Amino acid active transport

The dopamine precursor l-DOPA (levodopa) is commonly used in TH treatment of the symptoms of PD. l-DOPA can be absorbed in the intestinal tract and transported across the blood-brain barrier by the large neutral amino acid (LNAA) transport system, where it taken up by dopaminergic neurons and converted into dopamine by the activity of TH. In PD treatment, peripheral AADC can be blocked by carbidopa or benserazide to increase the amount of l-DOPA reaching the brain. Selective MAO B inhibitors like deprenyl (selegiline) have also been effectively used with l-DOPA therapy to reduce the metabolism of dopamine. Recently, potent and selective nitrocatechol-type COMT inhibitors such as entacapone and tolcapone have been shown to be clinically effective in improving the bioavailability of l-DOPA and potentiating its effectiveness in the treatment of PD. 

Methyldopa (dopa = dihydroxy-phenylalanine), as an amino acid, is transported across the blood-brain barrier, decarboxylated in the brain to a-methyldopamine, and then hydroxylat-ed to a-methyl-NE The decarboxylation of methyldopa competes for a portion of the available enzymatic activity, so that the rate of conversion of L-dopa to NE (via dopamine) is decreased. The false transmitter a-methyl-NE can be stored however, unlike the endogenous mediator, it has a higher affinity for a2- than for ai-receptors and therefore produces effects similar to those of clonidine. The same events take place in peripheral adrenergic neurons. 

The brush border of the villi hydrolyses oligosaccharides to glucose, fructose and galactose. Microvilli also attach peptidases, which hydrolyse di-and tripeptides to amino acids. The monosaccharides and amino acids are transported into the blood by active transport processes. 

On the other hand, amino acids are transported inside the cell by different transporters. To date, 15 transport systems have been identified for amino acids in Sac-charomyces cerevisiae (Barre et al. 1998) and all of them are symport systems coupled to the entry of a proton. This proton must also be sent outside the cell in order to maintain the cellular homeostasis. Therefore, the uptake of ammonium and amino acids must be considered as active transport because it consumes ATP via H+-ATPase. 

The uptake of essential trace elements, e.g. Na, K, Ni, Co, Mg , POj", MoOj" and, in the case of auxotrophic mutants, of coenzymes, vitamins, and amino acids requires transport systems. In addition to Na transport (see previous sections), active transport systems for Ni, K, PO3, coenzyme M (H-S-CoM), methyl-coenzyme M (CH3-S-C0M), isoleucine and other branched-chain amino acids have been described in methanogens (for recent literature on ion transport in prokaryotes see refs. [251,252]). 

Kanai Y, Segawa H, Miyamoto K, Uchino H, Takeda E, Endou H. 1998. Expression cloning and characterization of a transporter for large neutral amino acids activated by the heavy chain of 4F2 antigen CD98. J. Biol. Chem. 273 23629-32... 

Fig.2.10 Phosphoglycerate utilization, (a) During the day. Photosynthesis in the chloroplast makes starch until there is no more room. The Calvin cycle continues to make triose phosphate, which exits the chloroplast in exchange for organic phosphate (Pi) entering the chloroplast and converting ADP to ATP. In the cytosol, the triose phosphate is mostly converted to sucrose but also to small amounts of other compounds such as amino acids for transport throughout the plant, (b) During the night. Phosphorylase is activated and it breaks up the starch to glucose 6-phosphate from which triose phosphate is made. The triose phosphate is exchanged for Pi. The Pi is a substrate for phosphorylase and keeps it active. Once in the cytosol, the triose phosphate is transferred mostly to mitochondria for respiration...

PPi is made in three ways (1) in the nucleus as a by-product of RNA synthesis (nNTP —> NMPn + nPPi) (2) in the cytosol as a by-product of amino acid activation for protein synthesis (aa + ATP —> aaAMP + PPi) and (3) by acetyl CoA synthetase on the outer mitochondrial membrane prior to its degradation for ATP production (R-COOH + ATP + HS-CoA —> R-Co-SCoA + AMP + PPi). Amino acid activation is the major source of cytosolic PPi, which is transported by the ANK protein to the osteoid matrix to inhibit premature mineralization (see Sect. 9.3.5). 

Free amino acids are transported into enterocytes by four active, carrier-mediated, Na+-dependent transport systems remarkably similar to the system for glucose. These systems transport, respectively, neutral amino acids basic amino acids (Lys, Arg, His) and cystine aspartic and glutamic acids and glycine and imino acids. Some amino acids (e.g., glycine) have affinities for more... 

Intracellular metabolism of amino acids requires their transport across the cell membrane. Transport of L-amino acids occurs against a concentration gradient and is an active process usually coupled to Na -dependent carrier systems as for transport of glucose across the intestinal mucosa (Chapter 12). At least five transport systems for amino acids (with overlapping specificities) have been identified in kidney and intestine. They transport neutral amino acids, acidic amino acids, basic amino acids, ornithine and cystine, and glycine and proline, respectively. Within a given carrier system, amino acids may compete for transport (e.g., phenylalanine with tryptophan). Na+-independent transport carriers for neutral and lipophilic amino acids have also been described, d-Amino acids are transported by simple diffusion favored by a concentration gradient. 

Intestinal transport studies with a variety of amino acids have demonstrated that amino acids (except dicarboxylic acid) are transported across the intestinal wall against a concentration gradient, and chemical energy is necessary for the transport. Adding cyanide or dinitrophenol to the incubation mixture inhibits amino acid transport. The active transport is specific for the L isomer the D isomer may be transported across the mucosa through passive diffusion. Although different carrier systems seem to exist, a given carrier system probably is shared by several amino acids. This explains the competition between amino acids for transport, and the simultaneous malabsorption of several amino acids in inborn errors of metabolism... 

Protein biosynthesis occurs in ribosomes, the cellular assembly factory where amino acids are covalently linked into a polypeptide chain along the template mRNA. The amino acids are transported into the ribosome in an activated state via coupling to specific carriers known as transfer RNAs (tRNA). The selection of specific amino acids from the cellular pool of amino acids (Tables 1.2 and 1.3) and the task of charging to cognate tRNAs are performed by specific aminoacyl-... 

CycHc adenosine monophosphate (cAMP), produced from ATP, is involved in a large number of ceUular reactions including glycogenolysis, Hpolysis, active transport of amino acids, and synthesis of protein (40). Inorganic phosphate ions are involved in controlling the pH of blood (41). The principal anion of interceUular fluid is HP (Pig. 3) (41). 

---