The Concentration Of Blood Glucose Is Regulated Within Narrow Limits

In the postabsorptive state, the concentration of blood glucose in most mammals is maintained between 4.5 and 5.5 mmol L. After the ingestion of a carbohydrate meal, it may rise to 6.5-7.2 mmol L, and in starvation, it may fall to 3.3-3.9 mmol L. A sudden decrease in blood glucose will cause convulsions, as in insulin overdose, owing to the immediate dependence of the brain on a supply of glucose. However, much lower concentrations can be tolerated, provided progressive adaptation is allowed....

Cholesterol Synthesis Is Controlled By Regulation Of HmgcoA Reductase

Regulation of cholesterol synthesis is exerted near the beginning of the pathway, at the HMG-CoA reductase step. The reduced synthesis of cholesterol in starving animals is accompanied by a decrease in the activity of the enzyme. However, it is only hepatic synthesis that is inhibited by dietary cholesterol. HMG-CoA reductase in liver is inhibited by mevalonate, the immediate product of the pathway, and by cholesterol, the main product. Cholesterol (or a metabolite, eg, oxygenated sterol)...

Proteases May Be Secreted As Catalytically Inactive Proenzymes

Certain proteins are synthesized and secreted as inactive precursor proteins known as proproteins. The proproteins of enzymes are termed proenzymes or zymogens. Selective proteolysis converts a proprotein by one or more successive proteolytic clips to a form that exhibits the characteristic activity of the mature protein, eg, its enzymatic activity. Proteins synthesized as proproteins include the hormone insulin (proprotein proinsulin), the digestive enzymes pepsin, trypsin, and chymotrypsin...

Adenosine Deaminase Purine Nucleoside Phosphorylase Deficiency

Adenosine deaminase deficiency is associated with an immunodeficiency disease in which both thymus-derived lymphocytes (T cells) and bone marrow-derived lymphocytes (B cells) are sparse and dysfunctional. Purine nucleoside phosphorylase deficiency is associated with a severe deficiency of T cells but apparently normal B cell function. Immune dysfunctions appear to result from accumulation of dGTP and dATP, which inhibit ribonucleotide reductase and thereby deplete cells of DNA precursors....

References

Hudgins LC et al Human fatty acid synthesis is stimulated by a eucaloric low fat, high carbohydrate diet. J Clin Invest 1996 97 2081. Jump DB et al Coordinate regulation of glycolytic and lipogenic gene expression by polyunsaturated fatty acids. J Lipid Res 1994 35 1076. Kim KH Regulation of mammalian acetyl-coenzyme A carboxy-lase. Annu Rev Nutr 1997 17 77. Salati LM, Goodridge AG Fatty acid synthesis in eukaryotes. In Biochemistry of Lipids, Lipoproteins and Membranes. Vance DE, Vance JE...

Vitamin B6 Has Several Roles in Metabolism

Pyridoxal phosphate is a coenzyme for many enzymes involved in amino acid metabolism, especially in transamination and decarboxylation. It is also the co-factor of glycogen phosphorylase, where the phosphate group is catalytically important. In addition, vitamin B6 is important in steroid hormone action where it removes the hormone-receptor complex from DNA binding, terminating the action of the hormones. In vitamin Bg deficiency, this results in increased sensitivity to the actions of low...

Mismatch Repair

Mismatch repair corrects errors made when DNA is copied. For example, a C could be inserted opposite an A, or the polymerase could slip or stutter and insert two to five extra unpaired bases. Specific proteins scan the newly synthesized DNA, using adenine methylation within a GATC sequence as the point of reference (Figure 36-22). The template strand is methylated, and the newly synthesized strand is not. This difference allows the repair enzymes to identify the strand that contains the errant...

Clinical Aspects

Deficiency of Lung Surfactant Causes Respiratory Distress Syndrome Lung surfactant is composed mainly of lipid with some proteins and carbohydrate and prevents the alveoli from collapsing. Surfactant activity is largely attributed to dipalmitoylph osphatidylcholine, which is synthesized shortly before parturition in full-term infants. Deficiency of lung surfactant in the lungs of many preterm newborns gives rise to respiratory distress syndrome. Administration of either natural or artificial...

Biomedical Importance

Cholesterol is present in tissues and in plasma either as free cholesterol or as a storage form, combined with a long-chain fatty acid as cholesteryl ester. In plasma, both forms are transported in lipoproteins (Chapter 25). Cholesterol is an amphipathic lipid and as such is an essential structural component of membranes and of the outer layer of plasma lipoproteins. It is synthesized in many tissues from acetyl-CoA and is the precursor of all other steroids in the body such as corticosteroids,...

Occupies A Central Position In Nitrogen Metabolism

Transfer of amino nitrogen to a-ketoglutarate forms L-glutamate. Release of this nitrogen as ammonia is then catalyzed by hepatic L-glutamate dehydrogenase (GDH), which can use either NAD+ or NADP+ (Figure 29-5). Conversion of a-amino nitrogen to ammonia by the concerted action of glutamate aminotrans-ferase and GDH is often termed transdeamination. Liver GDH activity is allosterically inhibited by ATP, GTP, and NADH and activated by ADP. The reaction catalyzed by GDH is freely reversible and...

Eight Sugars Predominate In Human Glycoproteins

About 200 monosaccharides are found in nature however, only eight are commonly found in the oligosaccharide chains of glycoproteins (Table 47-4). Most of these sugars were described in Chapter 13. -Acetyl-neuraminic acid (NeuAc) is usually found at the termini of oligosaccharide chains, attached to subterminal galactose (Gal) or -acetylgalactosamine (GalNAc) residues. The other sugars listed are generally found in more internal positions. Sulfate is often found in glyco-proteins, usually...

Minerals Are Required For Both Physiologic Biochemical Functions

Many of the essential minerals (Table 45-2) are widely distributed in foods, and most people eating a normal mixed diet are likely to receive adequate intakes. The Table 45-2. Classification of essential minerals according to their function. Table 45-2. Classification of essential minerals according to their function. Involved in membrane function principal cations of extracellular-and intracellular fluids, respectively Function as prosthetic groups in enzymes Cobalt, copper, iron, molybdenum,...

Selectins Play Key Roles in Inflammation in Lymphocyte Homing

Leukocytes play important roles in many inflammatory and immunologic phenomena. The first steps in many of these phenomena are interactions between circulating leukocytes and endothelial cells prior to passage of the former out of the circulation. Work done to identify specific molecules on the surfaces of the cells involved in such interactions has revealed that leukocytes and endothelial cells contain on their surfaces specific lectins, called selectins, that participate in their...

Diversity Of The Endocrine System

Hormones Are Synthesized in a Variety of Cellular Arrangements Hormones are synthesized in discrete organs designed solely for this specific purpose, such as the thyroid (tri-iodothyronine), adrenal (glucocorticoids and mineralo-corticoids), and the pituitary (TSH, FSH, LH, growth hormone, prolactin, ACTH). Some organs are designed to perform two distinct but closely related functions. For example, the ovaries produce mature oocytes and the reproductive hormones estradiol and progesterone. The...

Nuclear Magnetic Resonance Spectroscopy

Nuclear magnetic resonance (NMR) spectroscopy, a powerful complement to x-ray crystallography, mea sures the absorbance of radio frequency electromagnetic energy by certain atomic nuclei. NMR-active isotopes of biologically relevant atoms include H, 13C, 15N, and 31P. The frequency, or chemical shift, at which a particular nucleus absorbs energy is a function of both the functional group within which it resides and the proximity of other NMR-active nuclei. Two-dimensional NMR spectroscopy...

Carbohydrates Occur In Cell Membranes In Lipoproteins

In addition to the lipid of cell membranes (see Chapters 14 and 41), approximately 5 is carbohydrate in glyco-proteins and glycolipids. Carbohydrates are also present in apo B of lipoproteins. Their presence on the outer surface of the plasma membrane (the glycocalyx) has been shown with the use of plant lectins, protein agglutinins that bind with specific glycosyl residues. For example, concanavalin A binds a-glucosyl and a-man-nosyl residues. Glycophorin is a major integral membrane...

Further Clinical Aspects

Glucosuria Occurs When the Renal Threshold for Glucose Is Exceeded When the blood glucose rises to relatively high levels, the kidney also exerts a regulatory effect. Glucose is continuously filtered by the glomeruli but is normally completely reabsorbed in the renal tubules by active transport. The capacity of the tubular system to reab-sorb glucose is limited to a rate of about 350 mg min, and in hyperglycemia (as occurs in poorly controlled diabetes mellitus) the glomerular filtrate may...

Specific Enzymes Act As Markers Of Compartments Separated By The Mitochondrial Membranes

Mitochondria have an outer membrane that is permeable to most metabolites, an inner membrane that is selectively permeable, and a matrix within (Figure 12-1). The outer membrane is characterized by the presence of various enzymes, including acyl-CoA synthetase and glycerolphosphate acyltransferase. Adenylyl kinase and creatine kinase are found in the intermembrane space. The phospholipid cardiolipin is concentrated in the inner membrane together with the enzymes of the respiratory chain.

Elastin Confers Extensibility Recoil On Lung Blood Vessels Ligaments

Elastin is a connective tissue protein that is responsible for properties of extensibility and elastic recoil in tissues. Although not as widespread as collagen, elastin is present in large amounts, particularly in tissues that require these physical properties, eg, lung, large arterial blood vessels, and some elastic ligaments. Smaller quantities of elastin are also found in skin, ear cartilage, and several other tissues. In contrast to collagen, there appears to be only one genetic type of...

Changes In The Conformation Of The Head Of Myosin Drive Muscle Contraction

How can hydrolysis of ATP produce macroscopic movement Muscle contraction essentially consists of the cyclic attachment and detachment of the S-1 head of myosin to the F-actin filaments. This process can also be referred to as the making and breaking of cross-bridges. The attachment of actin to myosin is followed by con-formational changes which are of particular importance in the S-1 head and are dependent upon which nu-cleotide is present (ADP or ATP). These changes result in the power...

Eukaryotic Promoters Are More Complex

It is clear that the signals in DNA which control transcription in eukaryotic cells are of several types. Two types of sequence elements are promoter-proximal. One of these defines where transcription is to commence along the DNA, and the other contributes to the mechanisms that control how frequently this event is to occur. For example, in the thymidine kinase gene of the herpes simplex virus, which utilizes transcription factors of its mammalian host for gene expression, there is a single...

Metabolic Pathways May Be Studied At Different Levels Of Organization

In addition to studies in the whole organism, the location and integration of metabolic pathways is revealed by studies at several levels of organization. At the tissue and organ level, the nature of the substrates entering and metabolites leaving tissues and organs is defined. At the subcellular level, each cell organelle (eg, the mitochondrion) or compartment (eg, the cytosol) has specific roles that form part of a subcellular pattern of metabolic pathways. At the Tissue and Organ Level, the...

Proteins Can Be Produced for Research Diagnosis

A practical goal of recombinant DNA research is the production of materials for biomedical applications. This technology has two distinct merits (1) It can supply large amounts of material that could not be obtained by conventional purification methods (eg, interferon, tissue plasminogen activating factor). (2) It can provide human material (eg, insulin, growth hormone). The advantages in both cases are obvious. Although the primary aim is to supply products generally proteins for treatment...

Rna Synthesis Is A Cyclical Process Involves Initiation Elongation Termination

The process of RNA synthesis in bacteria depicted in Figure 37-3 involves first the binding of the RNA holopolymerase molecule to the template at the promoter site to form a PIC. Binding is followed by a con-formational change of the RNAP, and the first nu-cleotide (almost always a purine) then associates with the initiation site on the P subunit of the enzyme. In the presence of the appropriate nucleotide, the RNAP catalyzes the formation of a phosphodiester bond, and the nascent chain is now...

The Citric Acid Cycle Plays A Pivotal Role In Metabolism

The citric acid cycle is not only a pathway for oxidation of two-carbon units it is also a major pathway for interconversion of metabolites arising from transamination and deamination of amino acids. It also provides the substrates for amino acid synthesis by transamination, as well as for gluconeogenesis and fatty acid synthesis. Because it functions in both oxidative and synthetic processes, it is amphibolic (Figure 16-4). The Citric Acid Cycle Takes Part in Gluconeogenesis, Transamination,...

R

CH2 CH2 O-(p (P) Mevalonate 3-phospho-5-diphosphate CH2 CH2 O-(p (P) Mevalonate 5-diphosphate CH3 CH CH2 CH O (p (P) Geranyl diphosphate CH3 CH CH2 CH O (p (P) Geranyl diphosphate Figure 26-2. Biosynthesis of squalene, ubiquinone, dolichol, and other polyisoprene derivatives. (HMG, 3-hydroxy-3-methylglutaryl x, cytokinin.) A farnesyl residue is present in heme a of cytochrome oxidase. The carbon marked with asterisk becomes C11 or C12 in squalene. Squalene synthetase is a microsomal enzyme all...

The Flux Of Metabolites In Metabolic Pathways Must Be Regulated In A Concerted Manner

Regulation of the overall flux through a pathway is important to ensure an appropriate supply, when required, of the products of that pathway. Regulation is achieved by control of one or more key reactions in the pathway, catalyzed by regulatory enzymes. The physicochemical factors that control the rate of an Figure 15-7. Intracellular location and overview of major metabolic pathways in a liver parenchymal cell. (AA metabolism of one or more essential amino acids AA metabolism of one or more...

Bacterial Promoters Are Relatively Simple

Bacterial promoters are approximately 40 nucleotides (40 bp or four turns of the DNA double helix) in length, a region small enough to be covered by an E coli RNA holopolymerase molecule. In this consensus promoter region are two short, conserved sequence elements. Approximately 35 bp upstream of the transcrip tion start site there is a consensus sequence of eight nu-cleotide pairs (5'-TGTTGACA-3') to which the RNAP binds to form the so-called closed complex. More proximal to the transcription...

Glycosylated Hemoglobin HbA1c

When blood glucose enters the erythrocytes it glycosylates the e-amino group of lysine residues and the amino terminals of hemoglobin. The fraction of hemoglobin glycosylated, normally about 5 , is proportionate to blood glucose concentration. Since the half-life of an erythrocyte is typically 60 days, the level of glycosylated hemoglobin (HbA1c) reflects the mean blood glucose concentration over the preceding 6-8 weeks. Measurement of HbA1c therefore provides valuable information for...

Elongation Also Is a Multistep Process Figure 388

Elongation is a cyclic process on the ribosome in which one amino acid at a time is added to the nascent peptide chain. The peptide sequence is determined by the order of the codons in the mRNA. Elongation involves several steps catalyzed by proteins called elongation factors (EFs). These steps are (1) binding of aminoacyl-tRNA to the A site, (2) peptide bond formation, and (3) translocation. A. Binding of Aminoacyl-tRNA to the A Site In the complete 80S ribosome formed during the process of...

Sanger Was The First To Determine The Sequence Of A Polypeptide

Mature insulin consists of the 21-residue A chain and the 30-residue B chain linked by disulfide bonds. Frederick Sanger reduced the disulfide bonds (Figure 4-3), Figure 4-3. Oxidative cleavage of adjacent polypeptide chains linked by disulfide bonds (shaded) by per-formic acid (left) or reductive cleavage by p-mercap-toethanol (right) forms two peptides that contain cysteic acid residues or cysteinyl residues, respectively. Figure 4-3. Oxidative cleavage of adjacent polypeptide chains linked...

Carbohydrates Are Aldehyde Or Ketone Derivatives Of Polyhydric Alcohols

(1) Monosaccharides are those carbohydrates that cannot be hydrolyzed into simpler carbohydrates They may be classified as trioses, tetroses, pentoses, hex-oses, or heptoses, depending upon the number of carbon atoms and as aldoses or ketoses depending upon whether they have an aldehyde or ketone group. Examples are listed in Table 13-1. (2) Disaccharides are condensation products of two monosaccharide units. Examples are maltose and sucrose. (3) Oligosaccharides are condensation products of...

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...

Catecholamines Thyroid Hormones Are Made From Tyrosine

Thyroglobulin Hydrolysis

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...

Collagen Type I Is Composed Of A Triple Helix Structure Forms Fibrils

All collagen types have a triple helical structure. In some collagens, the entire molecule is triple helical, whereas in others the triple helix may involve only a fraction of the structure. Mature collagen type I, containing approximately 1000 amino acids, belongs to the former type in it, each polypeptide subunit or alpha chain is twisted into a left-handed helix of three residues per turn (Figure 48-1). Three of these alpha chains are then wound into a right-handed superhelix, forming a...

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)...

Heme Is Synthesized From Succinylcoa Glycine

Heme is synthesized in living cells by a pathway that has been much studied. The two starting materials are suc-cinyl-CoA, derived from the citric acid cycle in mitochondria, and the amino acid glycine. Pyridoxal phosphate is also necessary in this reaction to activate glycine. The product of the condensation reaction between succinyl-CoA and glycine is a-amino-P-ketoadipic acid, which is rapidly decarboxylated to form a-amino-levulinate (ALA) (Figure 32-5). This reaction sequence is catalyzed...

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

Matrix Molecular Chondroitin Sulfate

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...

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

Application Server Databsse Server Cloud

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...

Analysis of Lactose Metabolism in E coli Led to the Operon Hypothesis

Jacob and Monod in 1961 described their operon model in a classic paper. Their hypothesis was to a large extent based on observations on the regulation of lactose metabolism by the intestinal bacterium E coli. The molecular mechanisms responsible for the regulation of the genes involved in the metabolism of lactose are now among the best-understood in any organism. P-Galactosidase hydrolyzes the P-galactoside lactose to galactose and glucose. The structural gene for P-galac-tosidase lacZ is...

Hyperbilirubinemia Causes Jaundice

When bilirubin in the blood exceeds 1 mg dL 17.1 lmol L , hyperbilirubinemia exists. Hyperbilirubine-mia may be due to the production of more bilirubin than the normal liver can excrete, or it may result from the failure of a damaged liver to excrete bilirubin produced in normal amounts. In the absence of hepatic damage, obstruction of the excretory ducts of the liver by preventing the excretion of bilirubin will also cause hyperbilirubinemia. In all these situations, bilirubin accumulates in...

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...

Metabolic Disorders Are Associated With Each Reaction Of The Urea Cycle

Metabolic disorders of urea biosynthesis, while extremely rare, illustrate four important principles 1 Defects in any of several enzymes of a metabolic pathway enzyme can result in similar clinical signs and symptoms. 2 The identification of intermediates and of ancillary products that accumulate prior to a metabolic block provides insight into the reaction that is impaired. 3 Precise diagnosis requires quantitative assay of the activity of the enzyme thought to be defective. 4 Rational therapy...

Urea Is The Major End Product Of Nitrogen Catabolism In Humans

Synthesis of 1 mol of urea requires 3 mol of ATP plus 1 mol each of ammonium ion and of the a-amino nitrogen of aspartate. Five enzymes catalyze the numbered Figure 29-8. The glutaminase reaction proceeds essentially irreversibly in the direction of glutamate and NH4 formation. Note that the amide nitrogen, not the a-amino nitrogen, is removed. reactions of Figure 29-9. Of the six participating amino acids, -acetylglutamate functions solely as an enzyme activator. The others serve as carriers...

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

Gluconeogenesis

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...