Thesis (Ph.D.)--Ohio University, November, 2008. / Title from PDF t.p. Release of full electronic text on OhioLINK has been delayed until December 1, 2012. Includes bibliographical references (leaves 145-153)

Thesis (Ph.D.)--Ohio University, November, 2008. / Release of full electronic text on OhioLINK has been delayed until December 1, 2012. Includes bibliographical references (leaves 145-153)

Thesis (doctoral)--Mälmo, 1982.

Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (p. 154-168).

The studies presented in this dissertation establish the dynamics of Eleven nineteen Lysine-rich leukemia (ELL) family of elongation factors during B cell differentiation and provide a description of ELL3 function in B cells. The transition from a mature naïve B cells into an activated B cell is dependent on a large increase in transcriptional output, which is followed by focused expression on secreted immunoglobulin upon terminal differentiation into plasma cell. While ELL family members have previously been implicated in alternative splicing at the immunoglobulin heavy chain locus in plasma cells, their presence and function prior to differentiation is currently not known. However, the use of elongation factors has been implied by the finding of mostly paused RNA polymerase II in the genome of naïve B cells. In the first study, the expression of transcriptional elongation factor ELL3 is shown to be restricted to activated B cells and B cell lymphomas. All three family members were characterized in B cell lymphoma cell lines, genome wide expression, microarray analysis and primary B cell stimulus. The expression of ELL3 was induced upon activation of B cells concurrently with family member ELL. In addition, the abundant expression of ELL3 was restricted to GC derived B cell lymphoma cell lines. While the expression of ELL is maintained, the expression of ELL3 is diminished and ELL2 is up-regulated in terminally differentiated plasma cells. The expression of master regulator of terminal plasma cell differentiation PRDM1 was inverse correlated with that of ELL3. To further establish PRDM1s role in regulating the ELL family member dynamics, global binding was assessed in plasma cell lines. Chromatin immunoprecipitation followed by quantitative PCR was utilized to identify direct association of PRDM1 at exclusively the ELL3 loci. Ectopic expression of PRDM1 in B cells down regulated the expression of ELL3. Furthermore, two consensus PRDM1 binding sites were defined at the ELL3 loci, which mediate significant repression of the promoter activity. Collectively, these experiments indicate that PRDM1 mediates the switch from ELL3 in B cells to ELL2 in plasma cells. The data presented in the final chapter aimed at defining a function for ELL3 in the cells that express it most abundantly, which are B cell lymphoma cell lines. Transient depletion of ELL3 in a Burkitt’s lymphoma cell line resulted in a diminished proliferation rate due to a severe disruption of DNA replication and its regulators minichromosome maintenance proteins. Additionally, compromised cell division and mitotic regulators were observed along with increased DNA damage and cell death. The data presented here demonstrate a key role for ELL3 in the proliferation and survival of B cell lymphomas and positions ELL3 as an attractive therapeutic target against B cell lymphoma’s with a germinal center origin.

O objetivo desta dissertação foi estimar a exigência de lisina (Lis) para frangos de corte machos Cobb x Cobb 500 de 1 a 12 dias de idade (experimento 1), 12 a 28 dias de idade (experimento 2) e 28 a 42 dias de idade (experimento 3). Dietas basais foram formuladas para atingir ou exceder as exigências nutricionais, com exceção da Lis. Cinco níveis de Lis foram suplementados às dietas basais a partir de L-Lis HCl ou sulfato de L-Lis de modo que os níveis variaram de 0,97% a 1,37% de Lis digestível no experimento 1, 0,77% a 1,17% de Lis digestível no experimento 2 e 0,68% a 1,08% de Lis digestível no experimento 3 em incrementos de 0,08%. Os tratamentos foram distribuídos em um delineamento inteiramente casualizado com 8 repetições de 25 aves. Em cada experimento, 2200 aves foram alojadas em 88 unidades experimentais. Nos dias 1 e 12 (experimento 1), 12 e 28 (experimento 2) e 28 e 42 (experimento 3) as aves e a ração foram pesadas para determinar o ganho de peso (GP) e conversão alimentar (CA). No experimento 3, quatro aves por unidade experimental foram abatidas para determinação do rendimento de carcaça e peito. A biodisponibilidade relativa (RBV) das fontes de Lis foi avaliada através de uma regressão multivariada e comparada pelo teste t. A exigência de Lis foi estimada por três modelos de regressão: polinomial quadrática, brokenline linear e broken-line quadrática. A exigência foi representada como 95% do ponto de máxima resposta. Não houve diferença entre a RBV da Lis no sulfato de L-Lis em relação ao L-Lis HCl, portanto ambas as fontes foram utilizadas para estimar as exigências. As exigências encontradas variaram de acordo com o modelo estatístico e a variável analisada. A regressão broken-line quadrática apresentou o melhor ajustamento aos dados de desempenho, enquanto a regressão broken-line linear se ajustou melhor aos dados de rendimento de carcaça e peito. As regressões polinomial quadrática, broken-line linear e broken-line quadrática estimaram, respectivamente, as exigências como 1,190, 1,032 e 1,101% para GP e 1,226, 1,038 e 1,124% para CA no experimento 1; 1,021, 0,900 e 0,961% para GP e 1,064, 0,966 e 1,043% para CA no experimento 2; 0,949, 0,833 e 0,925% para GP, 0,978, 0,851 e 0,960% para CA, 0,933, 0,842 e 0,931% para rendimento de carcaça e 0,952, 0,839 e 0,921% para rendimento de peito no experimento 3. Os resultados demonstraram que as exigências de Lis foram consideravelmente influenciadas pelas diferentes regressões. Portanto, a escolha do modelo estatístico é crítica para a obtenção de estimativas precisas e coerentes. / The objective of this thesis was to estimate lysine (Lys) requirement of male Cobb x Cobb 500 broilers from 1 to 12 days of age (experiment 1), 12 to 28 days of age (experiment 2), and 28 to 42 days of age (experiment 3). Basal diets were formulated to meet or exceed recommendations, except for Lys. Five graded levels of Lys were supplemented from L-Lys HCl or L-Lys sulfate to the basal diets. Dietary treatments ranged from 0.97% to 1.37% digestible Lys in experiment 1, 0.77% to 1.17% digestible Lys in experiment 2, and 0.68% to 1.08% digestible Lys in experiment 3 in 0.08% increments. Treatments were distributed in a completely randomized design with 8 repetitions of 25 birds each. A total of 2,200 birds per experiment were placed in 88 experimental units. At 1 and 12 days (experiment 1), 12 and 28 days (experiment 2), and 28 and 42 days (experiment 3), birds and feed were weighed to determine body weight gain (BWG) and feed conversion ratio (FCR). In experiment 3, four birds per experimental unit were processed for carcass and breast meat yield evaluation. Relative bioavailability (RBV) of Lys sources was assessed by a multivariate regression and compared by a t-test. Lysine requirement was estimated using three regression models: quadratic polynomial, linear broken-line, and quadratic broken-line. Requirements were represented as 95% of the asymptote. No difference was observed in Lys RBV in L-Lys sulfate compared to L-Lys HCl, thus both sources were used to estimate requirements. Requirement estimates varied according to statistic model and analyzed variable. Quadratic broken-line model presented the best fit to performance data (BWG and FCR), whereas linear broken-line model fitted better to carcass and breast meat yield data. Quadratic polynomial, linear broken-line, and quadratic brokenline estimates were, respectively, 1.190, 1.032, and 1.101% for BW gain and 1.226, 1.038, and 1.124% for FCR in experiment 1; 1.021, 0.900, and 0.961% for BW gain and as 1.064, 0.966, and 1.043% for FCR in experiment 2; and 0.949, 0.833, 0.925% for BW gain, 0.978, 0.851, and 0.960% for FCR, 0.933, 0.842, and 0.931% for carcass yield, and 0.952, 0.839, and 0.921% for breast meat yield in experiment 3. Results demonstrate that Lys requirements were considerably influenced by different regression models. Therefore, the choice of statistical model is crucial to obtain precise, coherent estimates.

Master of Science / Animal Sciences and Industry / Evan C. Titgemeyer / Six ruminally-cannulated Holstein steers (202 ± 15 kg) were used to study the effects of ruminal ammonia loading on whole-body lysine utilization. Steers were housed in metabolism crates and used in a 6 × 6 Latin square design. All steers received 2.52 kg of DM/d of a diet (10.1% CP) containing 82% soybean hulls, 8% wheat straw, 5% cane molasses, and 5% vitamins and minerals. Ten g/d of urea was infused continuously into the rumen of all steers to ensure adequate ruminal ammonia concentrations; concurrently, steers were ruminally infused continuously with 200 g/d acetic acid, 200 g/d propionic acid, and 50 g/d of butyric acid and abomasally infused with 300 g/d of glucose continuously to increase energy supply without increasing microbial protein supply. Steers were also abomasally infused continuously with an excess of all essential amino acids except lysine to ensure that lysine was the only limiting amino acid. Treatments were arranged as a 3 × 2 factorial with 3 additional levels of urea (0, 40, or 80 g/d) continuously infused ruminally to induce ammonia loading and 2 levels of lysine (0 or 6 g/d) continuously infused abomasally. Treatments did not affect fecal N output (P = 0.37). Lysine supplementation decreased (P < 0.01) urinary N excretion from 51.9 g/d to 44.3 g/d, increased (P < 0.01) retained N from 24.4 to 33.3 g/d, and tended (P = 0.09) to reduce plasma urea-N. Urea infusions linearly increased retained N (26.7, 28.8, and 31.1 g/d; P = 0.05) and also linearly increased (P < 0.01) urinary N excretion (31.8, 48.1, and 64.4 g/d), urinary urea (21.9, 37.7, and 54.3 g/d), urinary ammonia (1.1, 1.4, and 1.9 g/d), and plasma urea (2.7, 4.0, and 5.1 mM) for 0, 40, and 80 g urea/d, respectively. Assuming that retained protein is 6.25 × retained N and contains 6.4% lysine, the incremental efficiencies of infused lysine utilization were 51, 59, and 69% for steers receiving 0, 40, and 80 g/d of urea, respectively, suggesting that the ruminal ammonia loads might improve the efficiency of lysine utilization; this is supported by the observed increases in whole-body protein deposition in response to ammonia loading of our steers that were, by design, lysine deficient.

O objetivo desta dissertação foi estimar a exigência de lisina (Lis) para frangos de corte machos Cobb x Cobb 500 de 1 a 12 dias de idade (experimento 1), 12 a 28 dias de idade (experimento 2) e 28 a 42 dias de idade (experimento 3). Dietas basais foram formuladas para atingir ou exceder as exigências nutricionais, com exceção da Lis. Cinco níveis de Lis foram suplementados às dietas basais a partir de L-Lis HCl ou sulfato de L-Lis de modo que os níveis variaram de 0,97% a 1,37% de Lis digestível no experimento 1, 0,77% a 1,17% de Lis digestível no experimento 2 e 0,68% a 1,08% de Lis digestível no experimento 3 em incrementos de 0,08%. Os tratamentos foram distribuídos em um delineamento inteiramente casualizado com 8 repetições de 25 aves. Em cada experimento, 2200 aves foram alojadas em 88 unidades experimentais. Nos dias 1 e 12 (experimento 1), 12 e 28 (experimento 2) e 28 e 42 (experimento 3) as aves e a ração foram pesadas para determinar o ganho de peso (GP) e conversão alimentar (CA). No experimento 3, quatro aves por unidade experimental foram abatidas para determinação do rendimento de carcaça e peito. A biodisponibilidade relativa (RBV) das fontes de Lis foi avaliada através de uma regressão multivariada e comparada pelo teste t. A exigência de Lis foi estimada por três modelos de regressão: polinomial quadrática, brokenline linear e broken-line quadrática. A exigência foi representada como 95% do ponto de máxima resposta. Não houve diferença entre a RBV da Lis no sulfato de L-Lis em relação ao L-Lis HCl, portanto ambas as fontes foram utilizadas para estimar as exigências. As exigências encontradas variaram de acordo com o modelo estatístico e a variável analisada. A regressão broken-line quadrática apresentou o melhor ajustamento aos dados de desempenho, enquanto a regressão broken-line linear se ajustou melhor aos dados de rendimento de carcaça e peito. As regressões polinomial quadrática, broken-line linear e broken-line quadrática estimaram, respectivamente, as exigências como 1,190, 1,032 e 1,101% para GP e 1,226, 1,038 e 1,124% para CA no experimento 1; 1,021, 0,900 e 0,961% para GP e 1,064, 0,966 e 1,043% para CA no experimento 2; 0,949, 0,833 e 0,925% para GP, 0,978, 0,851 e 0,960% para CA, 0,933, 0,842 e 0,931% para rendimento de carcaça e 0,952, 0,839 e 0,921% para rendimento de peito no experimento 3. Os resultados demonstraram que as exigências de Lis foram consideravelmente influenciadas pelas diferentes regressões. Portanto, a escolha do modelo estatístico é crítica para a obtenção de estimativas precisas e coerentes. / The objective of this thesis was to estimate lysine (Lys) requirement of male Cobb x Cobb 500 broilers from 1 to 12 days of age (experiment 1), 12 to 28 days of age (experiment 2), and 28 to 42 days of age (experiment 3). Basal diets were formulated to meet or exceed recommendations, except for Lys. Five graded levels of Lys were supplemented from L-Lys HCl or L-Lys sulfate to the basal diets. Dietary treatments ranged from 0.97% to 1.37% digestible Lys in experiment 1, 0.77% to 1.17% digestible Lys in experiment 2, and 0.68% to 1.08% digestible Lys in experiment 3 in 0.08% increments. Treatments were distributed in a completely randomized design with 8 repetitions of 25 birds each. A total of 2,200 birds per experiment were placed in 88 experimental units. At 1 and 12 days (experiment 1), 12 and 28 days (experiment 2), and 28 and 42 days (experiment 3), birds and feed were weighed to determine body weight gain (BWG) and feed conversion ratio (FCR). In experiment 3, four birds per experimental unit were processed for carcass and breast meat yield evaluation. Relative bioavailability (RBV) of Lys sources was assessed by a multivariate regression and compared by a t-test. Lysine requirement was estimated using three regression models: quadratic polynomial, linear broken-line, and quadratic broken-line. Requirements were represented as 95% of the asymptote. No difference was observed in Lys RBV in L-Lys sulfate compared to L-Lys HCl, thus both sources were used to estimate requirements. Requirement estimates varied according to statistic model and analyzed variable. Quadratic broken-line model presented the best fit to performance data (BWG and FCR), whereas linear broken-line model fitted better to carcass and breast meat yield data. Quadratic polynomial, linear broken-line, and quadratic brokenline estimates were, respectively, 1.190, 1.032, and 1.101% for BW gain and 1.226, 1.038, and 1.124% for FCR in experiment 1; 1.021, 0.900, and 0.961% for BW gain and as 1.064, 0.966, and 1.043% for FCR in experiment 2; and 0.949, 0.833, 0.925% for BW gain, 0.978, 0.851, and 0.960% for FCR, 0.933, 0.842, and 0.931% for carcass yield, and 0.952, 0.839, and 0.921% for breast meat yield in experiment 3. Results demonstrate that Lys requirements were considerably influenced by different regression models. Therefore, the choice of statistical model is crucial to obtain precise, coherent estimates.

Introdução: existe evidencia de que o sabor umami detecta os alimentos ricos em proteínas e aminoácidos, o que presumivelmente interfere na ingestão destes alimentos. Há experimentos publicados que relacionam quadros de desnutrição ou alimentação deficiente de determinados aminoácidos, com o consumo voluntário de soluções ou ração contendo tais aminoácidos. Objetivos: os objetivos deste trabalho foram: a caracterização das preferências gustativas para diferentes aminoácidos no rato normal e o efeito da desnutrição protéica sobre essas preferências. Metodologia: o estudo compreendeu duas fases distintas: na primeira foram feitas comparações de consumo de soluções de aminoácidos isolados (10 gramas por litro de água) em um período curto (5 dias). As comparações foram realizadas em 4 grupos distintos, e cada grupo foi composto de 20 animais: 10 controles e 10 desnutridos. A desnutrição foi induzida pelo oferecimento de ração hipoprotéica (5% de caseína na primeira fase e 7,5% de caseína na segunda fase). As soluções de aminoácidos comparadas em cada grupo foram: glutamato e glicina, glutamato e valina, triptofano e glicina e triptofano e valina, todas na concentração de 10g/ L. Na segunda fase foram realizadas comparações de consumo de soluções contendo glutamato mais um aminoácido não essencial (glicina) e glutamato mais um aminoácido essencial (lisina ou triptofano) por um período de 42 dias. Esta segunda fase foi composta de 3 grupos de animais, sendo um formado por 10 animais controles e 10 desnutridos que não receberam soluções, outro grupo com a mesma divisão de animais, mas que receberam soluções de glutamato mais glicina e glutamato mais lisina, e o último grupo recebeu soluções de glutamato mais glicina e glutamato mais triptofano. Resultados, discussão e conclusão: observou-se, tanto na fase 1 como na fase 2, que: a glicina e o glutamato em solução são muito atrativos; a de lisina é atrativa 4 mas em menor intensidade do que as anteriores; a de valina é pouco atraente; o consumo da solução de triptofano foi tão pequena que esta é possivelmente aversiva. Os resultados da fase 1 indicaram que o consumo de soluções de glutamato e de valina de animais desnutridos foi significativamente maior do que o de animais controles. Entretanto, no subgrupo de ratos desnutridos, o consumo da solução de glutamato correlacionou-se positivamente com o peso do animal. Na fase 2 os animais desnutridos, nas duas últimas semanas experimentais, mas não nas anteriores, apresentaram consumo significativamente maior de lisina e triptofano; a comparação do consumo de solução de glicina foi impossibilitada pelo consumo excessivo e esgotamento dos frascos. Também se constatou que os animais da segunda fase apresentaram esteatose hepática. Entre os desnutridos, o consumo de solução de lisina foi inversamente correlacionado com o peso corporal / Umami is the taste quality associated with several amino acids, especially the amino acid L-glutamate, and evidence exists that umami indicates the presence of amino acids, peptides and related structures in foodstuffs, which may bear relevant nutritional implications. The objectives of the study were to establish the normal rat preferences among a set of amino acids (glycine, glutamate, lysine, valine and tryptophan), and determine wether the rat protein malnutrition modifies the preferences and/or the avidity for these amino acids. In a initial set of experiments, bottles containing 50 ml of the amino acid solutions whose palatability were to be compared were presented to each animal for a 5-day period, and volumes consumed during the last 3 days were measured, and the bottles were refilled to their original levels. The left-right positions of the bottles were reversed every day. At the termination of the testing periods, the volumes of test solutions remaining in each bottle were measured, and the consumed volumes calculated. In a second set of experiments, solutions of glutamate plus glycine, glutamate plus lysine or glutamate plus tryptophan were presented to the animals for 8 weeks; after that , for 2 weeks, the glutamate was removed so that solutions of glycine, lysine or tryptophan only were presented to the animals. The volumes remaining in the bottles were measured and the volumes consumed calculated at termination of each testing period. On the basis of the ratios of volume of solutions consumed/ body weight the avidity for the amino acid were inferred. Protein malnutrition was induced by a diet with 5% -7.5 % casein as the only protein source; malnutrition was consistently induced as demonstrated by severe reduction in weight gain and increase in liver fat content. Normal rats demonstrated great avidities for glycine and glutamate, moderate avidity for lysine, low avidity for valine and no avidity for tryptophan. Rats with protein malnutrition a similar profile of avidities, however they significantly grater avidities for 6 glutamate, lysine, valine, and tryptophan, but not for glycine than normal rats. Among the rats with with protein malnutrition, greater the body weight, the greater the glutamate solution comsumed/body weight and the lower the body weight, the greater the lysine solution consumed /body weight. Conclusions: Avidity for amino acid solutions is widely variable, and protein malnutrition enhances the avidity for glutamate, valine, lysine, and tryptophan solutions but not for glycine solution

A lisina é um dos aminoácidos essenciais e um dos fatores limitantes ao uso de cereais como o milho na alimentação, pois, sem suplementação, não permite a obtenção de uma dieta balanceada. A fim de melhorar a qualidade nutricional dos cereais, várias tentativas têm sido realizadas baseadas em resultados obtidos sobre as rotas de metabolismo da lisina em plantas e o acúmulo de proteínas de reserva no endosperma. Ambrozevicius (2010) com o objetivo de produzir plantas de milho transgênicas com alto teor de lisina utilizou a estratégia de expressão de proteínas de reserva de outras espécies vegetais ricas em lisina, ou seja, através da expressão de uma proteína heteróloga: a zeolina. O presente trabalho teve como objetivo estudar os 6 eventos transformados expressando a zeolina na geração F3, caracterizando as proteínas de reserva, o perfil de aminoácidos e as enzimas envolvidas no metabolismo de lisina em milho geneticamente modificado, para compreender quais as possíveis alterações bioquímicas podem ter sido geradas pela transformação, e que podem ter levado ao incremento dos aminoácidos essenciais neste material transgênico. O perfil de proteínas de reserva dos eventos transformados exibiu redução na proporção das zeínas II e glutelinas em relação ao controle HiII, e ainda aumentos muito discretos da fração globulina, porém não para todos os eventos transformados. Na composição de aminoácidos solúveis totais foram observados incrementos nos teores dos aminoácidos que fazem parte da via metabólica do ácido aspártico: lisina, metionina, treonina e isoleucina. Para os aminoácidos incorporados em proteínas, foram observados incrementos nos teores de lisina nos eventos transformados da fração globulina e da fração glutelina, ambos em relação ao controle HiII. Já a fração zeína I teve o maior conteúdo total de aminoácidos em todos os eventos transformados. A análise das enzimas envolvidas no metabolismo de lisina revelou que ocorreram alterações em duas enzimas, a primeira enzima envolvida na síntese de lisina, aspartato quinase (AK) e a segunda envolvida na degradação de lisina, lisina cetoglutarato redutase (LOR). Embora as outras enzimas envolvidas na síntese e na degradação de lisina também tenham sido alteradas, os resultados foram variáveis para os diferentes eventos. Este trabalho mostrou que a expressão da proteína heteróloga zeolina causou alterações na composição das frações protéicas, no teor dos aminoácidos solúveis totais e aminoácidos incorporados em proteína em consequencia das alterações das enzimas envolvidas na síntese e degradação da lisina. Os resultados obtidos sugerem que a expressão da proteína heteróloga zeolina, que tem a necessidade de incorporação de lisina em sua estrutura, pode ter alterado a via metabólica do ácido aspártico para suprir a nova demanda de lisina. Essas alterações podem incluir o aumento na atividade da enzima AK, que é a primeira enzima da via que leva a síntese deste aminoácido e também uma redução na atividade da enzima de degradação LOR, pois o excesso de lisina livre que seria degradada é incorporado à nova proteína. / Lysine is an essential amino acid and one of the limiting factors for the use in cereals such as corn feed therefore, without supplementation; it does not allow obtaining a balanced diet. In order to improve the nutritional quality of cereals, several attempts have been made based on the results about routes of metabolism of lysine in plants and accumulation of storage proteins in endosperm. Ambrozevicius (2010) with the objective of producing transgenic corn plants with high content of lysine used a strategy of expression of storage proteins from other plant species which are rich in lysine, it means, through the expression of a heterologous protein: zeolin. This work aimed to study the 6 events processed expressing zeolina in F3 generation, featuring the storage proteins, the profile of amino acids and enzymes involved in the metabolism of lysine in genetically modified corn, in order to understand the possible biochemical changes which may have been generated by the transformation, and that may have led to the increase of essential amino acids in transgenic material The storage protein profile of transformed events exhibited reduction in the proportion of zein II and glutelins compared to control HiII, and yet very discrete increments of globulin, but not for all events processed. In the composition of soluble amino acids, it was observed increments in concentration of amino acids forming part of the metabolic pathway of aspartic acid: Lysine, methionine, threonine and isoleucine. For the amino acids incorporated into proteins, it was observed increments in the levels of lysine in the transformed events of globulin and glutelin fraction, both in relation to the control HiII. On the other hand, zein fraction I had the highest total amino acid content in all transformed events. The analysis of the enzymes involved in the metabolism of lysine revealed that changes occurred in two enzymes, the first enzyme involved in the synthesis of lysine, aspartate kinase (AK) and the second involved in the degradation of lysine, lysine ketoglutarate reductase (LOR). Although other enzymes involved in the synthesis and degradation of lysine have also been changed, the results were variable for different events. This work showed that the expression of heterologous protein zeolina caused changes in the composition of protein fractions, in the content of soluble amino acids and amino acids incorporated in consequence of changes in enzymes involved in the synthesis and degradation of lysine. The results suggest that the expression of heterologous protein zeolina, which has the need for incorporation of lysine in its structure, may have changed the aspartic acid pathway to meet the new demand for lysine. These changes may include the increase in AK enzyme activity, which is the first enzyme of the pathway leading to the synthesis of this amino acid and also a reduction in the activity of the enzyme degradation LOR, since the excess free lysine would be degraded is incorporated into the new protein.