**4. The functional activities of Hsp70 in partnership with Hsp40**

Both heat shock protein 70 and heat shock protein 40 were first discovered in bacteria that were exposed to stressful conditions, thus these proteins were overexpressed in response to the challenging conditions the bacteria organism was faced with [30]. As a result, the cellular protein structure and functional activities were

**Figure 2.**

*Hsp70/Hsp40 partnership in folding process of newly synthesized proteins. Hsp40 hands over a newly synthesized protein to Hsp70 for proper folding with APT driven activity with help of nucleic exchange factor being at the Centre of the action. Unsuccessful protein folding are dealt with proteasome for degradation.*

affected, Hsp70 was able to rescue aggregated and misfolded proteins (**Figure 2**). The partnership between Hsp70 and Hsp40 plays a major role in helping misfolded proteins to fold and gain their functional activities [31, 32]. To successfully assist misfolded proteins or substrates to fold properly, Hsp70 recognized and bind into the hydrophobic patches. The major role played by Hsp40 is to recognized and present misfolded proteins into an ATP Hsp70 for folding. The ATP is hydrolyzed to ADP, which then allows the substrate to bind to the ADP Hsp70 for folding. Once properly folded, the ADP is then converted to ATP thus releases the properly folded protein. Taken together, newly synthesized protein requires the assistance of heat shock proteins to fold properly, otherwise, they can be toxic to the cells if they are not properly folded.

### **5. Biosynthesis of polyamines**

The synthesis of Polyamines such as putrescine, spermidine, and spermine is driven by *S-Adenosylmethionine decarboxylase* (AdoMetDC) and *Ornithine decarboxylase* (ODC). Both Adenosylmethionine and Ornithine function as precursors of polyamine biosynthesis [33, 34]. Unlike other species, *Plasmodium falciparum* AdoMetDC is connected to ODC which makes it an ideal drug target (**Figure 3**) [27]. These positively charged molecules are involved in various activities in the cellular system such as proliferation, differentiation, cell growth, protein synthesis, and RNA and DNA packaging [35]. In plants, polyamines have been reported to act as molecular chaperones or respond to heat shock to prevent plants. In addition to that, polyamines also prevent DNA damage of the cells exposed to UV radiation which could lead to cell death [35–37]. Taken together, this suggests that both polyamines and heat shock proteins are used by the parasite *Plasmodium falciparum*

#### **Figure 3.**

*Polyamines biosynthesis in* plasmodium falciparum *parasite. Biosynthesis of polyamines in* P. falciparum *is driven by linked S-adenosylmethionine decarboxylase (AdoMetDC) and ornithine decarboxylase (ODC). Whereas in mammalian cells AdoMetDC and ODC are not joined together. Abreviations: SpdSyn, spermidine synthase; Spd, spermidine; dcAdoMet, decarboxylated S-adenosylmethionine; SpmSyn, spermidine synthase; Spm, spermine.*

*A Double Line of Defense: Heat Shock Proteins and Polyamines Act as Contributing Factors… DOI: http://dx.doi.org/10.5772/intechopen.98852*

as a strategy to survive under unfavorable conditions when it enters the human host (where it experiences a sudden change of temperature) from the mosquito [38–45]. It could be that both polyamines and heat shock proteins contribute a lot to drug resistance that the parasite has demonstrated to current drugs available in the market. Therefore, understanding how these two molecules cooperate in the parasite could lead to the right direction in the development of alternative malarial treatment [28, 29, 32].
