Nature’s enolate equivalents: lysine enamines and coenzyme A

Nature breaks down glucose to produce energy, and in doing so produces smaller molecules which enter the citric acid cycle and are converted ultimately to carbon dioxide. In the other direction, the six-carbon sugar fructose can be made from two three-carbon fragments. The key reaction in both cases is the step in which the C–C bond linking the two C₃ sugars is formed or broken. The C₃ sugars are glyceraldehyde and dihydroxyacetone, both as their phosphate esters, and the reaction between then is an aldol condensation. The enol of dihydro xyacetone phosphate attacks the electrophilic aldehyde carbonyl group of glyceraldehyde 3-phosphate, catalysed by an enzyme named aldolase. The product is a ketohexose (i.e. a six-carbon sugar with a ketone carbonyl group), fructose-1,6-bisphosphate.

No enolate ion is formed in this aldol reaction. Instead a lysine residue in the aldolase enzyme forms an imine with the keto-triose.

Proton transfers allow this imine to be converted into an enamine, which acts as the nucleophile in the aldol reaction. Stereochemical control (it’s a syn aldol) comes from the way in which the two molecules are held by the enzyme as they combine. The product is the imine, which is hydrolysed to the open-chain form of fructose-1,6-bisphosphate.

Many other reactions in nature use enamines, mostly those formed from lysine. However, a more common enol equivalent is based on thiol esters derived from coenzyme A. Coenzyme A is an adenine nucleotide at one end, linked by a 5′-pyrophosphate to pantothenic acid, a com pound that looks rather like a tripeptide, and then to an amino thiol. Here is the structure broken down into its parts.

By now you will realize that most of this molecule is there to allow interaction with the various enzymes that catalyse the reactions of coenzyme A. Coenzyme A is conveniently abbreviated in structures to CoASH, where the SH is the vital thiol functional group, and all the

reactions we will be interested in are those of esters of CoASH. These are thiol esters, as opposed to normal alcohol esters, and the difference is worth a few comments. Thiol esters are less conjugated than ordinary esters, and ester hydrolysis occurs more rap idly with thiol esters than with ordinary esters because in the rate-determining step (nucleophilic attack on the carbonyl group) there is less conjugation to destroy. The thiolate is also a better leaving group.

Another reaction that goes better with thiol esters than with ordinary esters is enolization. This is an equilibrium reaction and the enol has lost the conjugation present in the ester. Again, a thiol ester has less to lose so is more enolized, and it is the enolization of thiolesters of coenzyme A that we are now going to discuss. We mentioned the citric acid cycle earlier but we have not so far discussed the chemistry involved. The citric acid cycle allows metabolism to shunt carbon atoms between small mol ecules, and the key step is the synthesis of citric acid from oxaloacetate and acetyl CoA. The reaction is essentially an aldol reaction between the enol of an acetate ester and an electro philic ketone, and the enzyme which catalyses the reaction is known as citrate synthase.

The mechanism shows the enol of acetyl CoA attacking the reactive ketone. In nature all these reactions are catalysed by the enzyme. In the C–C bond-forming step, one histidine residue removes the enol proton and another histidine, in its protonated form, is placed to donate a proton to the oxygen atom of the ketone. You should see now why histidine is so useful to enzymes: its imidazole ring means it can act either as an acid or as a base at neutral pH.

Even the hydrolysis of the reactive thiol ester is catalysed by the enzyme and histidine again functions as a proton donor, with the hydrolysis, like the enolization, being enhanced by the thiol ester. The two enol equivalents that we have met so far are quite general: lysine enamines can be used for any aldehyde or ketone and CoA thiol esters for any ester. Another class of enol equivalent—the enol ester—has just one representative but it is a most important one.

اخر الاخبار

اخبار العتبة العباسية المقدسة

خدمات فكرية وثقافية عديدة قدمها مركز مُلتقى القمر الثقافي لزائري الأربعين

إحياءً لذكرى زيارة الأربعين.. العتبة العباسية المقدسة تواصل إقامة مجلسها العزائي

عبر كاميرات تعمل بالذكاء الاصطناعي.. قسم الاتصالات يوضح تفاصيل جديدة حول آلية عدِّ زائري الأربعين

شعبة الخطابة الحسينية النسوية تواصل نشاطاتها الفكرية والثقافية في مجمع الشيخ الكليني

المزيد

الآخبار الصحية

حجم جزء محدد من الجسم يعكس الصحة العامة ومخاطر الأمراض

تفشي عدوى بكتيرية بفرنسا يحتمل ارتباطها بنوع من الجبن الطري

دراسة حديثة تكشف ما تفعله الشاشات بـ"قلوب الأطفال" !

متلازمة المبنى المريض.. هكذا يتحول تكييف الهواء إلى خطر صحي ؟؟

المزيد

الآخبار التكنلوجية

كيف تتعامل مع حرارة الطقس أثناء القيادة؟

لماذا يجب عليك إيقاف تكييف السيارة قبل إطفاء المحرك؟

دراسة تكشف سببا محتملا وراء زيادة خطر إصابة الأطفال بالتوحد

تشيلي.. العثور على متحجرة حيوان ثديي صغير من زمن الديناصورات

المزيد

مواضيع ذات صلة

Pyrrolidine alkaloids are made from the amino acid ornithine

Alkaloids are made by amino acid metabolism

The shikimic acid pathway

Phosphoenolpyruvate

Reductive amination in nature

Nature’s NaBH4 is a nucleotide: NADH or NADPH

Oil and water do not mix

Lipids

Most sugars are embedded in complex carbohydrates

Glycosides in nature

Sugars can be fixed in one shape by acetal formation

Sugars normally exist in cyclic forms with much stereochemistry