Biosynthetic precursors

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... 

Testosterone promotes muscle growth deepening of the voice the growth of body hair and other male secondary sex characteristics Testosterone is formed from cholesterol and IS the biosynthetic precursor of estradiol the principal female sex hormone or estrogen Estradiol is a key substance m the regulation of the menstrual cycle and the reproductive process It is the hormone most responsible for the development of female secondary sex characteristics... 

Carotenoids absorb visible light (Section 13 21) and dissipate its energy as heat thereby protecting the organism from any potentially harmful effects associated with sunlight induced photochemistry They are also indirectly involved m the chemistry of vision owing to the fact that p carotene is the biosynthetic precursor of vitamin A also known as retinol a key substance m the visual process... 

Acetyl coenzyme A is the biosynthetic precursor to the fatty acids, which most often occur naturally as esters Fats and oils are glycerol esters of long chain carboxylic acids Typically these chains are unbranched and contain even numbers of carbon atoms... 

Section 26 11 The triterpene squalene is the biosynthetic precursor to cholesterol by the pathway shown in Figure 26 10... 

FIGURE 27 5 Tyrosine is the biosynthetic precursor to a number of neurotransmit ters Each transformation IS enzyme catalyzed Hydroxy lation of the aromatic ring of tyrosine converts it to 3 4 dihyd roxyphenylalanine (l dopa) decarboxylation of which gives dopamine Hy droxylation of the benzylic carbon of dopamine con verts It to norepinephrine (noradrenaline) and methy lation of the ammo group of norepinephrine yields epi nephrine (adrenaline)... 

The biosynthetic precursor of PGEi is as as as icosa 8 11 14 tnenoic acid... 

Over 250 analogues of the B vitamers have been reported (11,100). Nearly all have low vitamin B activity and some show antagonism. Among these are the 4-deshydroxy analogue, pyridoxine 4-ethers, and 4-amino-5-hydroxymeth5i-2-methyipyrimidine, a biosynthetic precursor to thiamine. StmcturaHy unrelated antagonists include dmgs such as isoniazid, cycloserine, and penicillamine, which are known to bind to pyridoxal enzyme active sites (4). 

A class of 5,6,15- and 5,14,15-trioxygenated metabolites of arachidonate has been described by Samuelsson et al. Two of these compounds, termed lipoxins A and B, have recently been assigned the structures shown below. 1 Outlined below is a synthesis of a putative biosynthetic precursor of these compounds. Syntheses of the structures assigned to lipoxins A and B have also been accomplished.3.4... 

Phosphatidic acids not only are intennediates in the biosynthesis of triacylglycerols but also are biosynthetic precursors of other members of a group of compounds called phosphoglycerides or glycerol phosphatides. Phosphorus-containing derivatives of lipids are known as phospholipids, and phosphoglycerides are one type of phospholipid. 

The introduction to Section 26.8 pointed out that mevalonic acid is the biosynthetic precursor of isopentenyl pyrophosphate. The eariy steps in the biosynthesis of rnevalonate from three molecules of acetic acid are analogous to those in fatty acid biosynthesis (Section 26.3) except that they do not involve acyl canier protein. Thus, the reaction of acetyl coenzyme A with rnalonyl coenzyme A yields a molecule of acetoacetyl coenzyme A. 

Cholesterol is biosynthesized in the liver, transported throughout the body to be used in a variety 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 dissolve in it 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 biosynthetic precursor of PGEi is cA,( ,( -icosa-8,ll,14-trienoic acid. 

Flexibilene, a compound isolated from marine coral, is the only known terpenoid to contain a 15-membered ring. What is the structure of the acyclic biosynthetic precursor of flexibilene Show the mechanistic pathway for the biosynthesis. 

The biomimetic approach to total synthesis draws inspiration from the enzyme-catalyzed conversion of squalene oxide (2) to lanosterol (3) (through polyolefinic cyclization and subsequent rearrangement), a biosynthetic precursor of cholesterol, and the related conversion of squalene oxide (2) to the plant triterpenoid dammaradienol (4) (see Scheme la).3 The dramatic productivity of these enzyme-mediated transformations is obvious in one impressive step, squalene oxide (2), a molecule harboring only a single asymmetric carbon atom, is converted into a stereochemically complex polycyclic framework in a manner that is stereospecific. In both cases, four carbocyclic rings are created at the expense of a single oxirane ring. 

The fungus Streptomyces erythreus is the source of a number of structurally related macrolide antibiotics that are collectively known as the erythromycins. The erythromycins occupy a prominent position in medicine by virtue of their useful antibacterial properties. Their use in therapy over the course of the last three decades has been widespread, and has resulted in the saving of many human lives. In this chapter, we address the landmark total synthesis of erythronolide B (1), the biosynthetic precursor of all the erythromycins, by E.J. Corey and his coworkers which was carried out at Harvard in the 1970s.1... 

Figure 11.10 Biosynthetic precursors to the carbon skeleton of FR900482.

It is likely that the madurastatins are biosynthesized on a nonribosomal peptide synthetase, from salicylic acid as the starter acid. L-Serine is probably the precursor to the aziridine moiety, with epimerization occurring on the enzyme-bound amino acid as found for other nonribosomal peptides, with aziridine formation occurring at a late stage. Compounds 120 and 123 could therefore be biosynthetic precursors to 119 and 122, respectively. 

The cis P-lactams 57 are shown to act as cholesterol absorption inhibitors <96BMCL1947> and 58, an analogue of the dipeptide Phe-Gly methyl ester, is a protease inhibitor <96BMCL983>. A straightforward synthesis of proclavaminic acid 59, a biosynthetic precursor of clavulanic acid, is reported <96TA2277>. 

N-methyltyramine, the immediate biosynthetic precursor of hordenine, was synthesized and nitrosated in aqueous acid. The major product was U-hydroxy-3-nitro-N-nitroso-N-methylphenethylamine. 

Because of a supposedly statistical cleavage of the biosynthetic precursor of heparin, and uneven distribution of incompletely transformed residues (see Sections II and VI), chains that constitute conventional heparin differ from each other, both in average length and in sulfation pattern. 

Fig. 15.1. The A/-glycan biosynthetic pathway, illustrating how the three classes of A/-glycans (high mannose, hybrid and complex glycans) are derived from a common biosynthetic precursor. The trimannosyl-chitobiose core, which is common to all A/-glycans, is outlined on the precursor A/-glycan. Glc, o Man, GIcNAc.

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