Palm Fruit Bioactives augment expression of Tyrosine Hydroxylase in the Nile Grass Rat basal ganglia and alter the colonic microbiome

Abstract

Tyrosine hydroxylase (TH) catalyzes the hydroxylation of L-tyrosine to L-DOPA. This is the rate-limiting step in the biosynthesis of the catecholamines – dopamine (DA), norepinephrine (NE), and epinephrine (EP). Catecholamines (CA) play a key role as neurotransmitters and hormones. Aberrant levels of CA are associated with multiple medical conditions, including Parkinson’s disease. Palm Fruit Bioactives (PFB) significantly increased the levels of tyrosine hydroxylase in the brain of the Nile Grass rat (NGR), a novel and potentially significant finding, unique to PFB among known botanical sources. Increases were most pronounced in the basal ganglia, including the caudate-putamen, striatum and substantia nigra. The NGR represents an animal model of diet-induced Type 2 Diabetes Mellitus (T2DM), exhibiting hyperglycemia, hyperinsulinemia, and insulin resistance associated with hyperphagia and accelerated postweaning weight gain induced by a high-carbohydrate diet (hiCHO). The PFB-induced increase of TH in the basal ganglia of the NGR was documented by immuno-histochemical staining (IHC). This increase in TH occurred equally in both diabetes-susceptible and diabetes-resistant NGR fed a hiCHO. PFB also stimulated growth of the colon microbiota evidenced by an increase in cecal weight and altered microbiome. The metabolites of colon microbiota, e.g. short-chain fatty acids, may influence the brain and behavior significantly.

How Do Preorganized Electric Fields Function in Catalytic Cycles? The Case of the Enzyme Tyrosine Hydroxylase

“…In this article, we demonstrate that the preorganized electric field exerts opposing effects on the two steps of the catalytic cycles of metalloenzymes. We focus on a recently characterized heme enzyme of l -tyrosine hydroxylases (TyrH), which catalyzes the aromatic hydroxylation of the substrate l -tyrosine (Tyr) to form the natural product intermediates l -3,4-dihydroxyphenylalanine (DOPA), , which is the rate-limiting step responsible for the biosynthesis of natural product catecholamines dopamine, norepinephrine, and epinephrine. − This kind of aromatic hydroxylation is common in the metabolism of xenobiotic compounds and in biosyntheses of natural products. − As shown in Scheme , the catalytic reactions of TyrH consist of two stages. The first stage involves the activation of H 2 O 2 to form the active species of Cpd I, while the second stage involves the Cpd I-mediated hydroxylation of l -Tyr to afford l -DOPA.…”

Microglia integration into human midbrain organoids leads to increased neuronal maturation and functionality

“…The uptake of the amino acids phenylalanine and tyrosine was higher in assembloids. Interestingly, tyrosine can be metabolized from phenylalanine, which can be metabolized to L‐DOPA and, after that, to dopamine (Weinberg et al, 2019). Further experiments assessing synapse pruning would be of great value to confirm these observations.…”

Microglia integration into human midbrain organoids leads to increased neuronal maturation and functionality

“…The uptake of the amino acids phenylalanine and tyrosine was higher in assembloids. Interestingly, tyrosine can be metabolized from phenylalanine, which can be metabolized to L-DOPA and, after that, to dopamine (Weinberg et al ., 2019). Further experiments assessing synapse pruning would be of great value to confirm these observations.…”