Cytoplasm folates

In mammals and in the majority of bacteria, cobalamin regulates DNA synthesis indirectly through its effect on a step in folate metabolism, catalyzing the synthesis of methionine from homocysteine and 5-methyltetrahydrofolate via two methyl transfer reactions. This cytoplasmic reaction is catalyzed by methionine synthase (5-methyltetrahydrofolate-homocysteine methyl-transferase), which requires methyl cobalamin (MeCbl) (253), one of the two known coenzyme forms of the complex, as its cofactor. 5 -Deoxyadenosyl cobalamin (AdoCbl) (254), the other coenzyme form of cobalamin, occurs within mitochondria. This compound is a cofactor for the enzyme methylmalonyl-CoA mutase, which is responsible for the conversion of T-methylmalonyl CoA to succinyl CoA. This reaction is involved in the metabolism of odd chain fatty acids via propionic acid, as well as amino acids isoleucine, methionine, threonine, and valine. 

E. J. Smart, C. Mineo, and R. G. Anderson. Clustered folate receptors deliver 5-methyltetrahydrofolate to cytoplasm of MA104 cells. J. Cell Biol. 134 1169-1177 (1996). 

However, lack of utilization of exogenous folate may not fully explain the apparently indispensable nature of the synthesis of 7,8-dihydropteroate in plasmodium, toxoplasma, and eimeria. It is known that most of the folate molecules in mammalian cells are linked with polyglutamates in the cytoplasm and are transported across cell membranes with difficulty. It may compound the problem of obtaining 7,8-dihydropteroate or dihydrofolate for the parasite and makes all of the enzymes... 

Non-clathrin-coated pit internalization can occur through smooth imagination of 150-300 nm vesicles or via potocytosis. This pathway has been shown to be involved in the transport of folate and other small molecules into the cytoplasm. Plasmids are taken up by muscles through the T-tubules system and caveolae via potocytosis. Muscle cells appear to take up plasmids through the T-tubule system and caveolae via potocytosis. Apart from coated or uncoated pit pathways, cells may also take up plasmid/cationic carrier complexes via plasma membrane destabilization. Particles greater than 200 nm in diameter are not... 

Mimosine (9) is an agonist in folate metabolism and suggested to be an inhibitor toward the iron-containing ribonucleotide reductase, the activity of the transcription of the cytoplasmic serine hydroxymethyltransferase gene (shmtl ) and the copper enzymes... 

FIGURE 9.13 Complete OKidation of fholin to carbon dioitido The oxidation of choline to COj requires the participation pf enzymes of the mitochondria and cytoplasm, This means that some of the intermediates are expected to leave and reenter the mitochondria in the course of the pathway The pathway involves the participation of three folate-requiring enzymes. Betaine-ho-moeyatcinc methyltransferase is not a folate-requiring enzyme. 

Suboptimal erythropoiesis can be classified by changes in the size of RBCs noted on examination of the peripheral blood. Because the excretory and endocrine functions of the kidney usually mirror each other, renal dysfunction can lead to anemia by reduction in EPO production, resulting in a normochromic, normocytic pattern. Other causes of insufficient erythropoiesis include replacement of bone marrow by fibrosis, solid tumors, or leukemia, as well as defects in erythroid maturation. Relative deficiencies in the cofactors required for heme-RBC synthesis such as iron, folate, and vitamin B may also be important contributors. Structurally, RBC macrocytosis denotes defects in the maturation of the nucleus, whereas microcytosis is indicative of cytoplasmic defects (reduced hemoglobin synthesis). (A detailed description regarding the pathogenesis and treatment of anemic disorders is found in Chap. 99.)... 

In vitamin B12 or folate deficiency anemia, megaloblastosis results from interference in fohc acid-and vitamin B -interdependent nucleic acid synthesis in the immature erythrocyte. The rate of RNA and cytoplasm production exceeds the rate of DNA production. The maturation process is retarded, resulting in immature large RBCs (macrocytosis). Synthesis of the RNA and DNA necessary for cell division depends on a series of reactions catalyzed by vitamin B12 and folic acid, as they have a role in the conversion of midine to thymidine. As shown in Fig. 99-4, dietary folates are absorbed in this process and converted (A) to 5-methyl tetrahydrofolate, which is then converted via a Bi2-dependent reaction (B) to tetrahydrofolate (C). After gaining a carbon, tetrahydrofolate is converted to a folate cofactor (D), 5,10-methyl-tetrahydrofolate, used by thymidylate synthetase (E) in the... 

The cytoplasmic, mitochondrial, and chloroplast compartments are all involved in aspects of folate coenzyme metabolism in eukaryotic organisms. 

These hematopoietic precursor cells when exposed to too little folate and/or vitamin B12 show slowed cell division, but cytoplasmic development occurs at a normal rate. Hence, the megaloblastic cells tend to be large, with an increased ratio of RNA to DNA. Megaloblastic erythroid progenitors are usually destroyed in the bone marrow (although some reach the circulation). Thus, marrow cellularity is often increased but production of red blood cells is decreased, a condition called "ineffective erythropoiesis."... 

Deficiencies of folate or vitamin B12 can canse megaloblastic anemia, in which the cells are larger than normal. Folate and B12 are reqnired for DNA synthesis (see Chapters 40 and 41). When these vitamins are deficient, DNA replication and nnclear division do not keep pace with the matnration of the cytoplasm. Conseqnendy, the nuclens is extraded before the requisite number of cell divisions has taken place, and the cell volume is greater than it should be, and fewer blood cells are produced. 

Folate metabolism is not limited to the cytoplasmic compartment. Most of the folate in tissues is found in the mitochondrion and cytosol (Horne et al. 1997). Individual folate-dependent pathways are compartmentalized within organelles. The cytoplasmic and mitochondrial compartments each possess a parallel array of enzymes catalysing the interconversion of folate coenzymes that carry one-carbon units. The mitochondrial folate metabolism favours incorporation of one-carbon groups from serine and release of formate, while the cytoplasmic metabolism favours incorporation of one-carbon units from formate with purine and thymidine synthesis and homocysteine remethylation. 

The shikimic acid pathway leading to the production of chorismic acid is regulated in the cytosol of the fungal cells. Cytosol or intracellular fluid (cytoplasmic matrix) is a complex mixture of substances dissolved in water. These include ions (such as calcium, sodium, and potassium), macromolecules, and large complexes of enzymes that act together to carry out metabolic pathways. Production of chorismic acid in the cytosol is ultimately utilized in the synthesis of folate, ubiquinone, and amino acids, the most important of which is tryptophan which plays a major role in the biosynthesis of psilocybin. 

The cytological abnormalities which occur in megaloblastic anemia are similar regardless of whether the primary defect is in folate or vitamin 62 2 status. A marked leukopenia is observed in peripheral blood smears and there are many morphologic abnormalities in red and white blood cell precursors in the bone marrow. Megaloblastic white cell precursors display nuclear-cytoplasmic asynchronism which suggests deranged DNA synthesis. 

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