Enzymology of the branched-chain amino acid oxidation disorders: the valine pathway

Valine is one of the three branched-chain amino acids which undergoes oxidation within mitochondria. In this paper, we describe the current state of knowledge with respect to the enzymology of the valine oxidation pathway and the different disorders affecting oxidation

Is increased time to diagnosis and treatment in symptomatic cancer associated with poorer outcomes?:Systematic review

background: It is unclear whether more timely cancer diagnosis brings favourable outcomes, with much of the previous evidence, in some cancers, being equivocal. We set out to determine whether there is an association between time to diagnosis, treatment and clinical outcomes, across all cancers for symptomatic presentations. methods: Systematic review of the literature and narrative synthesis. results: We included 177 articles reporting 209 studies. These studies varied in study design, the time intervals assessed and the outcomes reported. Study quality was variable, with a small number of higher-quality studies. Heterogeneity precluded definitive findings. The cancers with more reports of an association between shorter times to diagnosis and more favourable outcomes were breast, colorectal, head and neck, testicular and melanoma. conclusions: This is the first review encompassing many cancer types, and we have demonstrated those cancers in which more evidence of an association between shorter times to diagnosis and more favourable outcomes exists, and where it is lacking. We believe that it is reasonable to assume that efforts to expedite the diagnosis of symptomatic cancer are likely to have benefits for patients in terms of improved survival, earlier-stage diagnosis and improved quality of life, although these benefits vary between cancers

Cloning, Expression and Characterization of 3-Hydroxyisobutyrate Dehydrogenase from Pseudomonas denitrificans ATCC 13867

The gene encoding an NAD+-dependent, 3-hydroxyisobutyrate dehydrogenase (3HIBDH-IV) from Pseudomonas denitrificans ATCC 13867 was cloned and expressed in Escherichia coli BL 21 (DE3) and characterized to understand its physiological relevance in the degradation of 3-hydroxypropionic acid (3-HP). The deduced amino acid sequence showed high similarity to other 3-hydroxyisobutyrate dehydrogenase isozymes (3HIBDHs) of P. denitrificans ATCC 13867. A comparison of 3HIBDH-IV with its relevant enzymes along with molecular docking studies suggested that Lys171, Asn175 and Gly123 are important for its catalytic function on 3-hydroxyacids. The recombinant 3HIBDH-IV was purified to homogeneity utilizing a Ni-NTA-HP resin column in high yield. 3HIBDH-IV was very specific to (S)-3-hydroxyisobutyrate, but also catalyzed the oxidation of 3-HP to malonate semialdehyde. The specific activity and half-saturation constant (K-m) for 3-HP at 30 degrees C and pH 9.0 were determined to be 17 U/mg protein and 1.0 mM, respectively. Heavy metals, such as Ag+ and Hg2+, completely inhibited the 3HIBDH-IV activity, whereas dithiothreitol, 2-mercaptoethanol and ethylenediaminetetraacetic acid increased its activity 1.5-1.8-fold. This paper reports the characteristics of 3HIBDH-IV as well as its probable role in 3-HP degradatio