-14C]valine or L-[1-14C]leucine in the presence and absence of insulin. BCAA decarboxylation was increased (P less than 0.05) and insulin-stimulated BCAA incorporation into protein was blunted (P less than 0.05) by CRF. Since we have found that metabolic acidosis, by itself, stimulates muscle branched-chain, ketoacid dehydrogenase activity, another group of CRF and control rats was given NaHCO3 which corrected the acidosis, but not the azotemia. BCAA decarboxylation in muscle was reduced in CRF rats given NaHCO3, and this was reflected in increased plasma and muscle BCAA concentrations. We conclude that in CRF, chronic metabolic acidosis stimulates BCAA decarboxylation in skeletal muscle and this could contribute to the reduced intra- and extracellular concentrations of BCAA. Correction of acidosis should be a goal of therapy in CRF, especially when dietary regimens restrict intake of BCAA.     

Folate, vitamin B12, and sulfur amino acid levels in patients with renal failure

We examined the plasma profile of sulfur amino acids (SAA) in patients with chronic renal failure (CRF) and looked for any correlation with serum folate (FA) and/or vitamin B₁₂. Group 1 comprised 9 patients with CRF and glomerular filtration rate (GFR) >20 ml/min per 1.73 m², 9 patients with GFR<20 ml/min per 1.73 m² comprised group 2, and 14 patients on hemodialysis group 3. The control group comprised 16 healthy children. Homocysteine (Hcy), methionine (Met), cysteine (Cys), and serine (Ser) were measured with gas chromatography. FA and vitamin B₁₂ were measured using enzymatic immunoassay. Median SAA concentrations were significantly lower in controls than in the three groups of patients. Hcy concentrations were 0.8 μmol/l in controls versus 5 μmol/ (group 1), 9 μmol/l (group 2), and 20 μmol/l (group 3). Met concentrations were 26 μmol/l in controls versus 26 μmol/l (group 1), 66 μmol/l (group 2), and 281 μmol/l (group 3). Cys concentrations were 10 μmol/ in controls versus 98 μmol/l (group 1), 54 μmol/l (group 2), and 122 μmol/l (group 3). Ser concentrations were 88 μmol/ in controls versus 153 μmol/l (group 1), 239 μmol/l (group 2), and 240 μmol/l (group 3). The median concentrations of FA were lower in controls than in groups 2 and 3: 5.5 ng/ml versus 8 ng/ml and 15 ng/ml, respectively. Vitamin B₁₂ concentrations did not differ between groups. Vitamin levels did not correlate with SAA. The only difference between patients with Hcy levels in the lower and upper quartile was in Met concentration (38 vs. 263 μmol/l, P<0.02) and GFR (P<0.01). In conclusion, patients with CRF had higher SAA concentrations than healthy children. FA concentrations are higher in CRF patients than in healthy children but did not correlate with concentrations of SAA. Received: 3 January 2000 / Revised: 21 September 2000 / Accepted: 11 October 2000     

Effect of hemodialysis on protein synthesis

BACKGROUND: Earlier studies have shown that hemodialysis (HD) treatment stimulates net protein catabolism. Several factors associated with HD affect protein catabolism, such as an inflammatory effect due to blood-membrane contact and loss of amino acids and glucose into the dialysate. SUBJECTS, MATERIAL AND METHODS: We have studied protein synthesis in skeletal muscle of healthy volunteers (n = 9) before and after a single heparin-free HD. Protein synthesis (PS) was studied, using 2 independent techniques: the incorporation of labeled 2H5-phenylalanine into muscle protein, which gives a quantitative measure of the fractional synthesis rate of muscle proteins, and the concentration and size distribution of ribosomes, which gives a qualitative estimate of protein synthesis. Furthermore, free amino acid concentrations were determined in muscle and plasma. RESULTS: The rate of PS, expressed as the fractional synthesis rate, decreased by 13% during HD (p < 0.02). The capacity for PS, as reflected by the total concentration of ribosomes, was reduced by 22% (p < 0.02) and the activity of PS, expressed as the relative proportion of polyribosomes, decreased from 48.4 +/- 0.9% to 44.8 +/- 0.8% after dialysis (p < 0.01). There was a total loss of 5.8 +/- 0.3 g amino acid to the dialysate. Plasma and muscle free amino acid concentrations were determined at four time points; before and after the phenylalanine incorporation period, before dialysis and before and after the second incorporation period after dialysis. Immediately after dialysis, there was a decrease in plasma asparagine, histidine, alanine, taurine, valine and tryptophane. In muscle, no changes occurred except for a slight increase in leucine after dialysis. In blood, the glucose concentration decreased and the total amount of glucose lost to the dialysate was 21 +/- 3.0 g. In summary, one single hemodialysis treatment decreases fractional protein synthesis rate in skeletal muscle. CONCLUSION: The results demonstrate substantial losses of amino acids and glucose to the dialysate and decreased amino acid concentrations in plasma, but only minimal changes in the intracellular amino acid concentrations in muscle, suggesting that the decreased PS is caused not by lack of amino acid precursors at the site of the synthesis activity, but by other mechanisms.