DISTRIBUTION OF TYROSINE HYDROXYLASE IN HUMAN AND ANIMAL BRAIN¹

Abstract

The activity of tyrosine hydroxylase (EC 1.10.3.1) when assayed under ideal conditions in young human brains, was comparable to that in brains of other species in level of activity and distribution. The highest levels of activity were in the putamen, caudate nucleus and substantia nigra, in keeping with data on other species. The caudate activity in human brain appeared to decrease substantially with increasing age. In both humans and baboons, the enzyme in the neostriatum was particle‐bound and inhibited by the 2‐amino‐4‐hydroxy‐6,7‐dimethyltetrahydropteridine cofactor system. In the substantia nigra it was soluble and stimulated by the 2‐amino‐4‐hydroxy‐6,7‐dimethyltetrahydropteridine cofactor system. The data suggest that tyrosine hydroxylase may be produced in a soluble form in the cell bodies of the substantia nigra but become bound as it moves toward the nerve endings in the putamen and caudate nucleus. The bound form of the enzyme was unstable but the soluble form exhibited considerable stability.

Ageing and the nigrostriatal dopaminergic system

“…Initial in vitro work showed a significant decrease in nigral tyrosine hydroxylase (TH) activity with age (McGeer et al, 1971;Cote and Kremzner, 1974;McGeer et al, 1976McGeer et al, , 1977. The decline was exponential, with the most substantial losses occurring between the ages of 5-25 yrs.…”

“…Some studies have also reported equivocal or negative results, but as they employed non-standardized dissection methodology (Robinson et al, 1977), or the use of older sample groups which could not be expected to explore the effects of loss in early adult life (Grote et al, 1974;Mackay et al, 1978a), this may explain inconsistencies in findings. The predominant limitation of studies of this type is the extreme sensitivity of TH to pre-and post-mortem conditions, estimations of enzyme activity being particularly affected by the interval between death and freezing of tissue (McGeer et al, 1971(McGeer et al, , 1976. More recently, the use of immunolabelling to measure TH protein directly has overcome many of the problems created by postmortem delay.…”

Three-way Interaction between 14-3-3 Proteins, the N-terminal Region of Tyrosine Hydroxylase, and Negatively Charged Membranes

“…TH is essentially soluble and cytoplasmic (22), but a fraction is also found as membrane-bound both in brain, notably at nerve endings and synaptic vesicles (23)(24)(25), and in adrenal chromaffin cells, where it is associated with catecholamine secretory granules (23,26,27). It has further been shown that TH has affinity for isolated chromaffin granule membranes and negatively charged phospholipid layers (28,29).…”

Demonstration of Functional Coupling between Dopamine Synthesis and Its Packaging into Synaptic Vesicles

“…Nonspecific uptake of [ 3 H]DA was measured in the presence of CCCP. Since dual isotopes were applied, two separate channels were used for counting 14 C and 3 H activity.…”

“…L-Dopa is further decarboxylated by aromatic L-amino acid decarboxylase (AADC; EC 4.1.1.28) to form DA. In the central nervous system, TH has been shown to exist in two distinct forms, namely, soluble TH (STH) and membrane-bound TH (MTH) [13,14]. Alterations in the level of DA induced by TH or AADC in the central nervous system have been implicated in neurodegenerative diseases, including Parkinson's disease [19], Huntington's disease [1], and schizophrenia [10].…”