Succinic acid is a dicarboxylic acid with the chemical formula (CH2)2(CO2H)2. The name derives from Latin succinum, meaning amber. In living organisms, succinic acid takes the form of an anion, succinate, which has multiple biological roles as a metabolic intermediate being converted into fumarate by the enzyme succinate dehydrogenase in complex 2 of the electron transport chain which is involved in making ATP, and as a signaling molecule reflecting the cellular metabolic state. It is marketed as food additive E363. Succinate is generated in mitochondria via the tricarboxylic acid cycle (TCA), an energy-yielding process shared by all organisms. Succinate can exit the mitochondrial matrix and function in the cytoplasm as well as the extracellular space, changing gene expression patterns, modulating epigenetic landscape or demonstrating hormone-like signaling. As such, succinate links cellular metabolism, especially ATP formation, to the regulation of cellular function. Dysregulation of succinate synthesis, and therefore ATP synthesis, happens in some genetic mitochondrial diseases, such as Leigh syndrome, and Melas syndrome, and degradation can lead to pathological conditions, such as malignant transformation, inflammation and tissue injury.
Cerebral hypoxia is a form of hypoxia, specifically involving the brain; when the brain is completely deprived of oxygen, it is called cerebral anoxia. There are four categories of cerebral hypoxia; they are, in order of severity: diffuse cerebral hypoxia (DCH), focal cerebral ischemia, cerebral infarction, and global cerebral ischemia. Prolonged hypoxia induces neuronal cell death via apoptosis, resulting in a hypoxic brain injury.
Hypoxia-inducible factors (HIFs) are transcription factors that respond to decreases in available oxygen in the cellular environment, or hypoxia.
The HIF-1α internal ribosome entry site (IRES) is an RNA element present in the 5' UTR of the mRNA of HIF-1α that allows cap-independent translation. The HIF-1α internal ribosome entry site (IRES) allows translation to be maintained under hypoxic cell conditions that inhibit cap-dependent translation [1]. The hypoxia-inducible factor-1α protein (HIF-1α) is a subunit of the HIF-1 transcription factor, which induces transcription of several genes involved in the cellular response to hypoxia.
Hypoxia-inducible factor 1-alpha, also known as HIF-1-alpha, is a subunit of a heterodimeric transcription factor hypoxia-inducible factor 1 (HIF-1) that is encoded by the HIF1A gene. It is a basic helix-loop-helix PAS domain containing protein, and is considered as the master transcriptional regulator of cellular and developmental response to hypoxia. The dysregulation and overexpression of HIF1A by either hypoxia or genetic alternations have been heavily implicated in cancer biology, as well as a number of other pathophysiologies, specifically in areas of vascularization and angiogenesis, energy metabolism, cell survival, and tumor invasion. Two other alternative transcripts encoding different isoforms have been identified.
Procollagen-proline dioxygenase, commonly known as prolyl hydroxylase, is a member of the class of enzymes known as alpha-ketoglutarate-dependent hydroxylases. These enzymes catalyze the incorporation of oxygen into organic substrates through a mechanism that requires alpha-Ketoglutaric acid, Fe2+, and ascorbate. This particular enzyme catalyzes the formation of (2S, 4R)-4-hydroxyproline, a compound that represents the most prevalent post-translational modification in the human proteome.
Endothelial PAS domain-containing protein 1 is a protein that is encoded by the EPAS1 gene in humans. It is a type of hypoxia-inducible factor, a group of transcription factors involved in the physiological response to oxygen concentration. The gene is active under hypoxic conditions. It is also important in the development of the heart, and for maintaining the catecholamine balance required for protection of the heart. Mutation often leads to neuroendocrine tumors.
Hypoxia-inducible factor 3 alpha is a protein that in humans is encoded by the HIF3A gene.
Egl nine homolog 2 is a protein that in humans is encoded by the EGLN2 gene. ELGN2 is a alpha-ketoglutarate-dependent hydroxylase, a superfamily of non-haem iron-containing proteins.
Hypoxia-inducible factor prolyl hydroxylase 2 (HIF-PH2), or prolyl hydroxylase domain-containing protein 2 (PHD2), is an enzyme encoded by the EGLN1 gene. It is also known as Egl nine homolog 1. PHD2 is a α-ketoglutarate/2-oxoglutarate-dependent hydroxylase, a superfamily non-haem iron-containing proteins. In humans, PHD2 is one of the three isoforms of hypoxia-inducible factor-proline dioxygenase, which is also known as HIF prolyl-hydroxylase.
Egl nine homolog 3 is a protein that in humans is encoded by the EGLN3 gene. ELGN3 is a member of the superfamily of alpha-ketoglutarate-dependent hydroxylases, which are non-haem iron-containing proteins.
Hypoxia-inducible factor 1-alpha inhibitor is a protein that in humans is encoded by the HIF1AN gene.
Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors (HIF-PHIs) also known as Hypoxia-Inducible Factor stabilizers are members of a class of new drugs that act by inhibiting prolyl hydroxylase which is responsible to break down the hypoxia-inducible factor (HIF) under normoxic conditions.
In molecular biology mir-210 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.
Hypoxia-inducible factor dioxygenase may refer to:
Alpha-ketoglutarate-dependent hydroxylases are non-heme, iron-containing enzymes that consume oxygen and alpha-ketoglutarate as co-substrates. They catalyse a wide range of oxygenation reactions. These include hydroxylation reactions, demethylations, ring expansions, ring closures and desaturations. Functionally, the αKG-dependent hydroxylases are comparable to cytochrome P450 enzymes, which use oxygen and reducing equivalents to oxygenate substrates concomitant with formation of water.
HIF prolyl-hydroxylase is an enzyme involved in the HIF signalling pathways, and is the target for a set of therapeutic drugs called HIF prolyl-hydroxylase inhibitors.
Prolyl 4-hydroxylase, transmembrane is a protein that in humans is encoded by the P4HTM gene.
