Searched for: data_source:HUMANCYC [All Organisms, All Data Sources]

Summary:  General Background |FRAME: CPD-8117| (GLA) is a polyunsaturated (18:3) ω-6 fatty acid (the 6 refers to the position of the first double bond from the methyl end of the fatty acid). It is synthesized from |FRAME: LINOLEIC_ACID| by Δ⁶ desaturase enzymes. Unlike its precursor, GLA is not an essential fatty acid, since humans possess a Δ⁶ desaturase enzyme. GLA is of major importance, being the precursor for the synthesis of several Δ⁶-desaturated fatty acids, such as |FRAME: ARACHIDONIC_ACID| and |FRAME: 5Z8Z11Z14Z17Z-EICOSAPENTAENOATE| (see |FRAME: PWY-5353|). Δ⁶-desaturated fatty acids have roles in the maintenance of membrane structure and function, in the regulation of cholesterol synthesis and transport, in the prevention of water loss from the skin, and as precursors of eicosanoids, including prostaglandins and leucotrienes |CITS: [1334266]|. About This Pathway Although humans possess a Δ⁶-desaturase, they lack a Δ¹² and Δ¹⁵ desaturases, and thus |FRAME:LINOLEIC_ACID|, the precursor for GLA biosynthesis, is an essential fatty acid that must be obtained through their diet. Desaturation reactions in humans require oxygen, and are catalyzed by a microsomal membrane-bound three-component enzyme complex that includes |FRAME: ENSG00000166347-MONOMER|, an |FRAME: ENSG00000100243-MONOMER|, and the fatty acid desaturase |FRAME: CPLX-7649|.

Summary:  |FRAME: ZYMOSTEROL| is an intermediate in the biosynthesis of |FRAME: CHOLESTEROL|, a major component in human membranes. In the first part of this pathway, starting at |FRAME: LANOSTEROL|, a sequence of two enzymatic reactions, involving |FRAME:YHR007C-MONOMER|, and |FRAME:YNL280C-MONOMER|, converts this tetracyclic triterpenoid to the sterol intermediate |FRAME: 44-DIMETHYL-824-CHOLESTADIENOL|. In the second part of the pathway, a set of three enzymes removes two methyl groups from the A ring of |FRAME: 44-DIMETHYL-824-CHOLESTADIENOL|, resulting in formation of |FRAME: ZYMOSTEROL|. The demthylation sequence starts with |FRAME:YGR060W-MONOMER|. This enzyme acts in three steps - it first adds a hydroxyl group to the methyl carbon, converting it to a hydroxylmethyl group. It continues by oxidation of the hydroxyl moiety resulting in a formyl group, and ends with the addition of a second hydroxyl group, generating a carboxyl group. This carboxyl is then removed by the second enzyme, |FRAME: YGL001C-MONOMER|. In the process of decarboxylation, a hydroxyl group attached to another carbon of the sterol ring is oxidized to a keto group, and in order to complete this cycle, the third enzyme, |FRAME: YLR100W-MONOMER|, restores it back to the initial hydroxyl group. When the first cycle is complete, |FRAME: 44-DIMETHYL-824-CHOLESTADIENOL| has been converted to |FRAME: 4-METHYL-824-CHOLESTADIENOL|, which is the substrate for a second round of activity. When the second cycle is complete, |FRAME: 4-METHYL-824-CHOLESTADIENOL| has been converted to |FRAME: ZYMOSTEROL|.

Summary:  Adenosine nucleotides can be synthesized de novo. In that route |FRAME: AMP AMP| (AMP) is synthesized via |FRAME: IMP IMP| (IMP) and |FRAME: ADENYLOSUCC adenylo-succinate| , which is converted to AMP by the action of |FRAME: ASL-MONOMER adenylosuccinate lyase| (see |FRAME: PWY-6126 adenosine nucleotides de novo biosynthesis|). Note that the free base |FRAME: ADENINE adenine| or the ribonucleoside |FRAME: ADENOSINE adenosine| are not produced via the de novo pathway. Many organisms can also recycle adenosine nucleotides by a combination of degradation and salvage pathways. The degradation pathways are responsible for the conversion of the nucleotides to the nucleoside (|FRAME: ADENOSINE adenosine|) and free base form (|FRAME: ADENINE adenine|), and further degradation to compounds that can be catabolized to basic building blocks (for example, see |FRAME: SALVADEHYPOX-PWY adenosine nucleotides degradation II|). However, both |FRAME: ADENOSINE adenosine| and |FRAME: ADENINE adenine| can be salvaged by certain enzymes, and be converted back to nucleotide form. The enzyme |FRAME: DEOD-CPLX "purine phosphorylase (DeoD)"| (EC 2.4.2.1) cleaves |FRAME: ADENOSINE adenosine| to |FRAME: ADENINE adenine| and |FRAME: RIBOSE-1P α-D-ribose-1-phosphate|, while a second enzyme, such as |FRAME: ADENPRIBOSYLTRAN-CPLX adenine phosphoribosyltransferase|, can utilize |FRAME: PRPP 5-phospho-α-D-ribose 1-diphosphate| to convert the free base to the mononucleotide |FRAME: AMP AMP|. Other routes from |FRAME: ADENOSINE adenosine| to |FRAME: AMP AMP| are described in |FRAME: PWY-6605 adenine and adenosine salvage II| and |FRAME: PWY-6619 adenine and adenosine salvage VI|. Either of these routes enables the organism to salvage the degradation products of adenosine nucleotides, and recycle them back to nucleotide form.

Summary:  |FRAME: SQUALENE| is a naturally occurring polyprenyl compound primarily known for its key role as an intermediate in sterol biosynthesis. The name originates from the scientific name for the shark (|FRAME: TAX-7796| spp.), since shark liver oil is considered the richest source of squalene. However, squalene is abundant in many plant oils, including olive oil, palm oil, wheat-germ oil, amaranth oil, and rice bran oil. Squalene is structurally similar to |FRAME: CPD1F-129|, and is produced in two steps from two molecules of |FRAME: FARNESYL-PP| which are joined and reduced by the enzyme |FRAME: AT4G34640-MONOMER|. After its biosynthesis, squalene can be transported to other areas of the body for incorporation into tissues (in humans, about 60 percent of dietary squalene is absorbed and transported in serum to be distributed ubiquitously in different tissues, with the greatest concentration in the skin |CITS: [9988781]|) or it can be further metabolized by the enzyme |FRAME: YGR175C-MONOMER|, generating |FRAME: EPOXYSQUALENE|. |FRAME: EPOXYSQUALENE| is substrate for |FRAME: ENSG00000160285-MONOMER|, an enzyme that generates |FRAME: LANOSTEROL|, a main gateway for the synthesis of all other sterols, including cholesterol (see |FRAME: PWY66-341|).

Summary:  |FRAME: INOSITOL-1-4-5-TRISPHOSPHATE| is a secondary messenger molecule used in signal transduction and lipid signaling. It mediates the biological response of a large number of hormones and neurotransmitters in target cells by regulating calcium release from intracellular stores. |FRAME: INOSITOL-1-4-5-TRISPHOSPHATE| is synthesized by hydrolysis of |FRAME: PHOSPHATIDYL-MYO-INOSITOL-45-BISPHOSPHA "phosphatidylinositol 4,5-bisphosphate"| (PIP2), a phospholipid that is located in the plasma membrane, by the action of phospholipase C, as described in |FRAME: PWY-6351|. Once formed, the levels of |FRAME: INOSITOL-1-4-5-TRISPHOSPHATE| are tightly regulated by two mechanisms. In the first mechanism the compound is dephosphorylated to |FRAME: INOSITOL-1-4-BISPHOSPHATE| |CITS: [6285891][6095097]|, initiating a pathway that recycles the inositol moiety to the plasma membrane as phosphatidylinositols. In the second mechanism, it is phosphorylated by inositol 1,4,5-trisphosphate 3-kinase to |FRAME: CPD-506|. This compound has been suggested to have roles in controlling calcium homeostasis, transferring calcium between intracellular stores, and/or regulating calcium entry across the plasma membrane |CITS: [1659392]|. It may also play a role in regulating cross-talk between the calcium and other signaling pathways. A |FRAME: CPD-506|-binding protein has been identified that can stimulate the GTPase activity of the ras and rap small GTP binding proteins |CITS: [7637787][9038348]|. |FRAME: CPD-506| can be cleaved to |FRAME: INOSITOL-1-3-4-TRIPHOSPHATE| |CITS: [3010126]|, or it could be phosphorylated further to |FRAME: CPD-1107| and eventually I|FRAME: MI-HEXAKISPHOSPHATE| |CITS: [2550825][2548474]|, as described in |FRAME: PWY-6361|. |FRAME: INOSITOL-1-3-4-TRIPHOSPHATE| links the degree and duration of receptor-dependent phospholipase C activation to the generation of |FRAME: CPD-178|, a cellular signal that regulates the ionic conductance of Cl-channels |CITS: [9660883][10383396][9838040]|.

Summary:  General Background |FRAME: MI-HEXAKISPHOSPHATE| (phytate, phytic acid) is one of the most prevalent forms of phosphorylated inositols in the cell, with a total concentration of 15-100 μM |CITS:[3426614][1684044][8435066]|. It's cellular distribution is not completely known - some of it is soluble, some is "wall-papered" around membranes, while some is bound to proteins |CITS: [9838040]|. The compound has been proposed to have a number of signaling roles, including regulation of insulin exocytosis |CITS: [9114007]|, regulation of nuclear mRNA export |CITS:[10390371][10683435]|, binding of the clathrin assembly proteins AP2 and AP3 |CITS: [1849645][1371119]|, inhibition of clathrin cage assembly |CITS: [7814377][7829485]|, and inhibition of serine and threonine protein phosphatases that are thought to regulate L-type Ca2+ channels |CITS: [9334307]|. About This Pathway Unlike the phytate biosynthetic pathway found in yeast, which proceeds directly from |FRAME: INOSITOL-1-4-5-TRISPHOSPHATE| by a series of successive phosphorylations (see |FRAME: PWY-6361|), the mammalian pathway uses a detour: |FRAME: INOSITOL-1-4-5-TRISPHOSPHATE| is first isomerized to |FRAME: INOSITOL-1-3-4-TRIPHOSPHATE| (via |FRAME: CPD-506|) |CITS: [3010126]|, and further phosphorylation proceeds from there |CITS: [15531582]|. The multiplicity of enzymes that catalyze inositol phosphate transformations and the lack of in vivo studies have made determining the pathway difficult. However, as more in vivo results became available, and as the catalytic efficiencies of the enzymes with different substrates were determined, it became clear that the main tetra-phosphate intermediate in the human pathway is |FRAME: CPD-505| |CITS: [12223481]|, supporting the pathway presented here |CITS:[2584198][15531582]|.

Summary:  General Background Polyamines such as |FRAME: SPERMINE| and |FRAME: SPERMIDINE| are required for normal cellular function through their interaction with cellular macromolecules. They are critical regulators of cell growth, differentiation and death. Their metabolism is complex and many mechanisms regulate their levels to maintain polyamine homeostasis, including transcriptional, translational and post-translational regulation. Polyamine research has been of particular interest in the development of drugs to treat parasitic infections and cancer. The three polyamines |FRAME: SPERMINE|, |FRAME: SPERMIDINE| and |FRAME: PUTRESCINE| are biosynthesized from |FRAME: ARG| (via |FRAME: L-ORNITHINE|) and |FRAME: MET| (see pathways |FRAME: ARGSPECAT-PWY|, |FRAME: BSUBPOLYAMSYN-PWY| and |FRAME: PWY-46|). Their degradation has been described as a retroconversion (or counter-conversion) of the biosynthetic process. Reviewed in |CITS: [13678416]| and |CITS: [16756494]|. Also see |FRAME: PWY-0|. About This Pathway The main mechanism for |FRAME: SPERMINE| and |FRAME: SPERMIDINE| degradation involves the use of |FRAME: ACETYL-COA| to convert them to N¹-acetylated derivatives in the cytosol (a rate-limiting, or regulatory step) controlled by the inducible enzyme spermidine/spermine N¹-acetyltransferase. This is followed by oxidation of the N¹-acetylated derivatives in perosxisomes by a peroxisomal polyamine oxidase that has a preference for acetylated substrates. In addition, a cytosolic spermine oxidase degrades |FRAME: SPERMINE| to |FRAME: SPERMIDINE|. In addition to their retroconversion to |FRAME: SPERMIDINE| or |FRAME: PUTRESCINE|, the N¹-acetylated derivatives are also exported from normal cells into the extracellular environment, as is |FRAME: PUTRESCINE|. However, they are found in high concentration inside cancer cells, which links altered polyamine metabolism with carcinogenesis. This is an active field of research. The direct conversion of |FRAME: SPERMINE| to |FRAME: SPERMIDINE| without acetylation, via spermine oxidase, is a more recent discovery and its significance to polyamine metabolism is under investigation. Reviewed in |CITS: [13678416] [16756494]| and |CITS: [17371265]|.

Summary:  General Background |FRAME: METHYL-GLYOXAL "Methylglyoxal"| is produced in small amounts during glycolysis (via |FRAME:DIHYDROXY-ACETONE-PHOSPHATE|), fatty acid metabolism (via |FRAME:ACETONE|), and protein metabolism (via |FRAME:AMINO-ACETONE|). |FRAME: METHYL-GLYOXAL "Methylglyoxal"| is highly toxic, most likely as a result of its interaction with protein side chains (see |CITS: [10597025]| for a review). There are several pathways for the detoxification of methylglyoxal, based on different enzymes that are able to convert methylglyoxal to less toxic compounds. These enzymes include glyoxalase enzymes, methylglyoxal reductases, aldose reductases, aldehyde reductases and methylglyoxal dehydrogenases. About This Pathway In this pathway, methylglyoxal is reduced to acetol by the action of various enymes possessing |FRAME: G7558-MONOMER| activity. Most of the enzymes that have been characterized with this activity belong to the family of NADPH-dependent aldo-keto reductases (AKRs). For example, the human aldose reductase (EC 1.1.1.21) and aldehyde reductase (EC 1.1.1.2) are both capable of reducing methylglyoxal to acetol |CITS: [1537826]|. Prolonged incubations of E. coli cell-free extracts with methylglyoxal resulted in conversion of acetol to |FRAME: PROPANE-1-2-DIOL| |CITS: [16077126]|. The enzyme proposed to catalyze this reaction is |FRAME:GLYCDEH-CPLX| |CITS: [6183251][3920199]|. In bacteria |FRAME: PROPANE-1-2-DIOL| is a dead-end metabolite and exits the cell rapidly |CITS: [2644239]|. The same reaction has also been observed in mammalian systems, where it is catalyzed by |FRAME:MONOMER-12905| |CITS: [1537826]|. In mammals |FRAME: PROPANE-1-2-DIOL| is metabolized in the liver to L-lactate |CITS: [1537826]|.