BioChem, Volume 2, Issue 3 (September 2022) – 3 articles

The incidence of male infertility has been increasing over the years and is now becoming a serious health problem. This trend has been followed by an increase in metabolic diseases, which are known to induce clear alterations in testicular metabolism, although the underlying mechanismremain unclear. Testicular metabolism displays several unique features, with testicular somatic cells being central in providing the conditions needed for spermatogenesis, including its nutritional and hormonal support. In addition to glucose and lactate, the two main energy sources used by the testis, glycogen is also present in testicular cells. Glycogen metabolism is a potential source of glucose to both testicular somatic (namely Sertoli and Leydig cells) and germ cells. Many of the enzymes involved in the pathways of the synthesis and degradation of glycogen were identified in these cells, emphasising the relevance of this complex carbohydrate. Glycogen, however, has other non-canonical functions in testicular cells; besides its role as a source of energy, it is also associated with events such as cellular differentiation and apoptosis. In this review, we address the relevance of testicular glycogen metabolism, focusing on its role in Sertoli and Leydig cells and spermatogenesis. In addition, all the available information on the role of glycogen and related pathways in male infertility cases is discussed. Our discussion highlights that glycogen metabolism has been somewhat overlooked in testis and its contribution to spermatogenesis may be underestimated. Full article

Metalloenzymes are the most proficient nature catalysts that are responsible for diverse biochemical transformations introducing excellent selectivity and performing at high rates, using intricate mutual relationships between metal ions and proteins. Inspired by nature, chemists started using naturally occurring proteins as templates to harbor non-native metal catalysts for the sustainable synthesis of molecules for pharmaceutical, biotechnological and industrial purposes. Therefore, metalloenzymes are the relevant targets for the design of artificial biocatalysts. The search and development of new scaffolds capable of hosting metals with high levels of selectivity could significantly expand the scope of bio-catalysis. To meet this challenge, herein, three native scaffolds: [1Fe-4Cys] (rubredoxin), [3Fe-4S] (ferredoxin), and [S₂MoS₂CuS₂MoS₂]-ORP (orange protein) protein scaffolds are case studies describing templates for the synthesis of non-native monomeric to mixed metal–sulfur clusters, which mimic native Ni containing metalloenzymes including [Ni-Fe] Hydrogenase and [Ni-Fe] CO Dehydrogenase. The non-native metal-substituted metalloproteins are not only useful for catalysis but also as spectroscopic probes. Full article

Three forms of methylated cytosines are present in the eukaryotic genome: 3-methylcytosine, 4-methylcytosine and 5-methylcytosine. 3-methylcytosines create methyl lesions, which impair local DNA function and flexibility, resulting in replication and transcription error. On the other hand, 5-methylcytosine is usually present at the gene promoter which blocks transcription and translation. Fe(II)/2OG-dependent nucleic acid-modifying enzymes are the class of enzymes responsible for the demethylation of these modified cytosines. ALKBH2 and 3 remove 3-methylcytosine via a one-step direct demethylation process. On the other hand, active demethylation of 5mC is initiated by Ten-Eleven Translocation (TET)-family dioxygenases. Via oxidative demethylation, TET1-3 converts 5mC into 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine. Remarkably, recent findings demonstrate that ALKBH2,3 possess oxidative demethylation properties, along with direct demethylation. On the other hand, the TET family of enzymes possess direct demethylation properties along with oxidative demethylation. Here we review the importance of methylated cytosines in human DNA, their origin, function and removal. In addition, we discuss the recent findings of extraordinary flexibility of Fe(II)/2OG-dependent nucleic acid-modifying enzymes ALKBH2,3 and TET family of enzymes in cytosine demethylation, as well as their impact on epigenetics. Full article