Ontogeny of carnitine biosynthesis in Sus scrofa domesticus, inferred from γ-butyrobetaine hydroxylase (dioxygenase) activity and substrate inhibition

2020 ◽  
Vol 319 (1) ◽  
pp. R43-R49
Author(s):  
Xi Lin ◽  
Pasha A. Lyvers Peffer ◽  
Jason Woodworth ◽  
Jack Odle

γ-Butyrobetaine hydroxylase (γ-BBH) is the last limiting enzyme of the l-carnitine biosynthesis pathway and plays an important role in catalyzing the hydroxylation of γ-butyrobetaine (γ-BB) to l-carnitine. To study the developmental effect of substrate concentration on the enzyme’s specific activity, kinetics of γ-BBH were measured in liver and kidney from newborn and 1-, 7-, 21-, 35-, 56-, and 210-day-old domestic pigs. Fresh tissue homogenates were assayed under nine concentrations of γ-BB from 0 to 1.5 mM. Substrate inhibition associated with age was observed at ≥0.6 mM of γ-BB. Hepatic activity was low at birth but increased after 1 day. By 21 days, the activity rose by 6.6-fold ( P < 0.05) and remained constant after 56 days. Renal activity was higher than in liver at birth but remained constant through 35 days. By 56 days, the velocity increased by 44% over the activity at birth ( P < 0.05). The apparent Km for γ-BB at birth on average was 2.8-fold higher than at 1 day. The Km value was 60% higher in kidney than liver during development but showed no difference in adult pigs. The total organ enzyme activity increased by 130-fold for liver and 18-fold for kidney as organ weight increased from birth to 56 days. In conclusion, age and substrate affect γ-BBH specific activity and Km for γ-BB in liver and kidney. Whereas the predominant organ for carnitine synthesis is likely the kidney at birth, the liver appears to predominate after the pig exceeds 7 days of age.

1989 ◽  
Vol 62 (1) ◽  
pp. 63-75 ◽  
Author(s):  
Liliane Dupuis ◽  
C. Linda Saunderson ◽  
Antoine Puigserver ◽  
Patrick Brachet

Oxidation of dl-2-hydroxy 4-methylthiobutanoic acid (dl-HMB), dl-methionine (dl-MET) and l-methionine (l-MET) in chicken tissue homogenates was compared using 1-14C-labelled tracers. The pattern of oxidation of the substrates was similar at both low (0.7 mm) and high (20 mm) concentrations. The rate of conversion to 2-keto 4-methylthiobutanoic acid (KMB) was highest for dl-MET and lowest for l-MET in kidney, liver and intestinal mucosa. In breast muscle, rates for dl-MET and l-MET were similar at 0.7 mm, but dl-HMB showed the highest rate at 20 mm. Kidney contained the highest specific activity for oxidation of all three substrates. Raising the pH of liver and kidney homogenates from 7.5 to 8.6 increased the oxidation of dl-MET, exclusively. Experiments with inhibitors of D-2-hydroxy acid dehydrogenase (EC 1.1.99.6) and L-2-hydroxy acid oxidase (EC 1.1.3.15) suggested that d- and l-HMB were stereospecifically oxidized by the enzymes. KMB stimulated l-MET oxidation in kidney yet inhibited l-MET oxidation in liver homogenates. The effect of KMB on dl-MET and dl-HMB oxidation also varied between tissues. Amino-oxyacetate inhibited l-MET oxidation completely and dl-MET and dl-HMB oxidation almost completely in both kidney and liver. L-Cycloserine was less potent than amino-oxyacetate and decreased l-MET oxidation more in kidney than in liver. It can be calculated from the results that, at low substrate concentrations, the liver contributes principally to the whole body oxidation of both dl-HMB and dl-MET. At high (greater than physiological) concentrations, dl-HMB would be oxidized principally in skeletal muscle. At all concentrations, l-MET would be converted to KMB mainly in the muscle.


Animals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 2019
Author(s):  
Salvatore Desantis ◽  
Serena Minervini ◽  
Lorenzo Zallocco ◽  
Bruno Cozzi ◽  
Andrea Pirone

The pig has been increasingly used as a suitable animal model in translational neuroscience. However, several features of the fast-growing, immediately motor-competent cerebral cortex of this species have been adequately described. This study analyzes the cytoarchitecture of the primary motor cortex (M1) of newborn, young and adult pigs (Sus scrofa domesticus). Moreover, we investigated the distribution of the neural cells expressing the calcium-binding proteins (CaBPs) (calretinin, CR; parvalbumin, PV) throughout M1. The primary motor cortex of newborn piglets was characterized by a dense neuronal arrangement that made the discrimination of the cell layers difficult, except for layer one. The absence of a clearly recognizable layer four, typical of the agranular cortex, was noted in young and adult pigs. The morphometric and immunohistochemical analyses revealed age-associated changes characterized by (1) thickness increase and neuronal density (number of cells/mm2 of M1) reduction during the first year of life; (2) morphological changes of CR-immunoreactive neurons in the first months of life; (3) higher density of CR- and PV-immunopositive neurons in newborns when compared to young and adult pigs. Since most of the present findings match with those of the human M1, this study strengthens the growing evidence that the brain of the pig can be used as a potentially valuable translational animal model during growth and development.


Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 2041
Author(s):  
Luiz Jardelino de Lacerda Neto ◽  
Andreza Guedes Barbosa Ramos ◽  
Renata Evaristo Rodrigues da Silva ◽  
Luís Pereira-de-Morais ◽  
Fernanda Maria Silva ◽  
...  

Purpose: Alternative methods for the use of animals in research have gained increasing importance, due to assessments evaluating the real need for their use and the development of legislation that regulates the subject. The principle of the 3R’s (replacement, reduction and refinement) has been an important reference, such that in vitro, ex vivo and cord replacement methods have achieved a prominent place in research. Methods: Therefore, due to successful results from studies developed with these methods, the present study aimed to evaluate the myorelaxant effect of the Dysphania ambrosioides essential oil (EODa) using a Sus scrofa domesticus coronary artery model, and the toxicity of both the Dysphania ambrosioides essential oil and its major constituent, α-terpinene, against Drosophila melanogaster in toxicity and negative geotaxis assays. Results: The EODa relaxed the smooth muscle of swine coronary arteries precontracted with K+ and 5-HT in assays using Sus scrofa domesticus coronary arteries. The toxicity results presented LC50 values of 1.546 mg/mL and 2.282 mg/mL for the EODa and α-terpinene, respectively, thus showing the EODa and α-terpinene presented toxicity to these dipterans, with the EODa being more toxic. Conclusions: Moreover, the results reveal the possibility of using the EODa in vascular disease studies since it promoted the relaxation of the Sus scrofa domesticus coronary smooth muscle.


2021 ◽  
pp. 089875642198909
Author(s):  
Margaret A. Smith ◽  
Sangeeta Rao ◽  
Jennifer E. Rawlinson

Antemortem domestic pig (Sus scrofa domesticus) dental pathology literature is sparse. This observational descriptive study evaluated 23 client-owned pigs that while sedated/anesthetized for routine annual care had intraoral dental radiographs and an oral examination performed. Age, gender, weight, and breed for each pig were recorded. Oral examination and radiographic findings were reviewed to create a comprehensive list of dental abnormalities identified. Descriptive statistics were performed to summarize the data. The study population included 14 castrated males and 20 Vietnamese pot-bellied mini-pigs. The median age was 3 years (range 2-12 years), and the median weight was 39 kg (range 11-140 kg). The most common finding was missing teeth (21/23 pigs); the first premolar tooth was the most likely to be absent (64/106 missing teeth). Periodontal disease was common (20/23 pigs). Advanced stages primarily affected the first molar teeth frequently in the form of a mucogingival defect. Supernumerary roots were discovered on the maxillary canine teeth in female pigs only (10/25 teeth with supernumerary roots). The most common persistent deciduous tooth was the maxillary second incisor (15/19 persistent deciduous teeth). Non-age or gender related open apices were most likely associated with mandibular first and second incisor teeth (26/96 teeth with open apices). Tooth resorption was also identified (7/23 pigs). The study findings prove that pet pigs commonly have dental pathology; therefore, thorough oral examinations with intraoral radiographs should be included in porcine routine health care regimens.


Sign in / Sign up

Export Citation Format

Share Document