Table of contents

Abstract

Key words

List of Abbreviations

List of Figures

List of Tables

Introduction

Specific digestive enzyme therapy used in metabolic pathologies particularly in neonates and infants.

Human rhDNase therapy for Cystic Fibrosis and its associated RTIs

Asparaginase

Conclusion

References

Abstract

Enzymes have high catalytic efficiency and a great affinity. They are needed for all the chemical inter conversions which are required to support life and hasten the metabolic processes taking place in the body. It is these properties which make them different when compared to other types of drugs (Schibli et al. 2002); Enzymes are used in different therapeutic purposes. Digestive and metabolic enzymes are used with other therapies in the treatment of illnesses such as skin ulcers, leukemia, ulcers, Pompe’s disease, cardiovascular diseases, celiac disease, Parkinson’s disease, Fabry’s diseases, inflammation, pancreatic disorders and digestive disorders (Gonzalez et al. 1995; Schibli et al. 2002). Enzymes are also used in the diagnosis, monitoring and investigation of life threatening diseases. Medically important enzymes which have been produced by microorganisms are more consistent and more effective. The present paper will look into specific digestive enzyme therapy used in metabolic pathologies particularly in neonates and infants, human rhDNase therapy for Cystic Fibrosis and its associated RTIs and Asparaginase.

Key words

Enzymes, Recombinant human deoxyribonuclease 1, Cystic Fibrosis

List of Abbreviations

EcAII – Escherichia coli

SER – Smooth Endoplasmic Reticulum

CF- Cystic Fibrosis

CFTR – Cystic Fibrosis Transmembrane Conductance Regulator

RhDNase – Recombinant human deoxyribonuclease 1

ErA – Erwinia chrysanthemi

GALT – Galactose-1-phosphate uridyl transferase

List of Figures

Figure 1: Galactosemia due to lack of the GALT enzyme

Figure 2. Schematic illustration of the types of bonds occurring in mucous gel, illustrating potential targets for mucoactive agents

Figure 3. Schematic illustration of the types of bonds occurring in mucous gel, illustrating potential targets for mucoactive agents

Figure 4: DNase which enzymatically cleaves extra cellular DNA into shorter molecules

Figure 5: The addition of DNase to sputum

Figure 6: Image showing DNase depolymerizing sputum DNA filaments

List of Tables

Table 1: Enzymes and their therapeutic use

Table 2: Functions of Enzymes in Human Milk

Table 3: Table showing some of the enzymes present in infants

Table 4: Incidence of rhDNase-Related and Cystic Fibrosis–Related Adverse              Events

Table 5: Microbial therapeutic enzymes and their application

Introduction

Therapeutic enzymes are enzymes which are used medically or adjunct together with other enzymes for the treatment of diseases (Hwang et al.2013). Some of the therapeutic uses of enzymes include:

Table 1: Enzymes and their therapeutic use

Specific digestive enzyme therapy used in metabolic pathologies particularly in neonates and infants.

Enzymes are proteins which have unique abilities. They are found in living cells and are crucial for chemical reactions taking place in the body. Human milk has many enzymes which are of great benefit to the infant and they all have different functions (Gonzalez et al. 1995)

Table 1: Functions of Enzymes in Human Milk (Gonzalez et al. 1995; Colboum et al. 2007; Love et al. 1979)

Antiprotease helps in the protection of the mammary gland from proteolysis. Proteolysis is as a result of lysosomal proteases. They also ensure that proteolytic breakdown of milk proteins does not reach so that they can reach the infant while they are still intact (Ito et al. 1984; Wong et al. 2012). The enzymes in the human milk have antitryptic and antichymotryptic abilities and, as such, ensure that there is no absorption of endogenous and bacterial proteases in infants. This helps in the protection of other extra intestinal organs, for example, the liver.

The high activity of the Antiproteases taking place in the colostrums happens just as nonimmunoglobulin protein is being transferred from the intestine to the systemic circulation of the infant. The digestive enzymes that are present in milk, digestive lipase and amylase, play the role for the pancreatic which is yet to be fully developed in the infant. Amylase and lipase are stable and can stay for many years (Blake et al.2007). The antiprotease activity of milk could be the reason for the high stability of enzymes present in milk.

Amylase is crucial to the infant especially after it starts using starch supplements. It is also important when the formula having oligosaccharides which have been hydrolyzed by amylase is given to the infants who are still breastfeeding. Compared to the amylase activity in adults, which of infants is below 0.5%. Even after breastfeeding for a period of four to six months, the infant lacks endogenously produced amylase. This is produced from the salivary glands (Berseth et al.1996; Gonzalez et al. 1995). The adequate level needed for pancreas enzymes in an infant take about two years after the birth of the infant. Milk amylase is also important for infants who are suffering from pancreatic insufficiency that is as a result of cystic fibrosis and malnutrition. Milk amylase has been studied extensively in the last ten years due to its ability to compensate for the low pancreatic lipase in infants because of the bile salt-dependent lipase found in the enzyme.

Another enzyme that is nutritionally important for the fetus and the neonate is Arginine. It is important since it detoxifies ammonia and helps in the synthesis of molecules which are of great significance to the fetus. Some of these molecules include nitric acid, creatine and polyamines (Marini et al. 1987). One of the major causes of nutritional problems in preterm infants is the lack of Arginine (hypoargininemia) in their developing bodies. The lack of hypoargininemia in the infant’s body leads to hyperammonemia dysfunction. Other related nutritional problems because of lack of this enzyme include pulmonary, intestinal, cardiovascular and neurological dysfunctions. In addition to that, it may result in high rates of infant morbidity and mortality which is due to premature births (Karlson et al. 1993). Intestinal citruline and arginine synthesis (which is one of the main sources of arginine) is not adequately present in preterm neonates because of the limited expression of genes required for major enzymes such as lyase, pyrroline-5-carboxylate synthase and argininosuccinate synthase among others. Consequently, when these enzymes lack in the body, it leads to hypoargininemia. It is important to note that premature births on women usually happen prior to the normal perineal surge of cortisol (Cortisol is an inducer and its representative of major arginine-synthetic enzymes) (Nussbaum, 1985; Gonzalez et al. 1995; Colboum et al. 2007; Love et al. 1979). It is therefore important since it helps in the maturation of intestinal arginine synthesis present in neonates. There are other advantages for the administration of the cortisol treatment. Some of these advantages are; it helps in enhancing and promoting enteral feeding to preterm infants and this is important for the synthesis of arginine, citruline and polyamines taking place in the intestines. Secondly, it enhances the growth of the intestines, the integrity and motility of the intestines. Lastly, it helps organs to mature faster while restoring the full enteral system of feeding.

Table 2: Table showing some of the enzymes present in infants (Barton et al. 1991)