Kegg Pathway: Synthesis and degradation of ketone bodies

KEGG ID: 00072

Reference Diagram

KEGG Diagram for Synthesis and degradation of ketone bodies

Rat

There are 5 IPI Records from this pathway found in Rattus norvegicus.

Location of Synthesis and degradation of ketone bodies proteins on Rat Genome

IPI Record Position
1: Acat1 8:57044707-57072970
2: Bdh1 11:71130561-71165695
3: Hmgcl 5:154730230-154743974
4: Hmgcs1 2:51737090-51754583
5: Hmgcs2 2:193128730-193143109

Mouse

There are 5 IPI Records from this pathway found in Mus musculus.

Location of Synthesis and degradation of ketone bodies proteins on Mouse Genome

IPI Record Position
1: Acat1 9:53342917-53372745
2: Acat2 17:12786794-12803595
3: Bdh1 16:31342041-31377244
4: Hmgcl 4:135218541-135234684
5: Hmgcs1 :-
6: Hmgcs2 3:98365840-98396137
7: Oxct1 15:3976428-4103962
8: Oxct2a 4:122824178-122825937

Human

There are 5 IPI Records from this pathway found in Homo sapiens.

Location of Synthesis and degradation of ketone bodies proteins on Human Genome

IPI Record Position
1: ACAT1 11:107497468-107523485
2: ACAT2 6:160101350-160120077
3: BDH1 3:198721051-198784591
4: BDH2 4:104218232-104240473
5: HMGCL 1:24000909-24025264
6: HMGCS1 5:43325255-43349241
7: HMGCS2 1:120092142-120113040
8: OXCT1 5:41765924-41906360
9: OXCT2 1:40007782-40009607

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Recent Literature

Cellular expression of a sodium-dependent monocarboxylate transporter (Slc5a8) and the MCT family in the mouse kidney.

Histochem Cell Biol. 2008 Aug 27;
Yanase H, Takebe K, Nio-Kobayashi J, Takahashi-Iwanaga H, Iwanaga T

Expression analysis of transporters selective for monocarboxylates such as lactate and ketone bodies in the kidney contributes to understanding the renal energy metabolism. Distribution and expression intensity of a sodium-dependent monocarboxylate transporter (SMCT) and proton-coupled monocarboxylate transporters (MCT) were examined in the mouse kidney. In situ hybridization survey detected significant mRNA expressions of SMCT and MCT-1, 2, 5, 8, 9, 10, and 12. Among these, signals for SMCT, MCT2 and MCT8 were predominant; transcripts of SMCT were restricted to the cortex and the outer stripe of outer medulla, while those of MCT2 and MCT8 gathered in the inner stripe of outer medulla and the cortex, respectively. Immunohistochemically, SMCT was present at the brush border in S2 and S3 of proximal tubules, suggesting the active uptake of luminal monocarboxylates here. MCT1 and MCT2 immunoreactivities were respectively found baso-laterally in S1 and thick ascending limbs of Henle's loop. The cellular localization of transporters suggests the involvement of SMCT in the uptake of filtrated lactate and ketone bodies and that of MCTs in the transport of monocarboxylate metabolites between tubular cells and circulation, but the different distribution patterns do not support the notion of a functional linkage between SMCT and MCT1/MCT2.

Growth of children on classical and medium-chain triglyceride ketogenic diets.

Pediatrics. 2008 Aug; 122(2): e334-40
Neal EG, Chaffe HM, Edwards N, Lawson MS, Schwartz RH, Cross JH

OBJECTIVE: The objectives of this study were to examine growth in children on classical and medium-chain triglyceride ketogenic diets and to investigate any association between growth and calorie or protein intake. METHODS: Weight, height, and BMI z scores were recorded for children who were initiated on 1 of 2 ketogenic diets at baseline and after 3, 6, and 12 months, if continued. Mean calorie and protein intakes during treatment were calculated for children who completed 12 months on the diet. Changes in growth were compared between the 2 diets, and the association between growth and dietary intake was examined. RESULTS: Seventy-five children provided growth data. Weight z scores decreased significantly between baseline and 3, 6, and 12 months; height z scores showed no change at 3 months but decreased significantly by 6 and 12 months. This was more significant in the younger and ambulatory children. Subdivision according to diet type showed weight z scores to decrease significantly in the medium-chain triglyceride group only at 3 and 6 months and in both groups at 12 months. Height z scores decreased significantly in both groups by 6 and 12 months. Forty children completed 12 months of treatment; in this group, the slopes of best-fit regression lines of serial z-score measures were used to represent growth trend. There were no significant differences in mean slope between classical and medium-chain triglyceride diet groups for weight, height, or BMI. There was no significant difference in mean calorie intake during the 12 months between the 2 diets, but the medium-chain triglyceride group had significantly higher protein intake. There was no significant correlation between calorie or protein intakes and the slope of the best-fit line for weight, height, or BMI. CONCLUSIONS: Both weight and height z scores decreased during diet treatment. By 12 months, there was no difference in outcome between classical and medium-chain triglyceride protocols despite the increased protein in the latter diet.

Long-term outcome of the ketogenic diet for intractable childhood epilepsy with focal malformation of cortical development.

Pediatrics. 2008 Aug; 122(2): e330-3
Jung da E, Kang HC, Kim HD

OBJECTIVE: We evaluated the efficacy and long-term outcome of the ketogenic diet in patients with intractable childhood epilepsy as a result of focal malformation of cortical development. METHODS: A retrospective analysis evaluated seizure outcomes of 47 patients who had intractable epilepsy from (and) surgically remediable focal malformation of cortical development and were first treated with the classic ketogenic diet, involving the 4:1 lipid/nonlipid ratio. The long-term prognosis of 21 patients, who became seizure-free 3 months after the ketogenic diet, was followed up with that of 22 patients who eventually underwent epilepsy surgery. RESULTS: Three months after diet initiation, 29 (61.7%) patients showed a reduction in seizure frequency of >50%, including 21 (44.7%) who became seizure-free. Of the 21 patients with complete seizure control at 3 months, 16 (76.2%) successfully completed the diet for 2 years without relapse, and 10 (47.6%) have remained seizure-free after cessation of the diet (mean follow-up for 3 years and 10 months), including 1 patient who remained seizure-free with additional medication after a relapse. Of the 22 patients who underwent epilepsy surgery, a seizure-free outcome was obtained for 13 (59.1%). CONCLUSIONS: The ketogenic diet should be considered to be an additional option even in patients with focal malformation of cortical development, and long-term seizure-free outcome can be expected for patients who become seizure-free 3 months after the diet.

The SLC16 monocaboxylate transporter family.

Xenobiotica. 2008 Jul; 38(7): 1072-106
Meredith D, Christian HC

1. The monocarboxylate transporter (MCT, SLC16) family comprises 14 members, of which to date only MCT1-4 have been shown to carry monocarboxylates, transporting important metabolic compounds such as lactate, pyruvate and ketone bodies in a proton-coupled manner. The transport of such compounds is fundamental for metabolism, and the tissue locations, properties and regulation of these isoforms is discussed. 2. Of the other members of the MCT family, MCT8 (a thyroid hormone transporter) and TAT1 (an aromatic amino acid transporter) have been characterized more recently, and their physiological roles are reviewed herein. The endogenous substrates and functions of the remaining members of the MCT family await elucidation. 3. The MCT proteins have the typical twelve transmembrane-spanning domain (TMD) topology of membrane transporter proteins, and their structure-function relationship is discussed, especially in relation to the future impact of the single nucleotide polymorphism (SNP) databases and, given their ability to transport pharmacologically relevant compounds, the potential impact for pharmacogenomics.

Liver-specific silencing of the human gene encoding succinyl-CoA: 3-ketoacid CoA transferase.

Tohoku J Exp Med. 2008 Jul; 215(3): 227-36
Orii KE, Fukao T, Song XQ, Mitchell GA, Kondo N

The human succinyl-CoA: 3-ketoacid CoA transferase (SCOT) gene encodes the ketolytic enzyme that functions in the mitochondrial matrix. The activation of acetoacetate to acetoacetyl-CoA by SCOT is essential for the use of ketone bodies as an energy source. The ketolytic capacity of tissues is proportional to their level of SCOT activity. Normal hepatocytes, the site of ketone body Synthesis, have no detectable SCOT protein. The absence of SCOT in hepatocytes is an important element in energy metabolism, suppressing ketolysis in the liver. To study the tissue-specific silencing of SCOT expression, we analyzed the promoter function of SCOT gene in three different human cell lines. Immunoblot analysis showed that SCOT protein was detectable in HeLa cervical cancer cells and Chang liver cells. However, SCOT protein was not detected in HepG2 hepatoma cells and liver tissues, indicating that HepG2 hepatoma cells maintain the characteristics of liver cells in the ketone body metabolism. Luciferase reporter assays in HeLa and Chang liver cells showed that the 361-bp proximal region of the SCOT gene was responsible for the basal promoter activity and contained two GC boxes, each of which was bound in vitro by Sp1, a ubiquitously expressed transcription factor. These results suggest that these GC boxes may be important for SCOT gene expression. Moreover, the region between -2168 and -361 appeared to inhibit the SCOT promoter activity in HepG2 cells. Thus, liver-specific silencing of the SCOT gene expression may be mediated in part by its 5'-flanking sequence.

[Physiological functions of carnitine and carnitine transporters in the central nervous system]

Nihon Shinkei Seishin Yakurigaku Zasshi. 2008 Jun; 28(3): 113-20
Inazu M, Matsumiya T

L-Carnitine is an essential co-factor in the metabolism of lipids and consequently in the production of cellular energy. This molecule has important physiological roles, including its involvement in the beta-oxidation of fatty acids by facilitating the transport of long-chain fatty acids across the mitochondrial inner membrane as acylcarnitine esters. In the brain, L-carnitine and acetyl-L-carnitine have important roles in cerebral bioenergetics and in neuroprotection through a variety of mechanisms including their antioxidant properties and in the modulation and promotion of synaptic neurotransmission, most notably cholinergic neurotransmission. Acetyl-L-carnitine was successfully applied as pharmacological agents for treatment of chronic degenerative diseases of the senile brain and for slowing down the progression of mental deterioration in Alzheimer's disease, and they may involve both the cholinergic neuronal transmission activity of acetyl-L-carnitine and its ability to enhance neuronal metabolism in mitochondria. Astrocytes are able to produce large amounts of ketone bodies, which are thought to supply adjacent neurons with easily transferable substrates for generation of energy. Thus, the L-carnitine uptake mechanism becomes the rate-limiting step for astrocyte ketogenesis. Several carnitine transporters have been known to be present in peripheral tissues. In this review, the functional expression and physiological role of carnitine transporters in central nervous system is further discussed.

Cytochrome P450 polymorphism--molecular, metabolic, and pharmacogenetic aspects. II. Participation of CYP isoenzymes in the metabolism of endogenous substances and drugs.

Acta Pol Pharm. 2008 May-Jun; 65(3): 307-18
Tomaszewski P, Kubiak-Tomaszewska G, Pachecka J

In the human organism 58 cytochrome P450 (CYP) isoenzymes belonging to 18 families have been described. These hemoproteins, with enzymatic activity characteristic for monooxygenases, show a broad affinity for chemically differentiated endo- or exogenous compounds, including drugs. CYP isoenzymes participate in metabolic pathways important for proper physiological functioning of the human organism, i.e.: cholesterol, bile acid and oxysterol bioSynthesis; metabolism of fatty acids, prostaglandins, prostacyclins, leukotrienes, steroid hormones, ketone bodies, vitamines A and D. CYP isoenzymes participate in the metabolism of over 80% of drugs and other xenobiotic substances which can be present in the human organism. Differences in molecular structure and kinetics of conformational changes of particular isoenzymes of CYP superfamily monooxygenases on the one hand determine their affinity direction for chemically differentiated groups of compounds susceptible to oxidation, on the other hand determine the mechanism and position of the oxidative change of their molecules. Drugs and their metabolites and other endogenous and xenobiotic compounds may be acting not only as substrates, but also as competitive and non- competitive inhibitors, suicide inhibitors and inducers of CYP isoenzymes as well as repressors of CYP genes. These relationships are the metabolic basis of numerous multidirectional interactions between drugs, drug metabolites, food components, stimulants, environmental toxins and metabolites of these xenobiotics.

ketone bodies as a therapeutic for Alzheimer's disease.

Neurotherapeutics. 2008 Jul; 5(3): 470-80
Henderson ST

An early feature of Alzheimer's disease (AD) is region-specific declines in brain glucose metabolism. Unlike other tissues in the body, the brain does not efficiently metabolize fats; hence the adult human brain relies almost exclusively on glucose as an energy substrate. Therefore, inhibition of glucose metabolism can have profound effects on brain function. The hypometabolism seen in AD has recently attracted attention as a possible target for intervention in the disease process. One promising approach is to supplement the normal glucose supply of the brain with ketone bodies (KB), which include acetoacetate, beta-hydroxybutyrate, and acetone. KB are normally produced from fat stores when glucose supplies are limited, such as during prolonged fasting. KB have been induced both by direct infusion and by the administration of a high-fat, low-carbohydrate, low-protein, ketogenic diets. Both approaches have demonstrated efficacy in animal models of neurodegenerative disorders and in human clinical trials, including AD trials. Much of the benefit of KB can be attributed to their ability to increase mitochondrial efficiency and supplement the brain's normal reliance on glucose. Research into the therapeutic potential of KB and ketosis represents a promising new area of AD research.

Lipid, ketone body and oxidative metabolism in the African lungfish, Protopterus dolloi following 60 days of fasting and aestivation.

Comp Biochem Physiol A Mol Integr Physiol. 2008 Sep; 151(1): 93-101
Frick NT, Bystriansky JS, Ip YK, Chew SF, Ballantyne JS

The potential importance of lipids and ketone bodies as fuels in the African lungfish, Protopterus dolloi, and the role of oxidative metabolism, were examined under control, fasted and aestivated conditions. In aestivating but not fasting lungfish, the activities of citrate synthase (CS) and cytochrome c oxidase (CCO) (enzymes of oxidative metabolism) showed tissue-specific changes. Significant reductions in CS activity occurred in the kidney, heart, gill and muscle, and in CCO in the liver and kidney tissues. Aestivation, but not fasting, also had a tissue-specific effect on mitochondrial state 3 respiration rates (using succinate as a substrate), with a >50% reduction in the liver, yet no change within muscle mitochondria. There is no indication that enzymes involved in lipid catabolism are up-regulated during periods of fasting or aestivation; however, both 3-hydroxyacyl CoA dehydrogenase (HOAD) and carnitine palmitoyl CoA transferase (CPT) activities were sustained in the liver despite the approximately 42% reduction in CCO activity, potentially indicating lipid metabolism is of importance during aestivation. Lungfish are able to utilize both the d- and l-stereoisomers of the ketone body beta-hydroxybutyrate (beta-HB); however, beta-HB does not appear to be an important fuel source during aestivation or fasting as no changes were observed in beta-HB tissue levels. This study demonstrates that an important aspect of metabolic depression during aestivation in lungfish is the tissue-specific down regulation of enzymes of aerobic metabolism while maintaining the activities of enzymes in pathways that supply substrates for aerobic metabolism.

Induction of ketosis may improve mitochondrial function and decrease steady-state amyloid-beta precursor protein (APP) levels in the aged dog.

Brain Res. 2008 Aug 21; 1226: 209-17
Studzinski CM, Mackay WA, Beckett TL, Henderson ST, Murphy MP, Sullivan PG, Burnham WM

Region specific declines in the cerebral glucose metabolism are an early and progressive feature of Alzheimer's disease (AD). Such declines occur pre-symptomatically and offer a potential point of intervention in developing AD therapeutics. Medium chain triglycerides (MCTs), which are rapidly converted to ketone bodies, were tested for their ability to provide an alternate energy source to neurons suffering from compromised glucose metabolism. The present study determined the short-term effects of ketosis in aged dogs, a natural model of amyloidosis. The animals were administered a 2 g/kg/day dose of MCTs for 2 months. Mitochondrial function and oxidative damage assays were then conducted on the frontal and parietal lobes. Amyloid-beta (Abeta), amyloid precursor protein (APP) processing and beta-site APP cleaving enzyme (BACE1) assays were conducted on the frontal, parietal and occipital lobes. Aged dogs receiving MCTs, as compared to age-matched controls, showed dramatically improved mitochondrial function, as evidenced by increased active respiration rates. This effect was most prominent in the parietal lobe. The improved mitochondrial function may have been due to a decrease in oxidative damage, which was limited to the mitochondrial fraction. Steady-state APP levels were also decreased in the parietal lobe after short-term MCT administration. Finally, there was a trend towards a decrease in total Abeta levels in the parietal lobe. BACE1 levels remained unchanged. Combined, these findings suggest that short-term MCT administration improves energy metabolism and decreases APP levels in the aged dog brain.

Modeling, analysis, and validation of a novel HIV integrase structure provide insights into the binding modes of potent integrase inhibitors.

J Mol Biol. 2008 Jul 11; 380(3): 504-19
Chen X, Tsiang M, Yu F, Hung M, Jones GS, Zeynalzadegan A, Qi X, Jin H, Kim CU, Swaminathan S, Chen JM

It has been shown that L-731988, a potent integrase inhibitor, targets a conformation of the integrase enzyme formed when complexed to viral DNA, with the 3'-end dinucleotide already cleaved. It has also been shown that diketo acid inhibitors bind to the strand transfer complex of integrase and are competitive with the host target DNA. However, published X-ray structures of HIV integrase do not include the DNA; thus, there is a need to develop a model representing the strand transfer complex. In this study, we have constructed an active-site model of the HIV-1 integrase complexed with viral DNA using the crystal structure of DNA-bound transposase and have identified a binding mode for inhibitors. This proposed binding mechanism for integrase inhibitors involves interaction with a specific Mg(2+) in the active site, accentuated by a hydrophobic interaction in a cavity formed by a flexible loop upon DNA binding. We further validated the integrase active-site model by selectively mutating key residues predicted to play an important role in the binding of inhibitors. Thus, we have a binding model that is applicable to a wide range of potent integrase inhibitors and is consistent with the available resistant mutation data.

Influence of dynamic hand-grip exercise on acetone in gas emanating from human skin.

Redox Rep. 2008; 13(3): 139-42
Mori K, Funada T, Kikuchi M, Ohkuwa T, Itoh H, Yamazaki Y, Tsuda T

This study investigated the effects of dynamic hand-grip exercise on skin-gas acetone concentration. The subjects for this experiment were seven healthy males. In the first experiment, to ascertain the reproducibility of the results for the skin-gas acetone concentration test, the skin gas was collected four times from one subject. In the second experiment, all subjects performed three different types of exercise (Exercises I-III) for a duration of 60 s. Exercise I was performed at 10 kg with one contraction every 3 s. Exercise II was 30 kg with one contraction every 3 s. Exercise III was 10 kg with one contraction per second. Acetone concentration was analyzed by gas chromatography. In the first experiment, reasonable reproducibility was obtained in measurements of skin-gas acetone concentration during the hand-grip exercise. In the second experiment, acetone concentration in skin gas during hand-grip exercise II was significantly higher than the basal level. Although skin-gas acetone levels increased in all subjects during exercises I and III, a significant difference was not found. No significant difference was found in skin-gas acetone concentration during dynamic hand-grip exercise among exercises I, II, and III. This study confirmed that skin-gas acetone levels increase during dynamic hand-grip exercise.

In vitro and in vivo transdermal studies of atenolol using iontophoresis.

Acta Pol Pharm. 2008 Jan-Feb; 65(1): 29-36
Inal O, Kiliçarslan M, Ari N, Baykara T

Matrix formulations of Eudragit E 100: NE 40D polymers (100:0, 70:30, 60:40, 50:50% w/w) with 20% w/w of triacetine and 5% w/w of atenolol were prepared by film casting method with different solvents (methanol, 2-propanol and acetone). In vitro release of atenolol from the films were studied by vertical Franz diffusion cells in HEPES buffer (pH 7.4) for 78 h. Direct currents of 0.1 and 0.5 mA/cm2 were applied for 6 h to the formulations with Ag/AgCl electrodes. Also, transdermal application for the Eudragit E 100: NE 40 D (70:30% w/w) formulation was compared by iontophoresis or oleic acid (2.5% w/v) with control group on Wistar rats. As a result, the in vitro release rate of atenolol from films were increased with iontophoresis by increasing the current density (from 0.240 to 0.424 mg/cm2 for 70:3% w/w formulation) and also increased with the amount of Eudragit NE 40D (from 0.646 to 1.30 mg/cm2 at the end of 78 h). It is obtained from the in vivo studies that oleic acid provided a higher plasma and skin concentration (0.825 mg/mL and 12.5 mg/cm2, respectively) than iontophoresis treatment (0.399 mg/mL and 1.81 mg/cm2, respectively) due to the different mechanisms. However, the results showed that iontophoresis is a good alternative for enhancing the transdermal delivery of atenolol.

Stepwise two-color laser photolysis studies of alpha-cleavage in highly excited triplet states of alpha-acyl-4-phenylphenols.

Photochem Photobiol Sci. 2008 Jun; 7(6): 711-7
Yamaji M

The photochemical properties of alpha-cleavage of C-O bond in highly excited triplet states (T(n) with n>2) of p-biphenyl acetate and p-biphenyl benzoate (Me-OBP and Ph-OBP) in solution were investigated in comparison with those in the lowest excited singlet and triplet states by using single laser and sequential two-color two-laser photolysis techniques. Upon 266 nm laser photolysis of Me-OBP and Ph-OBP, occurrence of C-O bond cleavage in the excited singlet state was recognized from the observation of the formation of p-phenylphenoxy radical (PPR) in the transient absorption. The quantum yields (Phi(rad)) of the PPR formation were determined to be 0.29 and 0.24 for Me-OBP and Ph-OBP, respectively. Triplet sensitization using acetone (Ac) provided efficient formation of the lowest triplet states (T(1)) of Me-OBP and Ph-OBP, and the molar absorption coefficients of the triplet-triplet absorption were determined. No photochemical reactions were found in the T(1) state. Upon 355 nm laser flash photolysis of the T(1) states of Me-OBP and Ph-OBP, formation of PPR accompanied with decomposition of the triplet state was confirmed in the transient absorption. This observation indicated that alpha-cleavage proceeds in the highly excited triplet state. The quantum yields (Phi(dec)) of the decomposition in the dissociative highly excited triplet state (T(R)) were determined to be 0.25 and 0.15 for Me-OBP and Ph-OBP, respectively. The reaction mechanism for alpha-bond cleavage in the T(R) state was discussed.

Intact Adelta-fibers up-regulate transient receptor potential A1 and contribute to cold hypersensitivity in neuropathic rats.

Neuroscience. 2008 Jun 26; 154(3): 1054-66
Ji G, Zhou S, Carlton SM

Mechanisms underlying cold hypersensitivity in neuropathic states are unclear. Recent data indicate both transient receptor potential (TRP) M8 and TRPA1 play a role. In relation to TRPA1, there are reported increases in mRNA. However, it is unknown whether TRPA1 mRNA is translated into functional receptors, whether these receptors are found on peripheral nociceptors and what population of primary afferents expresses the receptors. The present study provides several lines of evidence that TRPA1 receptors are expressed on intact primary sensory neurons and contribute to cold hypersensitivity following spinal nerve ligation (SNL). Immunohistochemical studies show that expression of TRPA1 is significantly increased in the ipsilateral compared with the contralateral L4 dorsal root ganglion (DRG). Using mustard oil (MO, selective TRPA1 agonist), Ca(2+) imaging demonstrates an increase in the percentage of MO-sensitive L4 DRG cells in SNL compared with sham and naive rats. The magnitude of the Ca(2+) response evoked by MO is also significantly larger in SNL compared with sham and naive rats. Behavioral studies demonstrate that SNL results in increased nocifensive behaviors to mechanical and cold stimulation that is not seen in sham or naive rats. Behavioral responses in sham rats are no different from naive rats. In vitro single fiber recordings demonstrate Adelta-fibers (intact L4 axons) in the nerve-injured hind paw have conduction velocities no different from naive rats. In contrast, compared with naive rats, mechanical thresholds of the Adelta-fibers in SNL rats are significantly decreased, the proportion of cold-sensitive and MO-sensitive Adelta-fibers is significantly increased and the response magnitude of Adelta-fibers to MO is significantly increased. MO-induced activity in Adelta-fibers is significantly reduced by Ruthenium Red (TRPA1 receptor antagonist). These results demonstrate that TRPA1 is expressed on peripheral nociceptors, and they are up-regulated on intact Adelta-fibers following nerve injury, contributing to cold hypersensitivity.

Transcriptional regulation of ketone body-utilizing enzyme, acetoacetyl-CoA synthetase, by C/EBPalpha during adipocyte differentiation.

Biochim Biophys Acta. 2008 Jun-Jul; 1779(6-7): 414-9
Hasegawa S, Yamasaki M, Inage T, Takahashi N, Fukui T

Acetoacetyl-CoA synthetase (AACS), an essential enzyme for the Synthesis of fatty acid and cholesterol from ketone bodies, was found to be highly expressed in mouse adipose tissue, and GC box and C/EBPs motif were crucial for AACS promoter activity in 3T3-L1 adipocytes. Moreover, we found that AACS promoter activity was controlled mainly by C/EBPalpha during adipogenesis.

Metabolic effects of the very-low-carbohydrate diets: misunderstood "villains" of human metabolism.

J Int Soc Sports Nutr. 2004; 1(2): 7-11
Manninen AH

ABSTRACT : During very low carbohydrate intake, the regulated and controlled production of ketone bodies causes a harmless physiological state known as dietary ketosis. ketone bodies flow from the liver to extra-hepatic tissues (e.g., brain) for use as a fuel; this spares glucose metabolism via a mechanism similar to the sparing of glucose by oxidation of fatty acids as an alternative fuel. In comparison with glucose, the ketone bodies are actually a very good respiratory fuel. Indeed, there is no clear requirement for dietary carbohydrates for human adults. Interestingly, the effects of ketone body metabolism suggest that mild ketosis may offer therapeutic potential in a variety of different common and rare disease states. Also, the recent landmark study showed that a very-low-carbohydrate diet resulted in a significant reduction in fat mass and a concomitant increase in lean body mass in normal-weight men. Contrary to popular belief, insulin is not needed for glucose uptake and utilization in man. Finally, both muscle fat and carbohydrate burn in an amino acid flame.

Caspase-related apoptosis in chronic ischaemic microangiopathy following experimental vein occlusion in mini-pigs.

Acta Ophthalmol. 2008 May; 86(3): 302-6
Donati G, Kapetanios A, Dubois-Dauphin M, Pournaras CJ

PURPOSE: Acute brain ischaemia (stroke) causes a central area of coagulation necrosis. Peripheral to it and after a few hours, apoptosis causes neurons throughout the entire area to die progressively. However, this sequence of events is related to the reperfusion of regenerated capillaries or collateral circulation, and is considered to be potentially salvageable. Similar findings have been reported in the retina after ischaemia-reperfusion injury in rats. In the present study, we intended to investigate whether delayed cell death is involved in neuronal injuries to the inner retina during chronic retinal ischaemia. METHODS: Experimental branch retinal vein occlusion (BRVO) was induced in miniature pigs using indirect argon laser. The eyes were prelevated at 4, 24 and 48 hours and at 1 and 3 weeks following BRVO. The caspase inhibitor Z-VAD was injected intravitreally 24 hours after BRVO. Affected retinas were examined 24 hours later for any protective effect from apoptotic cell death. Histological examination with cresyl violet staining and TUNEL (TdT-mediated dUTP-biotin nick-end labelling) was performed on the samples. RESULTS: A progressive oedema of the nerve fibre, ganglion cell and inner plexiform layers, related to a widely diffused cell necrosis, was observed in the affected territory within 4-24 hours after BRVO. This was followed by a wave of apoptosis localized at the periphery of the affected territory, which peaked approximately 48 hours after BRVO and was associated with a diffuse oedema of the inner nuclear layer. A progressive atrophy of the inner retina was observed 1-3 weeks after BRVO. Injection of the caspase inhibitor Z-VAD (24 hours after BRVO) decreased the amount of apoptotic cell bodies 48 hours after BRVO. CONCLUSIONS: This study shows that although necrosis is the predominant form of neuronal death in the early phase, massive delayed neuronal cell death caused by apoptosis occurs on a widespread basis as a result of chronic ischaemia after BRVO in the retina. Further studies are needed to evaluate the possibility of rescuing retinal neurons from death by neuroprotective treatments.

Surface modification of natural fibers using bacteria: depositing bacterial cellulose onto natural fibers to create hierarchical fiber reinforced nanocomposites.

Biomacromolecules. 2008 Jun; 9(6): 1643-51
Pommet M, Juntaro J, Heng JY, Mantalaris A, Lee AF, Wilson K, Kalinka G, Shaffer MS, Bismarck A

Triggered biodegradable composites made entirely from renewable resources are urgently sought after to improve material recyclability or be able to divert materials from waste streams. Many biobased polymers and natural fibers usually display poor interfacial adhesion when combined in a composite material. Here we propose a way to modify the surfaces of natural fibers by utilizing bacteria ( Acetobacter xylinum) to deposit nanosized bacterial cellulose around natural fibers, which enhances their adhesion to renewable polymers. This paper describes the process of modifying large quantities of natural fibers with bacterial cellulose through their use as substrates for bacteria during fermentation. The modified fibers were characterized by scanning electron microscopy, single fiber tensile tests, X-ray photoelectron spectroscopy, and inverse gas chromatography to determine their surface and mechanical properties. The practical adhesion between the modified fibers and the renewable polymers cellulose acetate butyrate and poly(L-lactic acid) was quantified using the single fiber pullout test.

[Extracellular glycosyl hydrolase activity of the clostridia producing acetone, butanol, and ethanol]

Prikl Biokhim Mikrobiol. 2008 Jan-Feb; 44(1): 49-55
Berezina OV, Sineokiĭ SP, Velikodvorskaia GA, Schwarz W, Zverlov VV

Production of acetone, butanol, ethanol, acetic acid, and butyric acid by three strains of anaerobic bacteria, which we identified as Clostridium acetobutylicum, was studied. The yield of acetone and alcohols in 6% flour medium amounted to 12.7-15 g/l with butanol constituting 51.0-55.6%. Activities of these strains towards xylan, beta-glucan, carboxymethylcellulose, and crystalline and amorphous celluloses were studied. C. acertobutylicum 6, C. acetoburylicum 7, and C. acertobutylicum VKPM B-4786 produced larger amounts of acetone and alcohols and displayed higher cellulase and hemicellulase activities than the type strain C. acetobutylicum ATCC 824. It was demonstrated that starch in the medium could be partially substituted with plant biomass.