Hypoxia Inducing
Factors
By Melissa Ojeda

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

Structure    Function   Control