Petrus J. Pretorius

The utilization of alanine, glutamic acid, and serine as amino acid substrates for glycine N-acyltransferase

The conjugation of benzoyl‐CoA with the aliphatic and acidic amino acids by glycine N‐acyltransferase, as well as the amides of the latter group, was investigated. Bovine and human liver benzoyl‐amino acid conjugation were investigated using electrospray ionization tandem mass spectrometry (ESI‐MS‐MS). Bovine glycine N‐acyltransferase catalyzed conjugation of benzoyl‐CoA with Gly (KmGly = 6.2 mM), Asn (KmAsn = 129 mM), Gln (KmGln = 353 mM), Ala (KmAla = 1573 mM), Glu (KmGlu = 1148 mM) as well as Ser in a sequential mechanism. In the case of the human form, conjugation with Gly (KmGly = 6.4 mM), Ala (KmAla = 997 mM), and Glu was detected. The presence of these alternative conjugates did not inhibit bovine glycine N‐acyltransferase activity significantly. Considering the relatively low levels at which these conjugates are formed, it is unlikely that they will have a significant contribution to acyl‐amino acid conjugation under normal conditions in vivo. However, their cumulative contribution to acyl‐amino acid conjugation under metabolic disease states may prove to have a useful contribution to detoxification of elevated acyl‐CoAs.

A cysteine for glycine substitution at position 175 in an α1 (i) chain of type I collagen produces a clinically heterogeneous form of osteogenesis imperfecta

The molecular basis for Osteogenesis Imperfecta in a large kindred with a highly variable phenotype was identified by sequencing the mutant pro alpha 1 (I) protein, cDNA and genomic DNA from the proband. Fibroblasts from different affected individuals all synthesize both normal Type I procollagen molecules and abnormal Type I procollagen molecules in which one or both pro alpha 1 (I) chain(s) contain a cysteine residue within the triple helical domain. Protein studies of the proband localized the mutant cysteine residue to the alpha 1 (I) CB 8 peptide. We now report that cysteine has replaced glycine at triple helical residue 175 disrupting the invariant Gly-X-Y structural motif required for perfect triple helix formation. The consequences include post-translational overmodification, decreased thermal stability, and delayed secretion of mutant molecules. The highly variable phenotype in the present kindred cannot be explained solely on the basis of the cysteine for glycine substitution but will require further exploration.

The influence of acculturation on endocrine reactivity during acute stress in urban black males

Urbanization is a world-wide phenomenon and results in a radical and sometimes total change in living conditions. This process is accompanied by a significant increase in the incidence of western-type diseases virtually unknown in traditional rural communities. Especially in a multicultural society like South Africa, rural people moving to the city will experience cultural shock leading in many cases to a large degree of acculturation. In this study the effect of acculturation on endocrine reactivity was studied in a population of Tswanas. It was found that significant differences in endocrine reactivity exist not only between rural Tswanas and urban whites but in some instances also between rural Tswanas and urban Tswanas. During the cold pressor test, the testosterone reactivity and to a lesser extent the prolactin reactivity of the urban Tswanas tended to approach that of the white group as a function of their level of acculturation. All the Tswana groups had a significantly higher plasma renin activity during acute stress than the whites, which could have a bearing on the tendency of urban blacks to develop hypertension.

Cardiovascular reactivity patterns elicited by the cold pressor test as a function of aging

Background and aims: The cold pressor test has been widely used in previous cardiovascular reactivity studies as a predictor of hypertension. However, the influence of the physical adaptations of the arterial wall with increasing age on reactivity has not been delineated. Methods: 64 men divided into 5 different age groups participated in a laboratory protocol consisting of submerging one hand in ice water for one minute while changes in blood pressure were continuously measured. Results: The results indicated that with increasing age, the systolic blood pressure change, especially the rate of change (slope) is more pronounced than changes in diastolic blood pressure. Conclusions: With increasing age, there is a shift from a diastolic blood pressure reactivity pattern to a more systolic blood pressure reactivity pattern during application of the cold pressor test. This could be ascribed to a decrease in arterial compliance.