The Catabolism of AcetylCoA

The Catabolism Release Co2

Mayes, PhD, DSc, & David A. Bender, PhD The citric acid cycle (Krebs cycle, tricarboxylic acid cycle) is a series of reactions in mitochondria that oxidize acetyl residues (as acetyl-CoA) and reduce coenzymes that upon reoxidation are linked to the formation of ATP. The citric acid cycle is the final common pathway for the aerobic oxidation of carbohydrate, lipid, and protein because glucose, fatty acids, and most amino acids are metabolized to acetyl-CoA or intermediates of the...

Cardiac Muscle Resembles Skeletal Muscle In Many Respects

The general picture of muscle contraction in the heart resembles that of skeletal muscle. Cardiac muscle, like skeletal muscle, is striated and uses the actin-myosin-tropomyosin-troponin system described above. Unlike skeletal muscle, cardiac muscle exhibits intrinsic rhyth-micity, and individual myocytes communicate with each other because of its syncytial nature. The T tubular system is more developed in cardiac muscle, whereas the sarcoplasmic reticulum is less extensive and consequently the...

Biomedical Importance

An adult human weighing 70 kg requires about 10-12 MJ (2400-2900 kcal) from metabolic fuels each day. This requirement is met from carbohydrates (40-60 ), lipids (mainly triacylglycerol, 30-40 ), protein (1015 ), and alcohol if consumed. The mix being oxidized varies depending on whether the subject is in the fed or starving state and on the intensity of physical work. The requirement for metabolic fuels is relatively constant throughout the day, since average physical activity only increases...

Catecholamines Thyroid Hormones Are Made From Tyrosine

Catecholamines Are Synthesized in Final Form & Stored in Secretion Granules Three amines dopamine, norepinephrine, and epinephrine are synthesized from tyrosine in the chromaffin cells of the adrenal medulla. The major product of the adrenal medulla is epinephrine. This compound constitutes about 80 of the catecholamines in the medulla, and it is not made in extramedullary tissue. In contrast, most of the norepinephrine present in organs innervated by sympathetic nerves is made in situ...

Some Hormones Have Plasma Transport Proteins

The class I hormones are hydrophobic in chemical nature and thus are not very soluble in plasma. These hormones, principally the steroids and thyroid hormones, have specialized plasma transport proteins that serve several purposes. First, these proteins circumvent the solubility problem and thereby deliver the hormone to the target cell. They also provide a circulating reservoir of the hormone that can be substantial, as in the case of the thyroid hormones. Hormones, when bound to the transport...

Many Hormones Are Made From Cholesterol

The adrenal steroid hormones are synthesized from cholesterol. Cholesterol is mostly derived from the plasma, but a small portion is synthesized in situ from acetyl-CoA via mevalonate and squalene. Much of the cholesterol in the adrenal is esterified and stored in cy-toplasmic lipid droplets. Upon stimulation of the adrenal by ACTH, an esterase is activated, and the free cholesterol formed is transported into the mitochondrion, where a cytochrome P450 side chain cleavage enzyme (P450scc)...

Mutations Affecting Membrane Proteins Cause Diseases

In view of the fact that membranes are located in so many organelles and are involved in so many processes, it is not surprising that mutations affecting their protein constituents should result in many diseases or disorders. Proteins in membranes can be classified as receptors, transporters, ion channels, enzymes, and structural components. Members of all of these classes are often glycosylated, so that mutations affecting this process may alter their function. Examples of diseases or...

Purines Pyrimidines Nucleosides Nucleotides

Purines and pyrimidines are nitrogen-containing hete-rocycles, cyclic compounds whose rings contain both carbon and other elements (hetero atoms). Note that the smaller pyrimidine has the longer name and the larger purine the shorter name and that their six-atom rings are numbered in opposite directions (Figure 33-1). The planar character of purines and pyrimidines facilitates their close association, or stacking, which stabilizes double-stranded DNA (Chapter 36). The oxo and amino groups of...

The Major Components Of Cartilage Are Type Ii Collagen Certain Proteoglycans

The principal proteins of hyaline cartilage (the major type of cartilage) are listed in Table 48-11. Type II collagen is the principal protein (Figure 48-13), and a number of other minor types of collagen are also present. In Figure 48-13. Schematic representation of the molecular organization in cartilage matrix. Link proteins noncovalently bind the core protein (lighter color) of proteoglycans to the linear hyaluronic acid molecules (darker color). The chondroitin sulfate side chains of the...

Adipose Tissue Is The Main Store Of Triacylglycerol In The Body

The triacylglycerol stores in adipose tissue are continually undergoing lipolysis (hydrolysis) and reesterifica-tion (Figure 25-7). These two processes are entirely different pathways involving different reactants and enzymes. This allows the processes of esterification or lipolysis to be regulated separately by many nutritional, metabolic, and hormonal factors. The resultant of these two processes determines the magnitude of the free fatty acid pool in adipose tissue, which in turn determines...

Many Metabolic Genetic Disorders Involve Bone

A number of the more important examples of metabolic and genetic disorders that affect bone are listed in Table 48-10. Osteogenesis imperfecta (brittle bones) is characterized by abnormal fragility of bones. The scleras are often abnormally thin and translucent and may appear blue owing to a deficiency of connective tissue. Four types of this condition (mild, extensive, severe, and variable) have been recognized, of which the extensive type occurring in the newborn is the most ominous. Affected...

Proteoglycans Have Numerous Functions

As indicated above, proteoglycans are remarkably complex molecules and are found in every tissue of the body, mainly in the ECM or ground substance. There they are associated with each other and also with the other major structural components of the matrix, collagen and elastin, in quite specific manners. Some proteoglycans bind to collagen and others to elastin. These interactions are important in determining the structural organization of the matrix. Some proteogly-cans (eg, decorin) can also...

Clinical Aspects

In prolonged starvation, as adipose tissue reserves are depleted there is a very considerable increase in the net rate of protein catabolism to provide amino acids not only as substrates for gluconeogenesis but also as the main metabolic fuel of the tissues. Death results when essential tissue proteins are catabolized beyond the point at which they can sustain this metabolic drain. In patients with cachexia as a result of release of cytokines in response to tumors and a number of other...

Inhibitors of Folate Metabolism Provide Cancer Chemotherapy Antibacterial Antimalarial Drugs

The methylation of deoxyuridine monophosphate (dUMP) to thymidine monophosphate (TMP), catalyzed by thymidylate synthase, is essential for the synthesis of DNA. The one-carbon fragment of methy-lene-tetrahydrofolate is reduced to a methyl group with release of dihydrofolate, which is then reduced back to tetrahydrofolate by dihydrofolate reductase. Thymi-dylate synthase and dihydrofolate reductase are especially active in tissues with a high rate of cell division. Methotrexate, an analog of...

Vitamin D Is Really A Hormone

Vitamin D is not strictly a vitamin since it can be synthesized in the skin, and under most conditions that is its major source. Only when sunlight is inadequate is a dietary source required. The main function of vitamin D is in the regulation of calcium absorption and homeostasis most of its actions are mediated by way of nuclear receptors that regulate gene expression. Deficiency leading to rickets in children and osteomalacia in adults continues to be a problem in northern latitudes, where...

Water Is An Excellent Nucleophile

Metabolic reactions often involve the attack by lone pairs of electrons on electron-rich molecules termed nucleophiles on electron-poor atoms called elec-trophiles. Nucleophiles and electrophiles do not necessarily possess a formal negative or positive charge. Water, whose two lone pairs of sp electrons bear a partial negative charge, is an excellent nucleophile. Other nucleophiles of biologic importance include the oxygen atoms of phosphates, alcohols, and carboxylic acids the sulfur of thiols...

The Regulation of eIF4E Controls the Rate of Initiation

The 4F complex is particularly important in controlling the rate of protein translation. As described above, 4F is a complex consisting of 4E, which binds to the m7G cap structure at the 5' end of the mRNA, and 4G, which serves as a scaffolding protein. In addition to binding 4E, 4G binds to eIF-3, which links the complex to the 40S ribosomal subunit. It also binds 4A and 4B, the ATPase-helicase complex that helps unwind the RNA (Figure 38-7). 4E is responsible for recognition of the mRNA cap...

Dietary Vitamin E Deficiency in Humans Is Unknown

In experimental animals, vitamin E deficiency results in resorption of fetuses and testicular atrophy. Dietary deficiency of vitamin E in humans is unknown, though patients with severe fat malabsorption, cystic fibrosis, and some forms of chronic liver disease suffer deficiency because they are unable to absorb the vitamin or transport it, exhibiting nerve and muscle membrane damage. Premature infants are born with inadequate reserves of the vitamin. Their erythrocyte membranes are abnormally...

Biochemical Research Has Impact on Nutrition Preventive Medicine

One major prerequisite for the maintenance of health is that there be optimal dietary intake of a number of chemicals the chief of these are vitamins, certain amino acids, certain fatty acids, various minerals, and water. Because much of the subject matter of both biochemistry and nutrition is concerned with the study of various aspects of these chemicals, there is a close relationship between these two sciences. Moreover, more emphasis is being placed on systematic attempts to maintain health...

Synthetic Nucleotide Analogs Are Used In Chemotherapy

Synthetic analogs of purines, pyrimidines, nucleosides, and nucleotides altered in either the heterocyclic ring or the sugar moiety have numerous applications in clinical medicine. Their toxic effects reflect either inhibition of enzymes essential for nucleic acid synthesis or their incorporation into nucleic acids with resulting disruption of base-pairing. Oncologists employ 5-fluoro- or 5-iodouracil, 3-deoxyuridine, 6-thioguanine and 6-mer-captopurine, 5- or 6-azauridine, 5- or 6-azacytidine,...

Synthesis Of Polyunsaturated Fatty Acids Involves Desaturase Elongase Enzyme Systems

Additional double bonds introduced into existing mo-nounsaturated fatty acids are always separated from each other by a methylene group (methylene interrupted) except in bacteria. Since animals have a A9 desaturase, they are able to synthesize the 0)9 (oleic acid) family of unsaturated fatty acids completely by a combination of chain elongation and desaturation (Figure 23-3). However, as indicated above, linoleic (06) or a-linolenic (o3) acids required for the synthesis of the other members of...

Short Longterm Mechanisms Regulate Lipogenesis

Adenylate Kinase Phosphorylase

Long-chain fatty acid synthesis is controlled in the short term by allosteric and covalent modification of enzymes and in the long term by changes in gene expression governing rates of synthesis of enzymes. Acetyl-CoA Carboxylase Is the Most Important Enzyme in the Regulation of Lipogenesis Acetyl-CoA carboxylase is an allosteric enzyme and is activated by citrate, which increases in concentration in the well-fed state and is an indicator of a plentiful supply of acetyl-CoA. Citrate converts...

Ingestion Of Large Quantities Of Fructose Has Profound Metabolic Consequences

Diets high in sucrose or in high-fructose syrups used in manufactured foods and beverages lead to large amounts of fructose (and glucose) entering the hepatic portal vein. Fructose undergoes more rapid glycolysis in the liver than does glucose because it bypasses the regulatory step catalyzed by phosphofructokinase (Figure 20-5). This allows fructose to flood the pathways in the liver, leading to enhanced fatty acid synthesis, increased esterification of fatty acids, and increased VLDL...

Many Metabolic Fuels Are Interconvertible

Summary Metabolism Figure

Carbohydrate in excess of immediate requirements as fuel or for synthesis of glycogen in muscle and liver may be used for lipogenesis (Chapter 21) and hence triacyl-glycerol synthesis in both adipose tissue and liver (whence it is exported in very low density lipoprotein). The importance of lipogenesis in human beings is unclear in Western countries, dietary fat provides 35-45 of energy intake, while in less developed countries where carbohydrate may provide 60-75 of energy intake the total...

Free Fatty Acids Are Rapidly Metabolized

Generalized Lipoprotein Structure

The free fatty acids (FFA, nonesterified fatty acids, un-esterified fatty acids) arise in the plasma from lipolysis of triacylglycerol in adipose tissue or as a result of the action of lipoprotein lipase during uptake of plasma tri-acylglycerols into tissues. They are found in combination with albumin, a very effective solubilizer, in concentrations varying between 0.1 and 2.0 eq mL of plasma. Levels are low in the fully fed condition and rise to 0.7-0.8 eq mL in the starved state. In...

The Reactions Of Glycolysis Constitute The Main Pathway Of Glucose Utilization

Lipoic Acid Pathway Include Tdp

The overall equation for glycolysis from glucose to lac-tate is as follows Glucose + 2ADP + 2Pi 2l(+) - Lactate + 2ATP + 2H2O All of the enzymes of glycolysis (Figure 17-2) are found in the cytosol. Glucose enters glycolysis by phos-phorylation to glucose 6-phosphate, catalyzed by hexokinase, using ATP as the phosphate donor. Under physiologic conditions, the phosphorylation of glucose to glucose 6-phosphate can be regarded as irreversible. Hexokinase is inhibited allosterically by its product,...

Hormones Regulate Fat Mobilization

Fat Mobilization

Insulin Reduces the Output of Free Fatty Acids The rate of release of free fatty acids from adipose tissue is affected by many hormones that influence either the rate of esterification or the rate of lipolysis. Insulin inhibits the release of free fatty acids from adipose tissue, which is followed by a fall in circulating plasma free fatty acids. It enhances lipogenesis and the synthesis of acylglycerol and increases the oxidation of glucose to CO2 via the pentose phosphate pathway. All of...

The Porphyrias Are Genetic Disorders Of Heme Metabolism

The porphyrias are a group of disorders due to abnormalities in the pathway of biosynthesis of heme they can be genetic or acquired. They are not prevalent, but it is important to consider them in certain circumstances eg, in the differential diagnosis of abdominal pain and of a variety of neuropsychiatric findings otherwise, patients will be subjected to inappropriate treatments. It has been speculated that King George III had a type of porphyria, which may account for his periodic...

Biosynthesis of Fatty Acids

Malonyl Coa Palmitate

Mayes, PhD, DSc, amp Kathleen M. Botham, PhD, DSc Fatty acids are synthesized by an extramitochondrial system, which is responsible for the complete synthesis of palmitate from acetyl-CoA in the cytosol. In the rat, the pathway is well represented in adipose tissue and liver, whereas in humans adipose tissue may not be an important site, and liver has only low activity. In birds, lipogenesis is confined to the liver, where it is particularly important in providing lipids for egg...

Blood Glucose Is Derived From The Diet Gluconeogenesis Glycogenolysis

Liver Glut Transporter Bidirectional

The digestible dietary carbohydrates yield glucose, galactose, and fructose that are transported via the hepatic portal vein to the liver where galactose and fructose are readily converted to glucose Chapter 20 . Metabolic amp Hormonal Mechanisms Regulate the Concentration of the Blood Glucose The maintenance of stable levels of glucose in the blood is one of the most finely regulated of all homeostatic mechanisms, involving the liver, extrahepatic tissues, and several hormones. Liver cells are...

Polysaccharides Serve Storage Structural Functions

Polysaccharides include the following physiologically important carbohydrates. Starch is a homopolymer of glucose forming an a-glucosidic chain, called a glucosan or glucan. It is the most abundant dietary carbohydrate in cereals, pota toes, legumes, and other vegetables. The two main constituents are amylose 15-20 , which has a non-branching helical structure Figure 13-12 and amy-lopectin 80-85 , which consists of branched chains composed of 24-30 glucose residues united by 1 4 linkages in the...

Six Amino Acids Form Pyruvate

All of the carbons of glycine, serine, alanine, and cys-teine and two carbons of threonine form pyruvate and subsequently acetyl-CoA. Glycine. The glycine synthase complex of liver mitochondria splits glycine to CO2 and NH4 and forms N5,N 10-methylene tetrahydrofolate Figure 30-5 . Glycinuria results from a defect in renal tubular reabsorption. The defect in primary hyperoxaluria is the failure to catabolize glyoxylate formed by deamination of glycine. Subsequent oxidation of glyoxylate to...

Glycogenolysis Is Not The Reverse Of Glycogenesis But Is A Separate Pathway Figure 181

Glycogen phosphorylase catalyzes the rate-limiting step in glycogenolysis by promoting the phosphorylytic cleavage by inorganic phosphate phosphorylysis cf hy- Glycogen 1 4 and 6 glucosyl units x Uridine disphosphate glucose UDPGlc Free glucose from debranching enzyme Free glucose from debranching enzyme To glycolysis and pentose phosphate pathway Figure 18-1. Pathway of glycogenesis and of glycogenolysis in the liver. Two high-energy phosphates are used in the incorporation of 1 mol of glucose...

Biomedically Glucose Is The Most Important Monosaccharide

Alpha Glycerose

The Structure of Glucose Can Be Represented in Three Ways The straight-chain structural formula aldohexose Figure 13 1A can account for some of the properties of glucose, but a cyclic structure is favored on thermo-dynamic grounds and accounts for the remainder of its chemical properties. For most purposes, the structural formula is represented as a simple ring in perspective as proposed by Haworth Figure 13-1B . In this representation, the molecule is viewed from the side and above the plane...

Gluconeogenesis Control of the Blood Glucose

Glycogen Entering Glycolysis

Mayes, PhD, DSc, amp David A. Bender, PhD Gluconeogenesis is the term used to include all pathways responsible for converting noncarbohydrate precursors to glucose or glycogen. The major substrates are the glucogenic amino acids and lactate, glycerol, and propionate. Liver and kidney are the major gluco-neogenic tissues. Gluconeogenesis meets the needs of the body for glucose when carbohydrate is not available in sufficient amounts from the diet or from glycogen reserves. A supply of...