I..Introduction
II.Structure
III.Subtopic
IV.References
Introduction
What is hypoxia?
Hypoxia is a condition when the tissues are deprived
of oxygen. There are four types of hypoxia that include hypoxemic, anemic,
stagnant, and histotoxic. Hypoxemic hypoxia is produced when there is low
partial pressure of oxygen in the air, for example at high altitudes. Also
anything that would reduce the ventilation some examples include drugs
like anaesthetics and analgesics. Anaemic hypoxia is when the concentration
of hemoglobin is reduced. Anaemic hypoxia is when there are low levels
of iron , vitamin B12, and copper. Stagnant hypoxia is when there
is a low level oxygen to the tissues that is caused by reduced blood flow.
Lastly there is cytotoxic hypoxia occurs when the respiring cells in the
tissues are prevented from using oxygen [6].When tissues are deprived of
oxygen many diseases and illnesses result. Hypoxia inducing factor is a
specific protein involved in maintaining oxygen homeostasis and regulates
hypoxia inducible genes that include human erythropoietin (EPO) gene [1].
Structure
HIF-1
is a a heterodimer double helix loop and is the transcriptional factor
that is needed for the activation mediated by EPO gene enhancer in hypoxic
cells. HIF-1 consist of four chains: A, B, C, and D. Chains A and B is
the DNA molecule [4].
HIF-1 alpha is upregulated when there is lack
of oxygen and heterdimerizes with the receptor nuclear translocator also
known as the HIF-1 beta. The heterodimer complex
binds and activates transcription of target genes.
Chain A:
DNA
Consists of 14 bases, sequence is
G-C-C-C-T-A-C-G-T-G-C-T-G-C
Molecular weight is 4705 [3].
Chain B:
DNA
Consists of 14 bases, sequence
is G-C-A-G-C-A-C-G-T-A-G-G-G-C
Molecular weight is 4835 [3].
Chain C:
Beta unit known as Ary Hydrocarbon
Receptor Nuclear Translocator.
Molecular weight is 6852.
There are 59 residues [3].
Chain D:
Alpha unit known as Hypoxia
Inducible Factor 1 Alpha
Highly regulated by oxygen
concentration and determines levels of HIF-1 activity [2].
Molecular weight os 6959.
There are 59 residues [3].
Subtopic
Human Hypoxia-Inducible Factor 1-alpha Gene: HIF1A Structure and Evolutionary Conservation
HIF-1 factor consists of apha
and beta subunits. The alpha is encoded by HIF-1A and Hifa loci
on the human chromosome 14q21-24. The human and
mouse share about 90% of amino acid identity.
With this information it is concluded that there
is some evolutionary selection for HIF-1 [2].
References
1) Cohen, Harvey J., Ashima, Madan, and Sushama
Varma. "Co-Transactivation of the 3' Erythropoietin
Hypoxia Inducible Enhancer by the HIF-1 Protein."
Blood
Cells, Molecules, and Diseases. 31 May 1997:
169-176.
2) Iyer, Narayan V., Sandra W. Leug, and Gregg
L. Semenza. "The Human Hypoxia Inducible Factor 1alpha
Gene: HIF1A Structure and Evolutionary
Conservation" Genomics 22 May 1998: 159-165.
3) http://www.biochem.ucl.acuk/bsm/pdbsum/1d7g/main.html
4) http://www.rcsb.org/pdb/cgi/explore.cgi?job
5) http://www.imb-jena.de/cgi-bin/P/PDBscan.pl?code=1d7g
6) http://www.umds.ac.uk/physiology/rbm/hypoxes.htm