Catabolism - an overview | ScienceDirect Topics (2023)

Biology of Acute Catabolism: Mineral and Antioxidant Alterations

Along with changes in macronutrients, inflammatory responses cause alterations in micronutrients (vitamins and minerals) from baseline physiology (Table 5.8).^9,19 The most prominent of these responses is anemia, as IL-1 and TNF cause reduction in blood iron and zinc content.^9,15,30 Since many microorganisms use iron and zinc as growth factors, it is speculated that these acute decreases in serum concentrations are part of protective immune responses against invading microorganisms.^9,15,30 Moreover, these elements are decreased in serum, but they are not excreted from the body; they are stored in the liver and can be used again in cellular metabolism for the host after infection has resolved.^9,15,30 While serum concentrations of both zinc and iron decrease, plasma copper concentrations rise because of the significant increase in ceruloplasmin, an additional acute phase protein.^9,15,30 Deficiencies of water-soluble vitamins may also be identified, as diuresis begins during the resolution of the acute phase of stress.^9,15,30

Amino Acids

Catabolism of amino acids for energy production is increased by protein intake in excess of requirements, or starvation, stress, and illness. The multiple specific steps in pathways of amino acid catabolism are complex, but commonly generate reduced NAD or FAD (NADH or FADH) that provide a source of electrons, entering the electron transport chain and oxidative phosphorylation. Disorders of amino acid catabolism commonly result in ‘organic acidurias,’ which sometimes interfere with mitochondrial oxidation of other energy substrates. The clinical and metabolic consequences of these disorders most commonly have CNS manifestations.

Catabolism of Testosterone

The primary site of catabolism of circulating testosterone and 5α-DHT is the liver.¹³⁰ Testosterone and 5α-DHT are taken up in the liver, and testosterone is converted to an inactive metabolite, 5β-DHT, by the enzyme 5β-reductase. Both 5α- and 5β-DHT then undergo 3α-reduction by the 3α-HSD enzymes to form 3α,5α-androstanediol (also called3α-diol) and 3α,5β-androstanediol, respectively; this is followed by 17β-oxidation by the enzyme 17β-HSD type 2 to form androsterone and etiocholanolone ascatabolic products. In peripheral tissues such as skin, 5α-DHT may also be converted to 3α-diol, which is further metabolized in the liver.

In the liver, testosterone, DHT, androsterone, etiocholanolone, and the 3α-androstanediols undergo glucuronidation and, to a lesser degree, sulfation, to form more hydrophilic conjugates that are released into the circulation and excreted in urine and bile. Metabolic inactivation of testosterone primarily involves its conversion to metabolites such as androstenedione (about 50%), androsterone (20%), and etiocholanolone (20%) glucuronides (as well as sulfates) and lesser conversion to 3α-diol glucuronides (3α-diol Gs). Because 3α-diol comes mostly from skin, blood and urine measurements of 3α-diol G have been used as a marker of peripheral androgen action.¹³⁰ In men with 5α-reductase deficiency, 3α-diol G concentrations are reduced. The amount of body hair and acne correlates with 3α-diol G concentrations.

Epitestosterone (17α-hydroxy-4-androsten-3-one) is a biologically inactive 17α-hydroxy epimer of testosterone (17β-hydroxy-4-androsten-3-one) that is produced by the testes in response to LH.¹³¹ The production rate of epitestosterone is about 3% that of testosterone, but its clearance rate is 33% that of testosterone, and there is no interconversion of epitestosterone and testosterone. Like testosterone, epitestosterone is conjugated in the liver, primarily to glucuronides and sulfates, and excreted in the urine. Because epitestosterone conjugates are rapidly cleared in the urine, excretion rates of testosterone and epitestosterone are similar, and the ratio of urinary testosterone to epitestosterone (T/E ratio) is approximately 1:1.

Measurements of the T/E ratio and other metabolites in urine by sensitive gas chromatography/mass spectrometry methods are used to detect androgenic anabolic steroid doping, particularly testosterone, by competitive athletes.¹³¹ Administration of exogenous testosterone suppresses LH and the production and clearance of epitestosterone relative to the administered testosterone, resulting in an elevated T/E ratio in urine. The World and United States Anti-Doping Agencies have set a threshold T/E ratio of greater than 4:1 as suspicious for testosterone doping.

Catabolism of BCAAs

Catabolic Losses

Both the metabolic shift to a catabolic predominance and the acidosis move potassium and phosphate from the cell to the serum. The osmotic diuresis, the kaliuretic effect of the hyperaldosteronism, and the ketonuria then accelerate renal losses of potassium and phosphate. Sodium is also lost with the diuresis, but free water losses are greater than isotonic losses. With prolonged illness and severe DKA, total body losses can approach 10-13 mEq/kg of sodium, 5-6 mEq/kg of potassium, and 4-5 mEq/kg of phosphate. These losses continue for several hours during therapy until the catabolic state is reversed and the diuresis is controlled. For example, 50% of infused sodium may be lost in the urine during IV therapy. Even though the sodium deficit may be repaired within 24 hr intracellular potassium and phosphate may not be completely restored for several days.

Although patients with DKA have a total body potassium deficit, the initial serum level is often normal or elevated. This is caused by the movement of potassium from the intracellular space to the serum, both as part of the ketoacid buffering process and as part of the catabolic shift. These effects are reversed with therapy, and potassium returns to the cell. Improved hydration increases renal blood flow, allowing for increased excretion of potassium in the elevated aldosterone state. The net effect is often a dramatic decline in serum potassium levels, especially in severe DKA. This can precipitate changes in cardiac conductivity, flattening of T waves, and prolongation of the QRS complex and can cause skeletal muscle weakness or ileus. The risk of myocardial dysfunction is increased with shock and acidosis. Potassium levels must be closely followed and electrocardiographic monitoring continued until DKA is substantially resolved. Potassium should be added to the IV fluids once serum potassium declines below 5.5 mEq/L and titrated as outlined inTable 607.6. A 1 : 1 mixture of potassium chloride (or acetate) and potassium phosphate is typically used. Rarely, the IV insulin must be temporarily held if serum potassium levels drop below 3 mEq/L. It is unclear whether phosphate deficits contribute to symptoms of DKA such as generalized muscle weakness. In pediatric patients, a deficit has not been shown to compromise oxygen delivery via a deficiency of 2,3-diphosphoglycerate. In most cases, the inclusion of potassium phosphate as outlined above will be sufficient; however additional IV supplementation with potassium phosphate can be used if needed.

Pancreatitis (usually mild) is occasionally seen with DKA, especially if prolonged abdominal distress is present; serum amylase and lipase may be elevated. If the serum lipase is not elevated, the amylase is likely nonspecific or salivary in origin. Serum creatinine adjusted for age may be falsely elevated owing to interference by ketones in the autoanalyzer methodology. An initial elevated value rarely indicates renal failure and should be rechecked when the child is less ketonemic. Blood urea nitrogen may be elevated with prerenal azotemia and should be rechecked as the child is rehydrated. Mildly elevated creatinine or blood urea nitrogen is not a reason to withhold potassium therapy if good urinary output is present.

Some indirect indexes using lymphocytes and other factors

The anabolism index evaluates the absolute rate of anabolism as a result of corticotropic, gonadotropic, and thyrotropic considerations of relative and absolute activity. (cf. catabolism-anabolism index under “Indirect indexes using neutrophils” and the catabolism index under “Indirect indexes using LDH or CPK” for a further discussion). A low rate of catabolism in and of itself does not mean that the rate of anabolism is low. Each level of activity can be elevated, low, or normal. The anabolism index seeks to evaluate the quantitative rate of anabolisms. The catabolism index as a quantitative assessment of catabolism is in the numerator. The lower the absolute rate of catabolism, the greater the predominance of anabolism may be. However, the relative rate of catabolism to anabolism rate the greater the predominance of anabolism.

As noted above, the higher the lymphocyte levels, the less well adapted the thyroid is in its catabolic activity, thus the lower the rate of catabolism will be. The greater the genital ratio corrected, the greater the predominance of androgens relative to estrogens in adaptation, which favors the completion of anabolism.

Apoptosis was first described in 1847. For 140years (1847–1987), the study of apoptosis was morphologic in nature. From 1988, with the discovery of bcl-2 protein, the genetic mechanisms of apoptosis have been the primary focus of study.³⁶⁷ From the Endobiogenic perspective, because the endocrine system manages the rate of metabolism of the cell, it mediates the life of the cell and the time of apoptosis or necrosis or lack thereof, such as with cancer cells.

The plethora of pro- and antiapoptotic signaling factors are the means of regulating apoptosis and while interesting, are not the determinant of when and to what degree of intensity apoptosis occurs (or does not). The validity of such an index would allow for a global approach to managing apoptosis that is concordant with the general scheme of factors related to cancer growth, and away from the endless search for “silver bullets” in pharmacotherapy—natural or synthetic—that are highly target with respect to specific mechanisms of apoptosis, but carry the risk of potentially more serious side effects.

The numerator is composed of the Anabolism index and the Nucleomembrane index. The greater the numerator, the greater the rate of apoptosis is. Cell growth occurs as a result of anabolism, which requires increased activity at the level of the nucleus with respect protein transcription (represented by the Nucleomembrane index) relative to membrane activity. The greater the anabolic activity of the cell, the sooner it will reach the end of its programmed number of division, and hence die by apoptosis.

The denominator is composed of the membrane expansion index, which is itself composed of the product of the catabolism and the growth index corrected indices. When there is catabolic predominance,^{368, 369} and/or elevated IGF activity^{370, 371} the membrane expands.³⁷² A greater rate of membrane expansion relative to that of structural activity implies that more energy is devoted to cellular hyperplasia than to cellular divisions, hence the longer it takes for the cell to die due to reaching its programmed time of death.

In summary, the endocrine system is the regulator of apoptosis, while pro-apoptotic proteins are the mechanism of apoptotic cell death. From the Endobiogenic perspective, an endocrine approach to the evaluation of the global physiologic rate of apoptosis allows one to evaluate the reason for apoptosis (or its insufficiency) and to pinpoint the causative factors, and thus allows for a clinical plan to address these particular imbalances. In contrast, merely enumerating the number of pro- or anti-apoptosis factors active does not at this time offer a path of clinical intervention.

7.18.11 Conclusion

Cofactor catabolism is still an understudied area in cofactor chemistry and much research needs to be done to identify catabolic intermediates, the enzymes that catalyze the formation of these intermediates and the corresponding genes that encode these enzymes. A better knowledge of the in vivo stability of the cofactors is important for understanding cellular homeostasis and has potential applications in the biotechnology of vitamin production by fermentation as well as determining the sensitivity of the cell to antibiotics targeted toward vitamin biosynthetic enzymes. Cofactor catabolism is also likely to reveal new and interesting enzymology, as already found, for example, in heme and PLP catabolism (e.g., heme oxygenase and MHPCO).

27.11 Catabolism of Pyrimidine Nucleotides

Pyrimidine catabolism occurs mainly in the liver. In contrast to purine catabolism, pyrimidine catabolism yields highly soluble end products. Pyrimidine nucleotides are converted to nucleosides by 5'-nucleotidase.

Cytidine so formed is converted to uridine by cytidine aminohydrolase, while uridine and thymidine are converted to free bases by pyrimidine nucleoside phosphorylase.

High concentrations of BAIB in urine follow excessive cell turnover or destruction (e.g., owing to leukemias or radiation therapy). High levels of BAIB excretion has been observed in some Asian families. Its significance is not known and the high excretors are otherwise normal. Degradation of β-alanine and BAIB or their reutilization in various biosynthetic pathways is possible.

2.1 Overview of catabolism

Stage 1 takes a very large number of simple units and partially oxidizes them to give three major compounds, acetyl coenzyme A, α-oxoglutarate and oxaloacetate, and three minor ones, pyruvate, fumarate and succinyl coenzyme A. Many of the reaction sequences have sections in common – for example all the hexoses are fed into the earlier steps of glycolysis. Because this stage involves only partial oxidations, the energy released is only about one-third of the total possible.

Stage 2 is the complete oxidation of the six compounds from stage 1 to give carbon dioxide. This is the major route in the cell for energy trapping and the remaining two-thirds of the energy is released. It is conserved as NADH, fpH₂ and a little as ATP directly.

Stage 3 involves the reoxidation of the reduced coenzymes so that their hydrogens are released as water. The energy is finally transferred to ATP by the phosphorylation of ADP.

Amino Acids Can Be Used to Generate ATP

Amino acids can be used to build body proteins and they can be broken down to yield energy. In the steady state of the adult, the body store of proteins remains constant and there is a constant throughput of amino acids, equal to the dietary intake, that is converted to metabolic energy. In the typical American diet, about 16% of the calories are provided by dietary protein.

Because the hepatic portal blood leaves the intestines and travels to the liver, the liver has the first opportunity to metabolize all the nutrients, including the amino acids absorbed from digested proteins in the intestinal lumen. The liver does several things: it catabolizes a large fraction of the amino acids (57%), releases some unchanged into the general circulation (23%), and utilizes some 20% for synthesis of proteins that either remain in the liver or are released into the blood.