#malonyl CoA

[er-cryptid]

Fatty Acid Synthesis

-- most cells synthesize fatty acids

-- highest levels of synthesis occur in the -> liver -> adipose tissue

-- biosynthetic pathway is in cytosol

-- three-carbon intermediate = malonyl-CoA

-- energy expensive process

-- highly regulated

-- reaction: 8 acetyl-CoA + 14 NADPH + 7 ATP + 14 H⁺ -> palmitate + 14 NADP⁺ + 8 CoA + 7 ADP + 7 Pi + 6 H2O

.

Patreon

[leedsomics]

Comparative omics reveals unanticipated metabolic rearrangements in a high-oil mutant of plastid acetyl-CoA carboxylase

Heteromeric acetyl-CoA carboxylase (ACCase) catalyzes the ATP-dependent carboxylation of acetyl-CoA to produce malonyl-CoA, the committed step for de novo fatty acid synthesis. In plants, ACCase activity is controlled at multiple levels, including negative regulation by biotin attachment domain-containing (BADC) proteins, of which the badc1/3 double mutant leads to increased seed triacylglycerol accumulation. Unexpectedly, the Arabidopsis badc1/3 mutant also accumulates more protein. The metabolic consequences from both higher oil and protein was investigated in developing badc1/3 seed using global transcriptomics, translatomics, proteomics, and metabolomics. Changes include: reduced plastid pyruvate dehydrogenase; increased acetyl-CoA synthetase; increased storage and lipid-droplet packaging proteins; increased lipases; and increased {beta}-oxidation fatty acid catabolism. We present a model of how Arabidopsis adapted to deregulated ACCase, limiting total oil accumulation, and altering flux through pathways of carbon accumulation that presents possible targets for future bioengineering of valuable seed storage reserves. http://dlvr.it/SvVjw0

[ultrabellasmith55things-blog]

acaca

Acetyl-CoA carboxylase (ACC) is a complex multifunctional enzyme system. ACC is a biotin-containing enzyme which catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the rate-limiting step in fatty acid synthesis. There are two ACC forms, alpha and beta, encoded by two different genes. ACC-alpha is highly enriched in lipogenic tissues. 

[whats-in-a-sentence]

The malonyl-CoA then reacts with ACP to yield malonyl-ACP in the following four steps:

In the first cycle of fatty acid synthesis, the acetate group from acetyl-CoA is transferred to a specific cysteine of condensing enzyme (3-ketoacyl-ACP synthase) and then combined with malonyl-ACP to form acetoacetyl-ACP.

Next the keto group at carbon 3 is removed (reduced) by the action of three enzymes to form a new acyl chain (butyryl-ACP), which is now four carbons long (see Figure 12.17).

The four-carbon fatty acid and another molecule of malonyl-ACP then become the new substrates for condensing enzyme, resulting in the addition of another two-carbon unit to the growing chain. The cycle continues until 16 or 18 carbons have been added.

Some 16:0-ACP is released from the fatty acid synthesis machinery, but most molecules that are elongated to 18:0-ACP are efficiently converted into 18:1-ACP by a desaturase enzyme. Thus, 16:0-ACP and 18:1-ACP are the major products of fatty acid synthesis in plastids (Figure 12.18).

"Plant Physiology and Development" int'l 6e - Taiz, L., Zeiger, E., Møller, I.M., Murphy, A.

[moleculardepot]

Malonyl Coenzyme A

Malonyl Coenzyme A Catalog number: B2012921 Lot number: Batch Dependent Expiration Date: Batch dependent Amount: 1 mg Molecular Weight or Concentration: 860.5 g/mol Supplied as: Lyophilized Powder Applications: molecular tool for various biochemical applications Storage: -20°C Keywords: Malonyl-CoA Grade: Biotechnology grade. All products are highly pure. All solutions are made with Type I…

[eliasahmed1]

HVA ER QUERCETIN – ET BRA KOSTTILSKUDD?

Quercetin is a plant flavanol from the flavonoid gathering of polyphenols. It is tracked down in many natural products, vegetables, leaves, seeds, and grains; tricks,

From Wikipedia, the free reference book

UV apparent range of quercetin, with lambda max at 369 nm

Quercetin is a plant flavanol from the flavonoid gathering of polyphenols. It is tracked down in many natural products, vegetables, leaves, seeds, and grains; tricks, red onions, and kale are normal food sources containing obvious measures of it.[2][3] It tastes unpleasant and is utilized as a fixing in dietary enhancements, refreshments, and food varieties.

Quercetin is a flavonoid broadly conveyed in nature.[2] The name has been utilized beginning around 1857, and is gotten from quercetum (oak woodland), after the oak class Quercus.[4][5] It is a normally happening polar auxin transport inhibitor.[6]

Quercetin is one of the most plentiful dietary flavonoids,[2][3] with a typical everyday utilization of 25-50 milligrams.[7]

In red onions, higher convergences of quercetin happen in the peripheral rings and in the part nearest to the root, the last option being the piece of the plant with the most noteworthy concentration.[8] One investigation discovered that naturally developed tomatoes had 79% more quercetin than non-naturally developed fruit.[9] Quercetin is available in different sorts of honey from various plant sources.[10]

In plants, phenylalanine is switched over completely to 4-coumaroyl-CoA in a progression of steps known as the general phenylpropanoid pathway utilizing phenylalanine smelling salts lyase, cinnamate-4-hydroxylase, and 4-coumaroyl-CoA-ligase.[11] One particle of 4-coumaroyl-CoA is added to three particles of malonyl-CoA to frame tetrahydroxychalcone utilizing 7,2′-dihydroxy-4′-methoxyisoflavanol synthase. Tetrahydroxychalcone is then changed over into naringenin utilizing chalcone isomerase.

Naringenin is changed over into eriodictyol utilizing flavanoid 3′-hydroxylase. Eriodictyol is then changed over into dihydroquercetin with flavanone 3-hydroxylase, which is then changed over into quercetin utilizing flavonol synthase.[11]

3-O-Glycosides of quercetin

Quercetin is the aglycone type of various other flavonoid glycosides, for example, rutin (otherwise called quercetin-3-O-rutinoside) and quercitrin, found in citrus natural product, buckwheat and onions.[2] Quercetin structures the glycosides quercitrin and rutin along with rhamnose and rutinose, separately. Similarly guaijaverin is the 3-O-arabinoside, hyperoside is the 3-O-galactoside, isoquercitin is the 3-O-glucoside and spiraeoside is the 4′-O-glucoside. CTN-986 is a quercetin subordinate found in cottonseeds and cottonseed oil. Miquelianin is the quercetin 3-O-β-D-glucuronopyranoside.[12]

Various taxifolin (otherwise called dihydroquercetin) glycosides additionally exists.

Isoquercetin is the 3-O-glucoside of quercetin.

The protein quercitrinase can be found in Aspergillus flavus.[13] This chemical hydrolyzes the glycoside quercitrin to deliver quercetin and L-rhamnose. It is a catalyst in the rutin catabolic pathway.[14]

The bioavailability of quercetin in people after oral admission is exceptionally low, with one review closing it should be under 1%.[15] Intravenous infusion of quercetin shows a quick rot in focus portrayed by a two-compartment model (starting half-existence of 8.8 minutes, terminal half-existence of 2.4 hours).[15] In light of the fact that it goes through fast and broad digestion, the organic impacts assumed from in vitro examinations are probably not going to apply in vivo.[2][16][17][18] Quercetin supplements in the aglycone structure are less bioavailable than the quercetin glycoside frequently found in food varieties, particularly red onions.[2][19] Ingestion with high-fat food sources might increment bioavailability contrasted with ingestion with low-fat foods,[19] and carb rich food varieties might expand retention of quercetin by invigorating gastrointestinal motility and colonic fermentation.[2]

Quercetin is quickly processed (by means of glucuronidation) after the ingestion of quercetin food varieties or supplements.[20] Five metabolites (quercetin glucuronides) have been tracked down in human plasma after quercetin ingestion.[21][20] Taken together, the quercetin glucuronides have a half-life around 11-12 hours.[20]

In rodents, quercetin went through no huge stage I metabolism.[22] conversely, quercetin went through broad stage II (formation) to create metabolites that are more polar than the parent substance and consequently are all the more quickly discharged from the body. In vitro, the meta-hydroxyl gathering of catechol is methylated by catechol-O-methyltransferase. Four of the five hydroxyl gatherings of quercetin are glucuronidated by UDP-glucuronosyltransferase. The special case is the 5-hydroxyl gathering of the flavonoid ring which by and large doesn't go through glucuronidation. The significant metabolites of orally retained quercetin will be quercetin-3-glucuronide, 3'- methylquercetin-3-glucuronide, and quercetin-3'- sulfate.[22] A methyl metabolite of quercetin has been demonstrated in vitro to be more compelling than quercetin at restraining lipopolysaccharide-enacted macrophages.[18]

Contrasted with different flavonoids quercetin is one of the best inducers of the stage II detoxification enzymes.[23]

In-vitro examinations show that quercetin is areas of strength for an of the cytochrome P450 proteins CYP3A4 and CYP2C19 and a moderate inhibitor of CYP2D6.[24][25] Medications that are used by these pathways might make expanded difference. An in-vivo investigation discovered that quercetin supplementation eases back the digestion of caffeine to a genuinely critical degree in a specific hereditary sub-populace, yet in outright terms the impact was nearly negligible.[26]

Quercetin has been accounted for to hinder the oxidation of different particles and subsequently is delegated a cell reinforcement in vitro.[16] It contains a polyphenolic synthetic base that stops oxidation in vitro by going about as a scrounger of free revolutionaries. Quercetin has been displayed to restrain the PI3K/AKT pathway prompting downregulation of the counter apoptotic protein Bcl-w.[27][28] Quercetin enacts or hinders the exercises of various proteins in vitro. For instance, it is a vague protein kinase catalyst inhibitor.[16]

In 2010, the FDA recognized high-immaculateness quercetin as GRAS for use as a fixing in different determined food classes at levels up to 500 milligrams for each serving.[29]

Quercetin has been concentrated on in fundamental exploration and little clinical trials.[2][30][31][32] While supplements have been advanced for the therapy of malignant growth and different other diseases,[2][33] there is no great proof that quercetin (by means of enhancements or in food) is helpful to treat cancer [34] or some other disease.[2][35]

The US Food and Medication Organization has given cautioning letters to a few makers promoting on their item marks and sites that quercetin product(s) can be utilized to treat diseases.[36][37] The FDA respects such quercetin publicizing and items as unapproved - with unapproved wellbeing claims concerning the counter infection items - as characterized by "segments 201(g)(1)(B) or potentially 201 (g)(1)(C) of the Demonstration [21 U.S.C. § 321(g)(1)(B) and additionally 21 U.S.C. § 321(g)(1)(C)] in light of the fact that they are planned for use in the conclusion, fix, moderation, treatment, or anticipation of disease",[36][37] conditions not met by the producers.

There has been little examination into the wellbeing of quercetin supplementation in people, and the outcomes are lacking to give certainty that the training is protected. Specifically, there is an absence of security data on the impact of quercetin supplementation for pregnant ladies, breastfeeding ladies, kids, and teenagers. The hormonal impacts of quercetin found in creature concentrates on raise the doubt of an equal impact in people, especially in regard of estrogen-subordinate tumors.[38]

Quercetin supplementation can impede the impacts of meds. The exact idea of this association is known for a few normal meds, yet for some, it is not.[38]

[collegeandknowledge]

Under high energy balance, your acetyl-CoA is being carboxylated to malonyl CoA, and this inhibits fatty acid transportation into the mitochondria. Under low energy balance, the opposite effect is happening (more fatty acid is oxidized in the mitochondria to produce ATP). Insulin is a key regulator of this mechanism.

[mcatmemoranda]

[whats-in-a-sentence]

The first committed step in the pathway (i.e., the first step unique to the synthesis of fatty acids) is the synthesis of malonyl-CoA from acetyl-CoA and CO2 by the enzyme acetyl-CoA carboxylase (Figure 12.17).

"Plant Physiology and Development" int'l 6e - Taiz, L., Zeiger, E., Møller, I.M., Murphy, A.

[physiologyopen]

Insulin function physiology | Endocrine physiology

The main function of insulin is to store the excess fuel during times of their availability for future use. Thus insulin is released in the fed state when the availability of the fuel especially carbohydrates is high. As these substrates are absorbed from gastrointestinal tract, their concentration in blood rises. However, with the release of the insulin, they are quickly moved from the blood into their storage depots. So how does insulin promote the storage of nutrients ? By affecting the entry of nutrients into cells and their metabolic cycles. 

Factors which cause increase in blood glucose concentration are 

1. Intake of food and digestion and absorption of nutrients into the blood stream 

2. Glycogenolysis 

3. Gluconeogenesis: Causes synthesis of new glucose mainly from amino acids  

Insulin inhibits Glycogenolysis and Gluconeogenesis 

 Factors which cause decrease in blood glucose concentration are: 

 1. Glycogenesis which occurs mainly in liver and skeletal muscles 

2. Storage of excess glucose as fatty acids.. this also occurs in liver 

3. Utilization of glucose by peripheral tissues Insulin promotes the factors which cause decrease in blood glucose concentration 

 Similarly for fats and proteins, concentration is increased by lipolysis and proteolysis respectively and decreased by promoting their entry into cells and causing fatty acid synthesis and protein synthesis respectively. 

Insulin promotes the synthetic pathways and inhibits the lytic pathways 

 The actions of insulin occur  mainly in 3 tissues, liver, skeletal muscles and adipose tissue 

 Liver

 In liver it increases the activity of enzyme glucokinase which converts glucose to glucose 6 phosphate.  Then it promotes glycogenesis by increasing the activity of glycogen synthase while it inhibits glycogenolysis by inhibiting glycogen phosphorylase. Also, excess glucose which has not been converted into glycogen enters into glycolysis pathway and produces acetyl CoA in liver. Now this acetylCoA  is used for synthesis of fatty acids since insulin promotes the activity of the enzyme Acetyl CoA carboxylase . Also, in the process of synthesis of fatty acids, malonyl CoA is formed which inhibits carnitine palmitoyltransferase enzyme and hence inhibits beta oxidationof fatty acids.  The formed fatty acids should now go and get stored in their depots i.e adipose tissue. So they are transported from liver to adipose tissue as triacylcglycerols in VLDL via blood…Insulin increases the expression of lipoprotein lipase in the walls of capillaries of adipose tissue. This lipoprotein lipase releases fatty acids from triacylglycerols in VLDL which then enter into the adipose tissue. 

 Skeletal muscles: 

 Insulin also promotes the entry of glucose in most cells except neurons and RBCs. It does this, by causing fusion of GLUT 4 transporters which are present inside the cell to the membrane. This increases their number on the membrane. Since glucose is in higher concentration in blood, it enters into the cells along its concentration gradient via these GLUT 4 transporters by facilitated diffusion. So most cells start using glucose as a fuel in presence of insulin and hence usage of fats as fuel is spared.  In skeletal muscles, excess glucose is also stored as glycogen .. 

 Adipose tissue: 

The glucose acts as a substrate for glycerol portion of triacylglycerol in adipose tissue. So the glycerol and fatty acids combine to form triacylglycerol in adipose tissue. Also insulin  inhibits hormone sensitive lipase in fat cells. This lipase breaks down stored triacylglycerol into fatty acids and glycerol. Thus by inhibiting hormone sensitive lipase, insulin prevents hydrolysis of triglycerides in adipose tissue. 

 Effects on protein metabolism: Insulin also promotes amino acid uptake by cells and promotes protein synthesis, simultaneously inhibiting their breakdown.

[you-cancer-vive]

OVERVIEW OF LIPID METABOLISM

After digestion, dietary lipids are converted to two free fatty acids and MAGs (monoacylglycerol), which is then reesterified as TAGs. They are then carried out by chylomicrons. It is important to note that TAGs cannot be stored in the liver. Thus, they are exported out as VLDL. Both chylomicrons and VLDL will be acted upon lipoprotein lipase, found in the linings of blood vessels. 

The end products of lipid metabolism are glycerol and 3 free fatty acids. The major precursor for TAG synthesis anywhere in the body is glucose via glycolysis or glycerol phosphate kinase, and not dietary TAGs. In the fed state, glycerol goes back to the liver and is converted to DHAP as it enters glycolysis, becoming a precursor for TAGs. Glycerol cannot be used as a precursor of TAGs in the adipocytes because they do not have the enzyme glycerol kinase. Citrate is formed by the condensation of oxaloacetate and acetyl CoA by citrate synthase in the mitochondria (the first reaction of TCA). Citrate then goes out from the mitochondria into the cytosol via citrate lyase, resulting to Acetyl CoA. This is then used as a precursor for palmitate or fatty acid synthesis.

LIPOGENESIS

Lipogenesis is the process of sequentially combining two carbon fragments (acetyl group from Acetyl-CoA) to the activated carboxyl end of a chain in 8 cycles forming 16-Carbon saturated fatty acid, Palmitate. Its immediate substrate and precursor is Acetyl-CoA from glucose metabolism and end product is Palmitate (16:0), which is the most common product of fatty acid synthesis and most common substrate for elongation and desaturation. The site of TAG synthesis is in the liver, specifically the cytosol. The rate-limiting step of the process is the conversion of Acetyl-CoA to Malonyl-CoA, a 3-Carbon subunit and donor of 2-Carbon chain for fatty acid elongation. The rate-limiting enzyme during this step is the Acetyl-CoA Carboxylase (ACC1). The main reducing agent is NADPH from Pentose Phosphate Pathway and recycling of OAA produced by citrate lyase.

References:

Smith, C. M., Marks, A. D., Lieberman, M. A., Marks, D. B., & Marks, D. B. (2005). Marks' basic medical biochemistry: A clinical approach. Philadelphia: Lippincott Williams & Wilkins.

 Devlin, T. 2011. Textbook of Biochemistry with Clinical Correlations. John Wiley & Sons, Inc.

[rnomics]

Microorganisms, Vol. 8, Pages 271: Regulatory Patterns of Crp on Monensin Biosynthesis in Streptomyces cinnamonensis

Monensin, produced by Streptomyces cinnamonensis, is a polyether ionophore antibiotic widely used as a coccidiostat and a growth-promoting agent in agricultural industry. In this study, cyclic AMP receptor protein (Crp), the global transcription factor for regulation of monensin biosynthesis, was deciphered. The overexpression and antisense #RNA silencing of crp revealed that Crp plays a positive role in monensin biosynthesis. #RNA sequencing analysis indicated that Crp exhibited extensive regulatory effects on genes involved in both primary metabolic pathways and the monensin biosynthetic gene cluster (mon). The primary metabolic genes, including acs, pckA, accB, acdH, atoB, mutB, epi and ccr, which are pivotal in the biosynthesis of monensin precursors malonyl-CoA, methylmalonyl-CoA and ethylmalonyl-CoA, are transcriptionally upregulated by Crp. Furthermore, Crp upregulates the expression of most mon genes, including all PKS genes (monAI to monAVIII), tailoring genes (monBI-monBII-monCI, monD and monAX) and a pathway-specific regulatory gene (monRI). Enhanced precursor supply and the upregulated expression of mon cluser by Crp would allow the higher production of monensin in S. cinnamonensis. This study gives a more comprehensive understanding of the global regulator Crp and extends the knowledge of Crp regulatory mechanism in Streptomyces. http://bit.ly/2UXZRRI

[dorcasrempel]

A new way to control microbial metabolism

Microbes can be engineered to produce a variety of useful compounds, including plastics, biofuels, and pharmaceuticals. However, in many cases, these products compete with the metabolic pathways that the cells need to fuel themselves and grow.

To help optimize cells’ ability to produce desired compounds but also maintain their own growth, MIT chemical engineers have devised a way to induce bacteria to switch between different metabolic pathways at different times. These switches are programmed into the cells and are triggered by changes in population density, with no need for human intervention.

“What we’re hoping is that this would allow more precise regulation of metabolism, to allow us to get higher productivity, but in a way where we minimize the number of interventions,” says Kristala Prather, the Arthur D. Little Professor of Chemical Engineering and the senior author of the study.

This kind of switching allowed the researchers to boost the microbial yields of two different products by up to tenfold.

MIT graduate student Christina Dinh is the lead author of the paper, which appears in the Proceedings of the National Academy of Sciences this week.

Double switch

To make microbes synthesize useful compounds that they don’t normally produce, engineers insert genes for enzymes involved in the metabolic pathway — a chain of reactions that generate a specific product. This approach is now used to produce many complex products, such as pharmaceuticals and biofuels.

In some cases, intermediates produced during these reactions are also part of metabolic pathways that already exist in the cells. When cells divert these intermediates out of the engineered pathway, it lowers the overall yield of the end product.

Using a concept called dynamic metabolic engineering, Prather has previously built switches that help cells maintain the balance between their own metabolic needs and the pathway that produces the desired product. Her idea was to program the cells to autonomously switch between pathways, without the need for any intervention by the person operating the fermenter where the reactions take place.

In a study published in 2017, Prather’s lab used this approach to program E. coli to produce glucaric acid, a precursor to products such as nylons and detergents. The researchers’ strategy was based on quorum sensing, a phenomenon that bacterial cells normally use to communicate with each other. Each species of bacteria secretes particular molecules that help them sense nearby microbes and influence each other’s behavior.

The MIT team engineered their E. coli cells to secrete a quorum sensing molecule called AHL. When AHL concentrations reach a certain level, the cells shut off an enzyme that diverts a glucaric acid precursor into one of the cells’ own metabolic pathways. This allows the cells to grow and divide normally until the population is large enough to start producing large quantities of the desired product.

“That paper was the first to demonstrate that we could do autonomous control,” Prather says. “We could start the cultures going, and the cells would then sense when the time was right to make a change.”

In the new PNAS paper, Prather and Dinh set out to engineer multiple switching points into their cells, giving them a greater degree of control over the production process. To achieve that, they used two quorum sensing systems from two different species of bacteria. They incorporated these systems into E. coli that were engineered to produce a compound called naringenin, a flavonoid that is naturally found in citrus fruits and has a variety of beneficial health effects.

Using these quorum sensing systems, the researchers engineered two switching points into the cells. One switch was designed to prevent bacteria from diverting a naringenin precursor called malonyl-CoA into the cells’ own metabolic pathways. At the other switching point, the researchers delayed production of an enzyme in their engineered pathway, to avoid accumulating a precursor that normally inhibits the naringenin pathway if too much of the precursor accumulates.

“Since we took components from two different quorum sensing systems, and the regulator proteins are unique between the two systems, we can shift the switching time of each of the circuits independently,” Dinh says.

The researchers created hundreds of E. coli variants that perform these two switches at different population densities, allowing them to identify which one was the most productive. The best-performing strain showed a tenfold increase in naringenin yield over strains that didn’t have these control switches built in.

More complex pathways

The researchers also demonstrated that the multiple-switch approach could be used to double E. coli production of salicylic acid, a building block of many drugs. This process could also help improve yields for any other type of product where the cells have to balance between using intermediates for product formation or their own growth, Prather says. The researchers have not yet demonstrated that their method works on an industrial scale, but they are working on expanding the approach to more complex pathways and hope to test it at a larger scale in the future.

“We think it certainly has broader applicability,” Prather says. “The process is very robust because it doesn’t require someone to be present at a particular point in time to add something or make any sort of adjustment to the process, but rather allows the cells to be keeping track internally of when it’s time to make a shift.”

The research was funded by the National Science Foundation.

A new way to control microbial metabolism syndicated from https://osmowaterfilters.blogspot.com/

[tuohuozu-blog]

Biosynthesis of Olivetol

Olivetol is biosynthesized by a polyketide synthase-type reaction from hexanoyl-CoA and three molecules of malonyl-CoA by an aldol condensation of a tetraketide intermediate. In 2009, Taura et al. was able to clone a type III PKS named olivetol synthase (OLS) from Cannabis sativa.This PKS is a homodimeric protein that consists of a 385 amino acid polypeptide with a molecular mass of 42,585 Da that has high sequence similarity (60-70%) identity to plant PKS's. The data from Taura's study of OLS's enzyme kinetics show that OLS catalyzes a decarboxylative-aldol condensation to produce olivetol. This is similar to stilbene synthase’s (STS) mechanism for converting p-coumaroyl-CoA and malonyl-CoA to resveratrol. Although olivetol is the decarboxylated form of OLA, it is highly unlikely that OLS produces olivetol from OLA.Crude enzyme extracts prepared from flowers and leaves did not synthesize olivetolic acid, but only yielded olivetol.The exact mechanism of olivetol biosynthesis is as yet unsure, but it is possible that an OLA-forming metabolic complex forms along with OLS.In addition, it also appears that OLS only specifically accepts starter CoA esters with C4 to C8 aliphatic side chains such as hexanoyl-CoA.  

[speedessays]

Pure Preparation of the Enzyme that Catalyzes Palmitate Synthesis

Pure Preparation of the Enzyme that Catalyzes Palmitate Synthesis

Pure Preparation of the Enzyme that Catalyzes Palmitate Synthesis

The following experiments are carried out using a pure preparation of the enzyme that catalyzes palmitate synthesis from acetyl CoA and malonyl CoA in the presence of all the cofactors required for reaction.

a) If the acetyl CoA is labeled at the methyl carbon with tritium, and malonyl CoA is unlabeled, how many tritium atoms will…

[bookpiofficial]

Randle Cycle as Applied to Diabetes Mellitus Type 2 ‘Spruce the Basement before Dusting the Super-structure’| Chapter 2 | Modern Advances in Pharmaceutical Research Vol. 1

Randle cycle (1963) is about substrate competition between products of glycolysis and β–oxidation to capture the citric acid cycle for further oxidation. Acetyl –CoA, the end product of both the energy metabolisms, when accumulates in mitochondrial matrix beyond the oxidative capacity of the citric acid cycle, far-reaching consequences take place than simple substrate competition, inhibition of pyruvate dehydrogenase (PDH), inhibition  of  glycolysis and  preferential  passage of  β-oxidation products through citric acid cycle, as conceived by Randle. It is shown that citric acid cycle is equally shut off for both products of energy metabolism initially. Hence, the question of substrate competition between them  does  not arise.  How  the preferential  passage  of β-oxidation  products  occurs is explained by a different mechanism than what Randle put forward. The final common pathway to either of β-oxidation or lipogenesis is- acetyl CoA carboxylase (ACC)-malonyl- CoA-CPT 1. The final result depends on whether ACC is stimulated or inhibited. Inhibition of ACC results in β-oxidation and stimulation results in lipogenesis. Randle’s  contention that the low ATP status due to substrate  competitive inhibition , stimulates AMPK ,which results in initiation and perpetuation of β -oxidation   is not true because, simultaneously, AMPK is also inhibited which inhibits, in turn, the β -oxidation The proposed  hypothesis  suggests that  low  substrate for  ACC  i.e. Plasma  acetyl- CoA,  which is carboxylated  to  malonyl- CoA is  responsible  for the  switch  of energy  metabolism  to β-oxidation independent of AMPK. To corroborate the proposed mechanism, a low pyruvate level, an additional block in the glycolytic pathway at the  level of Pyruvate kinase (PK) and involvement of hexose monophosphate shunt (HMP shunt) are proposed with objective evidence, supporting the same.

Author(s) Details

A. S. V. Prasad Department of Internal Medicine, G.I.T.A.M Dental College, Rushikonda, Visakhapatnam, Andhra Pradesh, India.

Read full article: http://bp.bookpi.org/index.php/bpi/catalog/view/47/230/395-1

View Volume: https://doi.org/10.9734/bpi/mapr/v1