Protein Catabolism and Protein Synthesis in Perfused Livers of Normal and Alloxan-Diabetic Rats

Green, Morris; Miller, Leon L.

doi:10.1016/s0021-9258(20)81337-4

Cited by 105 publications

(7 citation statements)

References 14 publications

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“…The profiles of adenine nucleotide concentrations in control livers (Table 2, rows [25][26][27][28][29][30][31][32] show the expected values of the [ATP]/[AMP] ratio (12,88), energy charge (7), and mass action ratio of the myokinase reaction (31). In the presence of 3HP, the pool of adenine nucleotides was doubled, and the (87).…”

Section: Resultsmentioning

confidence: 96%

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Inter-relations between 3-hydroxypropionate and propionate metabolism in rat liver: relevance to disorders of propionyl-CoA metabolism

Wilson

Han

Zhang

et al. 2017

American Journal of Physiology-Endocrinology and Metabolism

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Propionate, 3-hydroxypropionate (3HP), methylcitrate, related compounds, and ammonium accumulate in body fluids of patients with disorders of propionyl-CoA metabolism, such as propionic acidemia. Although liver transplantation alleviates hyperammonemia, high concentrations of propionate, 3HP, and methylcitrate persist in body fluids. We hypothesized that conserved metabolic perturbations occurring in transplanted patients result from the simultaneous presence of propionate and 3HP in body fluids. We investigated the inter-relations of propionate and 3HP metabolism in perfused livers from normal rats using metabolomic and stable isotopic technologies. In the presence of propionate, 3HP, or both, we observed the following metabolic perturbations. First, the citric acid cycle (CAC) is overloaded but does not provide sufficient reducing equivalents to the respiratory chain to maintain the homeostasis of adenine nucleotides. Second, there is major CoA trapping in the propionyl-CoA pathway and a tripling of liver total CoA within 1 h. Third, liver proteolysis is stimulated. Fourth, propionate inhibits the conversion of 3HP to acetyl-CoA and its oxidation in the CAC. Fifth, some propionate and some 3HP are converted to nephrotoxic maleate by different processes. Our data have implications for the clinical management of propionic acidemia. They also emphasize the perturbations of the liver intermediary metabolism induced by supraphysiological, i.e., millimolar, concentrations of labeled propionate used to trace the intermediary metabolism, in particular, inhibition of CAC flux and major decreases in the [ATP]/[ADP] and [ATP]/[AMP] ratios.

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Section: Resultsmentioning

confidence: 96%

“…Proteolysis and ureagenesis. Isolated livers perfused without nitrogenous substrates release amino acids and urea (32). This reflects tissue proteolysis, amino acid catabolism, and ureagenesis.…”

Section: Resultsmentioning

confidence: 99%

Inter-relations between 3-hydroxypropionate and propionate metabolism in rat liver: relevance to disorders of propionyl-CoA metabolism

Wilson

Han

Zhang

et al. 2017

American Journal of Physiology-Endocrinology and Metabolism

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“…Such an interpretation is in line with the autoradiographic findings, which indicate that labeled proteins first appear in the rough ER and later are concentrated in the smooth ER, Golgi cisternae, and Golgi vacuoles . Taken as a group, the plasma proteins make up the bulk of proteins synthesized by the liver (5,42,43) . From experiments on the distribution of TCA-precipitated label, it can be calculated that the microsomal fraction, within 30 min after administration, Figs .…”

Section: Discussionmentioning

confidence: 99%

Evidence for the Participation of the Golgi Apparatus in the Intracellular Transport of Nascent Albumin in the Liver Cell

Glaumann

Ericsson

1970

The Journal of Cell Biology

117

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A comparative biochemical and radioautographic in vivo study was performed to identify the site of synthesis and route of migration of albumin in the parenchymal liver cell after labeling with leucine-' 4 C or leucine-3 H via the portal vein. Free cytoplasmic ribosomes, membrane-bound ribosomes, rough-and smooth-surfaced microsomes, and Golgi membranes were isolated . The purity of the Golgi fraction was examined morphologically and biochemically. After administration of leucine-' 4C, labeled albumin was extracted, and the sequence of transport was followed from one fraction to the other . Approximately 2 min after the intravenous injection, bound ribosomes displayed a maximal rate of leucine-14C incorporation into albumin . 4 min later, a peak was reached for rough microsomes.Corresponding maximal activities for smooth microsomes were recorded at 15 min, and for the Golgi apparatus at -20 min . The relative amount of albumin, calculated on a membrane protein basis, was higher in the Golgi fraction than in the microsomes . By radioautography the silver grains were preferentially localized over the rough-surfaced endoplasmic reticulum at the 5 min interval . Apparent activity in the Golgi zone was noted 9 min after the injection ; at 15 and 20 min, the majority of the grains were found in this location. Many of the grains associated with the Golgi apparatus were located over Golgi vacuoles containing 300-800 A electron-opaque bodies . It is concluded that albumin is synthesized on bound ribosomes, subsequently is transferred to the cavities of rough-surfaced endoplasmic reticulum, and then undergoes migration to the smooth-surfaced endoplasmic reticulum and the Golgi apparatus . In the latter organelle, albumin can be expected to be segregated together with very low density lipoprotein in vacuoles known to move toward the sinusoidal portion of the cell and release their content to the blood .

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“…The liver is one of the organs which retains a high level of protein synthesis in the adult animal (35) . It produces proteins for secretion and for replacement of its own substance in about equal amounts (18,51) . The use of conventional cell fractionation techniques has established that most liver proteins are formed on ribosomes (30,31), and that at least some of the proteins produced for secretion to the plasma move from a region of granular membranes (isolated as rough-surfaced microsomes) through a region of agranular membranes (isolated as smooth-surfaced microsomes) and thence to the circulation (28,41) .…”

Section: Introductionmentioning

confidence: 99%

“…The need to avoid bifunctional fixatives such as glutaraldehyde in studies of this type has been demonstrated previously (44) . Free leucine taken up by liver is not catabolized into other low molecular weight compounds to a significant extent (15,18), probably due to the lack of the necessary transaminases (10), and is utilized primarily for protein synthesis (15) . Hence, bound tritium atoms can be equated with newly formed protein, rather than with other substances such as lipids into which catabolites of leucine might have been incorporated .…”

Section: Introductionmentioning

confidence: 99%

Electron Microscopic Radioautographic Detection of Sites of Protein Synthesis and Migration in Liver

Ashley

Peters

1969

The Journal of Cell Biology

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The sites of synthesis of proteins and their subsequent migration in rat liver have been studied during a 75 min period after labeling of liver-slice proteins by exposure to leucine-H3 for 2 min. Incorporation of the label into protein began after 1 min and was maximal by 4 min. Electron microscopic radioautography showed that synthesis of proteins in hepatocytes occurs mainly on ribosomes, particularly those in rough endoplasmic reticulum and, to some extent, in nuclei and mitochondria. Most of the newly formed proteins leave the endoplasmic reticulum in the course of 40 min, and concurrently labeled proteins appear in Golgi bodies, smooth membranes, microbodies, and lysosomes. A likely pathway for the secretion of some or all plasma proteins is from typical rough endoplasmic reticulum to a zone of reticulum which is partially coated with ribosomes, to the Golgi apparatus, and thence to the cell periphery. The formation of protein by reticuloendothelial cells was measured and found to be about 5% of the total protein formed by the liver.

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Protein Catabolism and Protein Synthesis in Perfused Livers of Normal and Alloxan-Diabetic Rats

Cited by 105 publications

References 14 publications

Inter-relations between 3-hydroxypropionate and propionate metabolism in rat liver: relevance to disorders of propionyl-CoA metabolism

Inter-relations between 3-hydroxypropionate and propionate metabolism in rat liver: relevance to disorders of propionyl-CoA metabolism

Evidence for the Participation of the Golgi Apparatus in the Intracellular Transport of Nascent Albumin in the Liver Cell

Electron Microscopic Radioautographic Detection of Sites of Protein Synthesis and Migration in Liver

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