Biosyntheses

Porphyrins and chlorophylls are the most widespread natural pigments. They are associated with the energy-converting processes of respiration and photosynthesis in living organisms, and the synthesis of specific porphyrin derivatives is often motivated by the desire to perform similar processes in the test tube. The structurally and biosynthetically related corrins (e.g. vitamin B,j) catalyze alkylations and rearrangements of carbon skeletons via organocobalt intermediates. The biosyntheses of these chromophores are also of topical interest. 

Many naturally occurring substances are epoxides You have seen two examples of such compounds already m disparlure the sex attractant of the gypsy moth (Section 6 18) and m the carcinogenic epoxydiol formed from benzo[a]pyrene (Section 118) In most cases epoxides are biosynthesized by the enzyme catalyzed transfer of one of the oxy gen atoms of an O2 molecule to an alkene Because only one of the atoms of O2 is trans ferred to the substrate the enzymes that catalyze such transfers are classified as monooxy genases A biological reducing agent usually the coenzyme NADH (Section 15 11) is required as well... 

Bacteria require p-aminobenzoic acid to biosyn thesize folic acid a growth factor Structurally sul fanilamide resembles p-aminobenzoic acid and is mistaken for it by the bacteria Folic acid biosynthesis IS inhibited and bacterial growth is slowed suffi ciently to allow the body s natural defenses to effect a cure Because animals do not biosynthesize folic acid but obtain it in their food sulfanilamide halts the growth of bacteria without harm to the host... 

Uronic acids are biosynthetic intermediates m various metabolic processes ascorbic acid (vitamin C) for example is biosynthesized by way of glucuronic acid Many metabolic waste products are excreted m the urine as their glucuronate salts... 

Fatty acids are biosynthesized by way of acetyl coenzyme A The following sec tion outlines the mechanism of fatty acid biosynthesis... 

Prostaglandins arise from unsaturated C20 carboxylic acids such as arachidonic acid (see Table 26 1) Mammals cannot biosynthesize arachidonic acid directly They obtain Imoleic acid (Table 26 1) from vegetable oils m their diet and extend the car bon chain of Imoleic acid from 18 to 20 carbons while introducing two more double bonds Lmoleic acid is said to be an essential fatty acid, forming part of the dietary requirement of mammals Animals fed on diets that are deficient m Imoleic acid grow poorly and suffer a number of other disorders some of which are reversed on feed mg them vegetable oils rich m Imoleic acid and other polyunsaturated fatty acids One function of these substances is to provide the raw materials for prostaglandin biosynthesis... 

Write the structural formula and give the lUPAC name for the acid from which PGEi is biosynthesized The structure of PGEi is shown in... 

Isoprenoid compounds are biosynthesized from acetate by a process that involves sev eral stages The first stage is the formation of mevalonic acid from three molecules of acetic acid... 

FIGURE 26 8 The distribu tion of the C label in citronellal biosynthesized from acetate in which the methyl carbon was isoto pically enriched with C... 

Animals accumulate cholesterol from then diet but are also able to biosynthesize It from acetate The pioneering work that identified the key intermediates m the com plicated pathway of cholesterol biosynthesis was carried out by Konrad Bloch (Harvard) and Feodor Lynen (Munich) corecipients of the 1964 Nobel Prize for physiology or... 

Cholesterol is biosynthesized in the liver trans ported throughout the body to be used in a va riety of ways and returned to the liver where it serves as the biosynthetic precursor to other steroids But cholesterol is a lipid and isn t soluble in water How can it move through the blood if it doesn t dis solve in if The answer is that it doesn t dissolve but IS instead carried through the blood and tissues as part of a lipoprotein (lipid + protein = lipoprotein) The proteins that carry cholesterol from the liver are called low density lipoproteins or LDLs those that return it to the liver are the high-density lipoproteins or HDLs If too much cholesterol is being transported by LDL or too little by HDL the extra cholesterol builds up on the walls of the arteries caus mg atherosclerosis A thorough physical examination nowadays measures not only total cholesterol con centration but also the distribution between LDL and HDL cholesterol An elevated level of LDL cholesterol IS a risk factor for heart disease LDL cholesterol is bad cholesterol HDLs on the other hand remove excess cholesterol and are protective HDL cholesterol IS good cholesterol... 

Terpenes and related isoprenoid compounds are biosynthesized from isopentenyl pyrophosphate... 

The stmctures of each of the following are given within the chapter Identify the carbon atoms expected to be labeled with when each is biosynthesized from acetate enriched with in Its methyl group... 

The 20 ammo acids listed m Table 27 1 are biosynthesized by a number of different path ways and we will touch on only a few of them m an introductory way We will exam me the biosynthesis of glutamic acid first because it illustrates a biochemical process analogous to a reaction we discussed earlier m the context of amine synthesis reductive ammatwn (Section 22 10)... 

L Glutamic acid is not an essential ammo acid It need not be present m the diet because animals can biosynthesize it from sources of a ketoglutaric acid It is however a key intermediate m the biosynthesis of other ammo acids by a process known as transamination L Alanine for example is formed from pyruvic acid by transamination from L glutamic acid... 

Bile acids (Section 26 13) Steroid derivatives biosynthesized in the liver that aid digestion by emulsifying fats Bimolecular (Section 4 8) A process in which two particles re act in the same elementary step Biological isoprene unit (Section 26 8) Isopentenyl pyrophos phate the biological precursor to terpenes and steroids... 

Historically, many attempts have been made to systematize the arrangement of fatty acids in the glyceride molecule. The even (34), random (35), restricted random (36), and 1,3-random (37) hypotheses were developed to explain the methods nature utilized to arrange fatty acids in fats. Invariably, exceptions to these theories were encountered. Plants and animals were found to biosynthesize fats and oils very differently. This realization has led to closer examination of biosynthetic pathways, such as chain elongation and desaturation, in individual genera and species. 

Detailed accounts of the biosynthesis of the prostanoids have been pubUshed (14—17). Under normal circumstances arachidonic acid (AA) is the most abundant C-20 fatty acid m vivo (18—21) which accounts for the predominance of the prostanoids containing two double bonds eg, PGE2 (see Fig. 1). Prostanoids of the one and three series are biosynthesized from dihomo-S-linolenic and eicosapentaenoic acids, respectively. Concentrations ia human tissue of the one-series precursor, dihomo-S-linolenic acid, are about one-fourth those of AA (22) and the presence of PGE has been noted ia a variety of tissues (23). The biosynthesis of the two-series prostaglandins from AA is shown ia Eigure 1. These reactions make up a portion of what is known as the arachidonic acid cascade. Other Hpid products of the cascade iaclude the leukotrienes, lipoxins, and the hydroxyeicosatetraenoic acids (HETEs). Collectively, these substances are termed eicosanoids. 

Thiostrepton family members are biosynthesized by extensive modification of simple peptides. Thus, from amino acid iacorporation studies, the somewhat smaller (mol wt 1200) nosiheptide, which contains five thiazole rings, a trisubstituted iadole, and a trisubstituted pyridine, is speculated to arise from a simple dodecapeptide. This work shows that the thiazole moieties arise from the condensation of serine with cysteiae (159,160). Only a few reports on the biosynthesis of the thiostrepton family are available (159,160). Thiostrepton is presently used ia the United States only as a poly antimicrobial vetetinary ointment (Panalog, Squibb), but thiazole antibiotics have, ia the past, been used as feed additives ia various parts of the world. General (158) and mechanism of action (152) reviews on thiostrepton are available. 

Hybridalactone, a novel marine derived eicosanoid from Laurencia hybrida, appears to be biosynthesized by a unique pathway from eicosapentaenoic acid. The synthesis of hybridalactone was carried out enantiospecifically from (+)-bicyclo[3.2.0]hept-4-ene-l-one so as to provide proof of stereochemistry (Ref. 4). 

Leukotriene B5 can be biosynthesized in the body from eicosapentaenoic acid, which is ingested in the form of dietary fish lipid. Synthetic LTB5 was synthesized as outlined below and found to have only 20% of the neutrophil chemotactic activity of LTB4, a fact which may be relevant to the antiinflammatory effect of dietary marine lipid. 

The 11,12-oxido and 14,15-oxido analogs of leukotriene A4 were synthesized to help answer the question of whether these compounds might be biosynthesized from arachidonate by the 12- and 15-lipoxygenation pathways and serve as physiologic regulators. Hydrolysis products of the 14,15-oxide were later found to be formed in biological systems. 

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