## 3 Biosynthesis of Aromatic and Isoprenic Precursors of Prenylquinones in Parasitic Protozoa
### Aromatic Head Group Biosynthesis
#### 3.1.1 Amino Acid Degradation  
Generalities about Amino Acid Degradation  
There are several routes for the conversion of the aromatic amino acids tyrosine and phenylalanine to 4-hydroxybenzoate, 4-hydroxyphenylpyruvate (4 HPPP) and chorismate, which are required for the biosynthesis of all prenylquinones and other aromatic compounds. However, these pathways remain poorly studied in parasitic protozoa. Tyrosine degradation begins with nitrogen transfer from the aromatic amino acid to alpha ketoglutarate, generating glutamate and 4 HPPP. This reaction can be catalyzed by several aminotransferases, including tyrosine aminotransferase (TAT). Additionally, phenylalanine can be transformed to prephenate by the action of prephenate dehydratase and consecutively to 4 HPPP by prephenate dehydrogenase [62; 63; 64; 68; 89]. The enzyme 4-hydroxyphenylpyruvate dehydrogenase (HPPP) can convert 4 HPP to homogenistate, the aromatic precursor oftocopherol and PQ in plants [45].  
There exists another pathway for the conversion of amino acids to 4-hydroxybenzoate. This pathway starts with an oxidative deamination, catalyzed by the flavoenzyme L-amino acid oxidase, which converts tyrosine or other amino acids to the corresponding ketoacid while generating ammonia and hydrogen peroxide [90; 91]. In the second step of the pathway, the formation of 4-hydroxyphenyllactate (HPL) occurs via the action of a NAD\({}^{+}\)-dependent HPP reductase that has been previously studied in several plant models [92]. In the third step of the pathway, HPL is converted into 4-comamate by a mechanism not has been elucidated to date [93]. Then, in the fourth step of the pathway, 4-coumarate, ATP, and coenzyme A (CoA) react as substrates of the enzyme 4-comamate-CoA ligase, generating AMP, diphosphate and 4-coumaroyl-CoA [82]. [PERSON] et al. suggested that the fifth step can be performed by beta oxidation, in which 4-coumaroyl-CoA would be oxidatively decarboxylated to 4-hydroxybenzoyl-CoA at the expense of a CoA. In the sixth step of this enzymatic pathway, 4-hydroxybenzoyl-CoA derived from the previous reaction is hydrolyzed to a thioester group, generating 4-hydroxybenzoate [82].  
Figure 2: Scheme of chorismate synthesis from aromatic amino acids (tyrosine and phenylalanine) or the shikimate pathway. DAHP; PEP; TAT/ASAT (EC 2.6.1.5); HRPR (EC 1.1.1.237); U.E. (uncharacterized enzyme); 4 CL (EC 6.2.1.12); HBAT (EC 3.1.2.23); CL (EC 4.1.3.40); PDH (EC 1.3.1.12/1.3.1.13); PDT (EC 4.2.1.51); CM (EC 5.4.99.5); DAHPS (EC 2.5.1.54); DHQS (EC 4.2.3.4); DHQD (EC 4.2.1.10); SDH (EC 1.1.1.25/1.5.8/1.1.282); SK (EC 2.7.1.71); EPSPS (EC 2.5.1.19); CS (EC 4.2.3.5). Based on information from Kyoto Encyclopedia of Genes and Genomes database [87].  
Amino Acid Degradation in Parasitic Protozoa  
Conversion of the aromatic amino acids tyrosine and phenylalanine to 4-hydroxybenzoate, 4-hydroxyphenylpyruvate (4 HPPP), and chorismate remains poorly studied in parasitic protozoa. Only tyrosine degradation has been demonstrated to be essential in _Leishmania_ and this pathway seems to be an excellent drug target [63]. HPPD and TAT inhibitors have been shown to compromise tyrosine degradation andtocopherol biosynthesis in _Leishmania_ and _P. falciparum_[64; 90; 91]. Alternatively, prephanate can also be converted to chorismate by the chorismate mutase enzyme. Subsequently, chorismate can be converted to 4-hydroxybenzoate by the action of chorismate-pyruvate lyase, which is then used for vitamin K, UQ or PQ biosynthesis depending on the organism [45].