Fractional catabolic rate

According to Krempler et al. (K36) the fractional catabolic rate of Lp(a) of homozygous FH patients is only marginally less than that of normal individuals. 

IgGi and IgG, seem to cross the placenta readily whereas IgG, and IgGi cross in lower concentrations (W2). These IgG subclasses which cross the placenta readily may have a faster catabolic rate than the other IgG subclasses. IgG, has a fractional catabolic rate (FCR) of 17% and Ti/-, of 8 days whereas T,/, for total IgG is 22 days with an FCR of 7% (S14). This physicochemical property of IgG subclasses is no doubt related to the lower IgG values found in African cord blood than in their respective maternal blood. 

However, the reductase inhibitors clearly induce an increase in high-affinity LDL receptors. This effect increases both the fractional catabolic rate of LDL and the liver s extraction of LDL precursors (VLDL remnants), thus reducing plasma LDL (Figure 35-2). Because of marked first-pass hepatic extraction, the major effect is on liver. Preferential activity in liver of some congeners appears to be attributable to tissue-specific differences in uptake. Limited reduction of LDL levels in patients who lack functional LDL receptors indicates that decreases in de novo cholesterologenesis also contribute to cholesterol reduction. Modest decreases in plasma triglycerides and small increases in HDL also occur. 

Decreased catabolism of chylomicrons and VLDL has been demonstrated in nephrotic syndrome (D4). The fractional catabolic rate of apoliprotein B depends on the presence of hypertriglyceridemia The fractional catabolic rate of... 

Other drugs that have an impact on serum lipids have also been examined. Probucol pretreatment has been shown to lower the rate of restenosis after balloon angioplasty in clinical trials (88,89). Although its lipid-lowering effect is due to an increase in the fractional catabolic rate of LDL cholesterol (90), its antirestenotic effect is believed to be related to other properties, including inhibition of LDL oxidation, promotion of endothelial regeneration, and anti-inflammatory effects (91). However, probucol is not widely available due to its ability to lower HDL-cholesterol and concerns relating to proarrhythmia. 

The kinetics of LDL catabolism in normal subjects have been examined in a number of studies. Miller has recently summarized data from 29 studies (M33). When considered together, these studies on 94 men and 22 women give a mean fractional catabolic rate for LDL in men of0.352 0.098 per day ( SD) and in women 0.339 0.101 per day. 

Newborn babies have a low plasma LDL cholesterol, between 25 and 50 mg/100 ml (K36), a level similar to that found in many animal species (C2, M35). Goldstein and Brown have hypothesized that the marked rise which occurs in industrialized man, with LDL-cholesterol levels of over 100 mg/100 ml, may be attributed to suppression of LDL receptors as a result of environmental factors (B55, G19). They adduce evidence from studies on LDL turnover performed by Bilheimer and others that indicates that dogs, baboons, and humans each produce about 15 mg LDL cholesterol per kilogram body weight per day, but the very marked differences in plasma LDL-cholesterol levels in these species is the result of a fractional catabolic rate lower in the baboon than in the dog and much lower in man (G19). Miller also summarizes evidence from others suggesting that the slow rise in plasma LDL concentration seen with age in men and women is associated with a corresponding fall in the fractional catabolic rate of LDL, and he hypothesizes that the decrease in efficiency of LDL clearance with advancing age is a consequence of a decrease in either the number or the function of LDL (B-100,E) receptors (M33). 

Krempler et al. measured the turnover of apo(a) in nine individuals with serum apo(a) levels ranging from 1 to 68 mg/100 ml. The fractional catabolic rate was similar in all, and elevated apo(a) levels seemed to be the consequence of increased apo(a) synthesis (K30). Lp(a), containing apo(a) and apoB, binds to the same receptor site on cultured fibroblasts as LDL, before being internalized and degraded (H12). It may be that Lp(a) is an atherogenic lipoprotein because it contains apoB, and is subject to similar degra-dative processes as LDL. 

A 6-year-old girl was admitted to a metabolic study unit with extensive skin xanthomas, serum cholesterol of 1100 mg/dL, and triglyceride of 369 mg/dL. Radio-actively tagged LDL showed a fractional catabolic rate of 0.12 pools/day (normal is 0.43 pools/day). The girl suffered a heart attack soon thereafter, after which a coronary artery bypass operation was performed. Another was performed 6 weeks thereafter and finally, the patient received a heart and liver transplant. Her cholesterol then fell down to 270 mg/dL and the fractional catabolic rate of administered LDL had increased to 0.31 pools/day. Address the following ... 

Understand the factors that control cellular protein degradation and turnover be able to solve problems involving protein half-lives and fractional catabolic rates and understand how whole-body protein turnover may be estimated. 

It was just stated that protein turnover has anabolic and catabolic arms. In a subject in a steady metabolic state, these are exactly equal. It may then be of interest to determine the absolute rates of protein synthesis/degradation. Individual protein turnover rates may be expressed in terms of half-lives (tiy) or fractional catabolic rates or simply in terms of grams protein synthesized and degraded per unit time. The same parameters can be derived for whole-body protein turnover. 

Which equation is not able to give you the correct fractional catabolic rate, assuming that all other necessary data are available See text for abbreviations. 

An alternative approach to determining requirements is to measure the fractional rate of catabolism of the vitamin by use of a radioactive tracer, then determine the intake that would be required to maintain an appropriate level of liver reserves. As discussed in Section2.2.1.1, when the liver concentration rises above 70 /rmol per kg, there is increased activity of the microsomal oxidation of vitamin A and biliary excretion of retinol metabolites. The fractional catabolic rate is 0.5% per day assuming 50% efficiency of storage of dietary retinol, this gives a mean requirement of 6.7 /rg per kg of body weight and a reference intake of 650 to 700 /rg for adult men (Olson, 1987a). Reference intakes for vitamin A are shown in Table 2.4. 

Elimination rate constant kg (units 1/time). This is the fraction of drug that is irreversibly cleared from the accessible pool per unit time. (In some literature, this is referred to as the fractional clearance or fractional catabolic rate.)... 

The quantitative relationship between cholesterol intake and cholesterol levels is still controversial, especially because in humans, there appears to be a high individual variability in processing of dietary cholesterol. However, numerous animal and human studies support the concept that dietary cholesterol can raise LDL-cholesterol levels and change the size and composition of these particles as well. LDL particles become larger in size and enriched in cholesterol esters. Mechanisms contributing to these events include an increase in hepatic synthesis of apoB-containing lipoproteins, increased conversion of VLDL remnants to LDL, or a decrease in the fractional catabolic rate for LDL. Reduced LDL receptor activity due to an increase in hepatic cholesterol content, secondary to excess dietary cholesterol, may lead to a decreased uptake of both LDL and VLDL remnants. 

Global kinetics, however, allowed calculation of some parameters in normal volunteers, i.e., fractional catabolic rate, rate of synthesis, and mean residence time determined by the mathematical analysis of both plasma decay curves and urinary excretion rates. Such studies demonstrated different metaboUsms for Apo C-I, C-II, and C-III. They may supply essential information on the perturbations observed in pathology. 

Bilheimer et al. described a very impressive experiment demonstrating the role of the liver in LDL degradation [10]. A combined liver-heart transplantation was performed as treatment for the homozygous form of familial hypercholesterolemia. After transplantation of the hver from a normal donor, the patient s extremely high plasma LDL-cholesterol level was normalized and her fractional catabolic rate of LDL increased several-fold. 

The experimental data of plasma and urine radioactivities were analyzed by the non-compartmental approach (Rescigno and Gurpide, 1973), as described in details previously (Bianchi et al., 1979). The formulas utilized in this approach allow to determine the following parameters of uric acid kinetics total metabolic clearance rate (MCR), mean residence time of the tracer, total distribution volume (TDV, plasma equivalent), fractional catabolic rate (FCR, relative to TDV), and clearance rate of C-uric acid via the renal route (MCR] ). The total turnover rate (TR) and the total pool of exchangeable uric acid are then obtained as the product of, respectively MCR or TDV by the plasma urate concentration. The extrarenal disposal of uric acid (bacterial uricolysis in the gut, skin desquamation) is determined as the difference between the total metabolic clearance rate and the clearance rate of uric acid through the kidney route. 

Niacin decreases the fractional catabolic rate of apo Al metabolism without altering its synthetic rate (Blum et al. 1977 Shepherd et al. 1979). Furthermore, niacin was selective in its uptake of HDL apo Al but not HDL cholesterol... 

C is rapidly excreted. About 4% of this pool is lost daily (fractional catabolic rate) after intermission of vitamin C supply. The biological half-time of the pool is therefore approximately 8-40 days (Homig, 1981). The first symptoms of scurvy occur upon reaching a total body pool of 300-400 mg. Table II shows data on the turnover rate of ascorbic acid for man and different species. Table III shows the ascorbic acid concentrations in organs and body fluids of the adult man. 

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