Control of ribosome synthesis in bacteria: the important role of rRNA chain elongation rate

We present here a study on the role of leptin in the regulation of lipogenesis by examining the effect of dietary macronutrient composition on lipogenesis in the leptin receptor-defective Zucker diabetic fatty rat (ZDF) and its lean litter mate (ZL). Animals were pair fed two isocaloric diets differing in their fat-to-carbohydrate ratio providing 10 and 30% energy as fat. Lipogenesis was measured in the rats using deuterated water and isotopomer analysis. From the deuterium incorporation into plasma palmitate, stearate, and oleate, we determined de novo synthesis of palmitate and synthesis of stearate by chain elongation and of oleate by desaturation. Because the macronutrient composition and the caloric density were controlled, changes in de novo lipogenesis under these dietary conditions represent adaptation to changes in the fat-to-carbohydrate ratio of the diet. De novo lipogenesis was normally suppressed in response to the high-fat diet in the ZL rat to maintain a relatively constant amount of lipids transported. The ZDF rat had a higher rate of lipogenesis, which was not suppressed by the high-fat diet. The results suggest an important hormonal role of leptin in the feedback regulation of lipogenesis.

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Key role of l-alanine in the control of hepatic protein synthesis

Biochemical Journal ◽

10.1042/bj2410491 ◽

1987 ◽

Vol 241 (2) ◽

pp. 491-498 ◽

Cited By ~ 26

Author(s):

D Pérez-Sala ◽

R Parrilla ◽

M S Ayuso

Keyword(s):

Amino Acids ◽

Protein Synthesis ◽

Physiological Role ◽

Chain Elongation ◽

Liver Protein ◽

Isolated Liver Cells ◽

Metabolic Transformation ◽

Hepatic Protein Synthesis

We investigated the effects of administration of single amino acids to starved rats on the regulation of protein synthesis in the liver. Of all the amino acids tested, only alanine, ornithine and proline promoted statistically significant increases in the extent of hepatic polyribosome aggregation. The most effective of these was alanine, whose effect of promoting polyribosomal aggregation was accompanied by a decrease in the polypeptide-chain elongation time. The following observations indicate that alanine plays an important physiological role in the regulation of hepatic protein synthesis. Alanine was the amino acid showing the largest decrease in hepatic content in the transition from high (fed) to low (starved) rates of protein synthesis. The administration of glucose or pyruvate is also effective in increasing liver protein synthesis in starved rats, and their effects were accompanied by an increased hepatic alanine content. An increase in hepatic ornithine content does not lead to an increased protein synthesis, unless it is accompanied by an increase of alanine. The effect of alanine is observed either in vivo, in rats pretreated with cycloserine to prevent its transamination, or in isolated liver cells under conditions in which its metabolic transformation is fully impeded.

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Chain Elongation of Aromatic Amino Acids: the Role of 2-Benzylmalic Acid in the Biosynthesis of a C6C4 Amino Acid and a C6C3 Mustard Oil Glucoside

Canadian Journal of Biochemistry ◽

10.1139/o74-129 ◽

1974 ◽

Vol 52 (10) ◽

pp. 916-921 ◽

Cited By ~ 8

Author(s):

D. Dörnemann ◽

W. Löffelhardt ◽

H. Kindl

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Aromatic Amino Acids ◽

Chain Elongation ◽

Mustard Oil ◽

Barbarea Vulgaris ◽

Nasturtium Officinale ◽

A Chain ◽

Phenylbutyric Acid

A chemical synthesis of specifically 14C-labelled 2-benzylmalic acid, hitherto unknown, was developed. 4-Phenylacetoacetate obtained by condensation of phenylacetyl chloride-1-14C with ethyl acetoacetate yielded 2-benzylmalic acid-2-14C after cyanohydrin reaction and hydrolysis.2-Benzylmalic acid-2-14C, administered to shoots of Nasturtium officinale and Barbarea vulgaris, was shown to be an efficient precursor of the aglucone moiety of the mustard oil glucoside gluconasturtiin. The incorporation of radioactivity agreed well with the values reported for incorporation of 3-benzylmalic acid, but was considerably higher than that obtained after application of L-phenylalanine-U-14C. A conversion of 2-benzylmalic acid into 3-benzylmalic acid and 2-amino-4-phenylbutyric acid could also be demonstrated. These findings provide the final evidence for a chain-lengthening mechanism leading to homologous amino acids as proposed by Underbill and Wetter in 1966.

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The role of chain elongation systems in the supplying of fatty acids to the adipocyte membrane lipids

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism ◽

10.1016/0005-2760(77)90003-0 ◽

1977 ◽

Vol 487 (2) ◽

pp. 269-276 ◽

Cited By ~ 14

Author(s):

J.-P. Giacobino ◽

M. Chmelar

Keyword(s):

Fatty Acids ◽

Membrane Lipids ◽

Chain Elongation

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Roles of EXTL2, a member of the EXT family of tumour suppressors, in liver injury and regeneration processes

Biochemical Journal ◽

10.1042/bj20130323 ◽

2013 ◽

Vol 454 (1) ◽

pp. 133-145 ◽

Cited By ~ 13

Author(s):

Satomi Nadanaka ◽

Shoji Kagiyama ◽

Hiroshi Kitagawa

Keyword(s):

Liver Injury ◽

Knockout Mice ◽

Weight Ratio ◽

Hepatocyte Proliferation ◽

Chain Elongation ◽

Wild Type ◽

Ccl4 Administration ◽

Ccl4 Treatment ◽

Regeneration Processes

The gene products of two members of the EXT (exostosin) gene family, EXT1 and EXT2, function together as a polymerase in the biosynthesis of heparan sulfate. EXTL2 (EXT-like 2), one of the three EXTL genes in the human genome that are homologous to EXT1 and EXT2, encodes an N-acetylhexosaminyltransferase. We have demonstrated that EXTL2 terminates chain elongation of GAGs (glycosaminoglycans), and thereby regulates GAG biosynthesis. The abnormal GAG biosynthesis caused by loss of EXTL2 had no effect on normal development or normal adult homoeostasis. Therefore we examined the role of EXTL2 in CCl4 (carbon tetrachloride)-induced liver failure, a model of liver disease. On the fifth day after CCl4 administration, the liver/body weight ratio was significantly smaller for EXTL2-knockout mice than for wild-type mice. Consistent with this observation, hepatocyte proliferation following CCl4 treatment was lower in EXTL2-knockout mice than in wild-type mice. EXTL2-knockout mice experienced less HGF (hepatocyte growth factor)-mediated signalling than wild-type mice specifically because GAG synthesis was altered in these mutant mice. In addition, GAG synthesis in hepatic stellate cells was up-regulated during liver repair in EXTL2-knockout mice. Taken together, the results of the present study indicated that EXTL2-mediated regulation of GAG synthesis was important to the tissue regeneration processes that follow liver injury.

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The role of ribosomal ribonucleic acid in the structure and function of mammalian brain ribosomes

Biochemical Journal ◽

10.1042/bj1430419 ◽

1974 ◽

Vol 143 (2) ◽

pp. 419-426 ◽

Cited By ~ 3

Author(s):

Barbara Kay Grove ◽

Terry C. Johnson

Keyword(s):

Protein Synthesis ◽

Protein Interactions ◽

Chemical Properties ◽

Chain Elongation ◽

Synthetic Activity ◽

Mammalian Brain ◽

28S Rrna ◽

Diethylaminoethyl Cellulose ◽

Brain Ribosomes

In order to resolve the functional role of intact rRNA in polypeptide chain elongation mouse brain ribosomes were treated with dilute pancreatic or T1 RNAase (ribonuclease). After RNAase treatment, several physical–chemical properties as well as the functional activity of the ribosomes were measured. RNAase treatment resulted in the extensive hydrolysis of both 18S and 28S rRNA; however, the sedimentation properties of mono-ribosomes were unaltered and more than 90% of the relatively low-molecular-weight RNA fragments remained associated with ribosome particles. Analysis of the ability of RNAase-treated ribosomes to participate in cell-free protein synthesis showed that ribosomes with less than 2% intact rRNA retained more than 85% of their activity in polyphenylalanine incorporation. Proof that the incorporation of phenylalanine by ribosomes with hydrolysed rRNA actually represented active translocation was obtained by the effective inhibition of incorporation by diphtheria toxin. In addition, the oligopeptide products of protein synthesis could be identified by BD (benzoylated diethylaminoethyl)-cellulose column chromatography. Analysis of the size distribution of oligopeptides synthesized by normal and RNAase-treated ribosomes showed no significant differences which indicated that there was no change in the proportion of ribosomes engaged in protein synthesis. Thus strong RNA–protein and protein–protein interactions must serve to maintain the functional integrity of ribosomes even when the rRNA is extensively degraded. The ability of the enzyme-treated ribosomes to efficiently incorporate amino acids clearly demonstrated that ‘intact’ rRNA is not required for protein-synthetic activity.

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