TABLE OF CONTENTS

TITLE PAGE        –         –         –         –         –         –         –         –         i

CERTIFICATION           –         –         –         –         –         –         –         ii

DEDICATION      –         –         –         –         –         –         –         –         iii

ACKNOWLEDGEMENTS       –         –         –         –         –         –         iv

TABLE OF CONTENTS          –         –         –         –         –         –         v

CHAPTER ONE: INTRODUCTION

1.1     Background Information          –         –         –         –         –         1

CHAPTER TWO: METABOLISM OF TYROSINE

2.1     Dietary Requirements and Sources of Tyrosine      –         –         5

2.2     Biosynthesis of Tyrosine –         –         –         –         –         –         7

2.3     Catabolism of Tyrosine   –         –         –         –         –         –         8

2.4     Medical Uses of Tyrosine          –         –         –         –         –         9

2.5     Tyrosine Metabolism       –         –         –         –         –         –         10

CHAPTER THREE: DISORDERS OF TYROSINE

           METABOLISM  –         –         –         –         –         –         –         13

3.1     Tyrosinaemia         –         –         –         –         –         –         –         16

3.1.1  Hereditary Tyrosinemia Type I  –         –         –         –         –         18

3.1.2  Hereditary Tyrosinemia Type II          –         –         –         –         21

3.1.3  Hereditary Tyrosinemia Type III         –         –         –         –         22

3.2     Alkaptonuria          –         –         –         –         –         –         –         25

3.3     Albinism      –         –         –         –         –         –         –         –         29

3.4     Hawkinsinuria       –         –         –         –         –         –         –         31

3.5     Diagnosis of  Disorders of Tyrosine Metabolism     –         –         33

3.6     Treatment of Disorders of Tyrosine Metabolism      –         –         35

CHAPTER FOUR: SUMMARY AND CONCLUSION

4.1     Summary     –         –         –         –         –         –         –         –         37

4.2     Conclusion –         –         –         –         –         –         –         –         38

References

CHAPTER ONE: INTRODUCTION

1.1     Background Information

Tyrosine is a precursor to neurotransmitters and increases plasma neurotransmitter levels (particularly dopamine and norepinephrine) (Deijen and Orlebeke, 2014), but has little if any effect on mood in normal subjects (Hao et al., 2021).

However, a number of studies have found tyrosine to be useful during conditions of stress, cold, fatigue (in mice), (Reinstein et al., 2015), prolonged work and sleep deprivation (Ellaway, 2001) with reductions in stress hormone levels, reductions in stress-induced weight loss seen in animal trials and improvements in cognitive and physical performance.

Tyrosine does not seem to have any significant effect on cognitive or physical performance in normal circumstances, but does help sustain working memory better during multitasking (Hao et al., 2021).

L-tyrosine and its derivative (L-DOPA, melanin, phenyl-propanoids and others) are used in pharmaceuticals, dietary supplements and food additives. Two methods were formerly used to manufacture L-tyrosine. The first involves the extraction of the desired amino acid from protein hydrolysates using a chemical approach. The second utilizes enzymatic synthesis from phenolics, pyruvate and ammonia through the use of tyrosine phenolyase (Hao et al., 2021). Advances in genetic engineering and the advent of industrial fermentation have shifted the synthesis of L-tyrosine to the use of engineered strains of E. coli.

A disease with autosomal recessive transmission, EIT-1 has a worldwide incidence of about 1 in 100,000. The incidence is higher in Northern Europe (1 per 8000) and in the Saguenay-Lac-st. Advances in the understanding of the pathophysiological of the disease process and new treatment options, such as an inhibitor of an early step in the degradation pathway, have improved the clinical course of affected persons dramatically (Reinstein et al, 2015).

The enzymatic defect in patients with tyrosinemia has been identified in fumarylacetoacetate hydrolase (FAH), the final step in the tyrosine degradation process. More than 100 mutations in fumarylacetoacetate(FAH) have been found in patients with HT-I, but no clear correlation between FAH genotype and HT -phenotype has been appreciated. FAH deficiency leads to accumulation of the upstream metabolites fumarylacetoacetate (FAH) and methylacetate which are then converted to the toxic intermediate succinylacetate (SAA) and succinylacetone (SA). Fumarylacetoacete has been shown to deplete blood and liver of glutathione, the consequence of which may be augmentation of the mutagenic potential of FAA. succinylacetone.

Succinylacetone (SA) also inhibits DNA ligase activity in fibroblasts isolated from patients with HT-1. Over time, the combined effects of high levels of fumarylacetoacetate and succinylacetone on the integrity of DNA and cellular repair mechanism may account for increased chromosomal breakage in fibroblasts isolated from patients with HT-1, as well as increased risk of HCG (Booth et al., 2020).

L-tyrosine or tyrosine or 4 hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is non-essential amino acid with a polar side group. The word “tyrosine is from the Greek tyro’s, meaning cheese, as it was first discovered in 1846 by German Chemist Justus Von Liebig in the protein casein from cheese (Harper, 2020). It is called tyfosyl when referred to as a functional group or side chain. While tyrosine is generally classified as a hydrophobic amino acid, it is more hydrophilic than phenylalanine (Harper, 2020).