Adenosine Triphosphate ATP
ATP serves as the general free energy currency for virtually all cellular processes. Hydrolysis of ATP is used to drive countless biochemical reactions, including many that are not phosphorylations. It is a direct source of energy for cell motility, muscle contraction, and the specific transport of substances across membranes. The processes of photosynthesis and metabolism of nutrients are used mainly to produce ATP. It is probably no exaggeration to call ATP the single most important substance...
Figure 136 Energy and electron profile of anaerobic glycolysis
The main focus of Chapter 13 is the catabolism of glucose through glycolysis. Related, though lower -priority concepts include the catabolism of other sugars, polysaccharides, glycerol, and formation of lactate and ethanol. Key points to remember about glycolysis 1. Glycolysis can proceed by mechanisms that are either anaerobic (non-oxidative - little or no oxygen present) or aerobic (oxidative - oxygen present and electron transport and oxidative phosphorylation are occurring). 2. Glycolysis...
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UDP-galactose UDP-galactose UDP-glucose UDP-glucose- q-D-galactose-l-phosphate uridylyltransferase Uncoupling electron transport and oxidative phosphorylation Undecaprenol phosphate Unsaturated fatty acid oxidation Uracil Uric acid excess in purine degradation Uridine Uridine diphosphate Uridine monophosphate Uridine triphosphate Uridylyl transferase Uronic Acids Uroporphyrinogen I Uroporphyrinogen III Uses of biochemistry Utilization of ammonia UTP
Acyclovir Acycloguanosine
Hi Li Acyclovir is an antiviral drug used to treat herpesvirus infection. The basis of its action is that acyclovir resembles part of the guanosine nucleoside and is phosphorylated by the viral enzyme, deoxypyrimidine kinase. The phosphorylated triphosphate form of acyclovir is an inhibitor of the herpesvirus DNA polymerase. A related compound, ganciclovir, H2N works similarly. Uninfected cells do not efficiently phosphorylate acyclovir and ganciclovir, so DNA replication and virus growth are...
Inositol 145Triphosphate InsP
Hi L InsP3 is a second messenger in signal transduction made by cleaving phosphatidylinositol 4,5-bisphosphate with phospholipase C (see here). The two products of the reaction, sn-1,2-diacylglycerol and InsP3 both act as second messengers in signal transduction. See also Figure 23.14, Second Messenger Systems, G Proteins and Signal Transduction Figure 23.14 Signal transduction pathways involving phosphoinositide turnover. Figure 23.14 Signal transduction pathways involving phosphoinositide...
Generation of altered oxidized bases in DNA such as 8oxoguanine or 5hydroxyuracil and thymine
Glycol (see here also) is intensely mutagenic. The intracellular generation of reactive oxygen species causes the formation of DNA bases such as 8-oxoguanine (8-hydroxyguanine) or thymine glycol. 8-oxoguanine is the most significant product of oxidative DNA damage. One of the protective mechanisms is not a DNA repair enzyme, but a nucleotide hydrolase. In E. coli, 8-oxo-dGTP accumulates in oxygen-stressed cells, and an enzyme encoded by the mutT gene cleaves this altered nucleotide before it...
Antibody Resource Page
Antibodies are proteins manufactured by vertebrate immune systems that aid in defense against infectious agents and other substances foreign to the animal. It is estimated that a human is capable of synthesizing more than 10 million distinct antibodies. Most of this great diversity is generated through the action of precisely controlled gene rearrangements which occur during differentiation of many individual clones of cells, each clone specialized for the synthesis of one and only one...
Internet Links 1 Enkephalins
The Biology of Pleasure (endorphins and enkephalins) Figure 5.21 Structure of preproinsulin and its conversion to insulin. Li Figure 5.15 The primary structure of bovine insulin. G -He-VaJ-au GlivCys-C - Sat-Va Gys S L& wTyfGin fi& vTy Of Phe-Val Asn Gin His Leu-Cys-Gly-SBr-HiR Leu-Vai Glu AFa-Leu Tyr Leu-Val Cya Gly*Glu-Afgdy P'w-Plie Tyr Tir Pro-Lys-Ala Phe-Val Asn Gin His Leu-Cys-Gly-SBr-HiR Leu-Vai Glu AFa-Leu Tyr Leu-Val Cya Gly*Glu-Afgdy P'w-Plie Tyr Tir Pro-Lys-Ala In addition to...
See also Lipoproteins Coated Pits Receptor Mediated Endocytosis LDLs Clathrin
Familial Hypercholesterolemia (FH) is a hereditary disease. Individuals with FH typically have mutations affecting their LDL Receptor (see below). The result of these mutations is a higher than normal level of serum cholesterol. Individuals who are homozygous for the disease have very high levels of cholesterol in the blood and usually die of heart disease before age 20. People heterozygous for the disease have higher than normal cholesterol and are at high risk for heart attacks in their...
Hormonal Regulation of Fuel Metabolism
Actions of the Major Hormones (Table 23.2, Figure 23.2) Insulin (Figure 23.2) Glucagon (Figure 23.2, Figure 23.3) Epinephrine Responses to Metabolic Stress Starvation, Diabetes (Figure 23.4 Starvation (Diagram) Diabetes (Figure 23.5) Mechanisms of Hormone Action (Figure 23.6) An Outline of Hormone Action (Figure 12.13, Figure 13.18, Figure 21.34, Figure 23.7) Hierarchical Nature of Hormonal Control (Figure 23.8, Figure 23.9) Synthesis of Hormones Peptide Hormone Precursors (Figure 5.15, Figure...
Internet Link Lipid Transport
LDLs are lipoprotein complexes referred to as bad cholesterol because prolonged elevation of LDL levels leads to atherosclerosis. LDLs are the primary transport vehicle for cholesterol synthesized in the liver (See Figure 18.7). Oxidation of LDLs leads to foam cell formation and ultimately an atherosclerotic plaque. The primary apoprotein contained in LDLs is Apo B-100. LDLs transport cholesterol into target cells by binding to an LDL receptor and being absorbed into the cell by a process...
See also Biosynthesis of Glycoconjugates Figure 1616 Figure 1617
Covalent binding of carbohydrate to protein or lipid brings about large changes in the physical properties of these substances that allow them to serve specialized biochemical functions. Sulfated polysaccharides in glycoproteins, for example, are effective biological lubricants and linking carbohydrates to lipids allows them to be inserted into membranes. Mammalian glycoproteins are classified as O-linked or N-linked. N-linked glycoproteins contain an N-acetylglucosamine residue linked to the...
See also Fatty Acids Glycerol Diacylglycerol Diacylglycerol Lipase
Figure 23.4 shows how blood glucose levels are maintained in the body under varying dietary conditions. Blood glucose increases shortly after a carbohydrate-containing meal, which stimulates the secretion of insulin and suppresses the secretion of glucagon, in order to remove glucose from the blood. These effects promote the uptake of glucose into the liver, stimulate glycogen synthesis, and suppress glycogen breakdown. Activation of acetyl-CoA carboxylase in the liver stimulates fatty acid...
See also Kinase Cascade
Figure 18.34 Regulation of fatty acid synthesis in animal cells, such as liver cells. Figure 18.34 Regulation of fatty acid synthesis in animal cells, such as liver cells. Insulin is a peptide hormone that functions in lowering blood glucose levels. Insulin has several activities that accomplish this goal, summarized below 1. Insulin inhibits transcription of the enzyme phosphoenolpyruvate carboxykinase (PEPCK). PEPCK is a key enzyme in gluconeogenesis and transcription is the primary means of...
See also Receptor Mediated Endocytosis Lipoprotein Complexes in Fat Transport
Five major classes of lipoprotein complexes transport the hydrophobic fats through the aqueous environment of the bloodstream (Table 18.1 and Figure 18.7). Free lipids are all but undetectable in the blood. The protein components of the lipoprotein complexes (Table 18.2) are called apo(lipo)proteins. A summary of the functions of the various lipoprotein complexes is as follows Chylomicrons - Chylomicrons emulsify dietary lipids and carry them from the lymph system through the blood stream to...
Steroid hormones are classified into five major categories progestins mineralocorticoids glucocorticoids androgens and
Pregnenolone is derived from cholesterol and is the precursor of all other steroid hormones. For example, pregnenolone is coverted to progesterone by oxidation of the hydroxyl group to a ketone and isomerization of a double bond (see here). Synthesis of other steroid hormones from progesterone is shown in Figure 19.24. Note that 17-Hydroxyprogesterone is a branch point between synthesis of the glucocorticoids and the androgens. Thus, deficiency of 17-hydroxylase, the enzyme responsible for...
Tumor Suppressor Genes and Cancer Treatment
Ras genes encode a family of proteins (all of about 21 kilodaltons) with regions homologous to sequences in the ot subunit of G proteins (see here). Like the ot subunit, the Ras proteins bind guanine nucleotides. Normal Ras proteins possess a GTPase activity, as do G proteins, whereas most ras oncogene proteins lack this activity (by convention, the name of the gene is italicized, and the corresponding protein is not). The GTPase activity suggested that normal Ras proteins function like G...
Xanthine
Guanine + H2O < > Xanthine + NH3 (Guanine Deaminase) Hypoxanthine + O2 < > Xanthine + H2O2 (Xanthine Oxidase) Xanthine oxidase can oxidize xanthine further to uric acid, as well (Figure 22.7) Allopurinol, which is similar to hypoxanthine (see here), is used to treat gout because it inhibits xanthine oxidase, leading to accumulation of hypoxanthine and xanthine, both of which are more soluble and more readily excreted than uric acid (the causative agent of gout). See also Purine...
Fatty Acid Biosynthesis
Relationship of Fatty Acid Synthesis to Carbohydrate Metabolism (Figure 18.22) Acetyl-CoA from fatty acid and carbohydrate catabolism can be made into fatty acids, but not into glucose in animals. Early Studies of Fatty Acid Synthesis Biosynthesis of Palmitate from Acetyl-CoA (Figure 18.23) Synthesis of Malonyl-CoA (Diagram, Figure 18.24, Diagram) Acetyl-CoA carboxylase (biotin-containing - is primary regulatory enzyme of pathway) Same thioester linkage to fatty acid as Coenzyme A and same...
Creatine ATP Creatine Phosphate ADP catalyzed by Creatine Kinase
The latter reaction is strongly endergonic as written. However, the level of ATP is very high in mitochondria, so the reaction proceeds to the right. Creatine phosphate then diffuses from mitochondria to the myofibrils (see here), where it provides the energy for muscle contraction. High levels of ADP formed in the myofibrils during contraction favor the reverse reaction namely, resynthesis of ATP - at the expense of creatine phosphate cleavage to creatine. This example shows that one must...
See also Biological Fuel Liver Metabolism Ketogenesis from Chapter 18 Biochemistry of Neurotransmission from Chapter 21
One of the most important roles of the liver is to serve as a glucostat, monitoring and stabilizing blood glucose levels. To meet its internal energy needs, the liver can use a variety of fuel sources, including glucose, fatty acids, and amino acids. A primary role of liver is the synthesis of fuel components for use by other organs. Most of the low-molecular-weight metabolites that appear in the blood through digestion are taken up by the liver for this metabolic processing. Compounds...
Synthase I Glycogen Synthase D
Glycogen synthase D, like the other form of the enzyme (glycogen synthase I), catalyzes the addition of a glucose molecule (from UDP-glucose) in an ot 1,4 linkage to a growing glycogen chain. The two enzymes are identical except that glycogen synthase D arises from phosphorylation of glycogen synthase I by cAMP-dependent protein kinase or SPK (Figures 16.11 and 16.12). The phosphate group on glycogen synthase D causes it to be dependent on glucose-6-phosphate for activity. In the absence of...
Creatine ATP Creatine Phosphate ADP
The reaction is strongly endergonic as written. However, the level of ATP is very high in mitochondria, so the reaction proceeds to the right. Creatine phosphate then diffuses from mitochondria to the myofibrils, where it provides the energy for muscle contraction. High levels of ADP formed in the myofibrils (see here) during contraction favor the reverse reaction namely, resynthesis of ATP - at the expense of creatine phosphate cleavage to creatine. This example shows that one must consider...
Figure 2010 Structure of the proteasome
Baumeister from A. Lupas, J. M. Flanagan, T. Tamura, and W. Baumeister, Trends Biochem. Sci. (1997) 22 399-404, with permission from Elsevier Science. With few exceptions, the first step in amino acid degradation is removal of the ot-amino group. This modification, usually a transamination, can also be used to generate glutamate from a-ketoglutarate via the glutamate dehydrogenase reaction. The products of these reactions include deamination of the amino acid to the...
See also LDL Receptors Coated Pits Lipoprotein Complexes
Figure 18.10 Involvement of LDL receptors in cholesterol uptake and metabolism. Figure 18.10 Involvement of LDL receptors in cholesterol uptake and metabolism. The LDL lipoprotein complexes bind to receptor cells at specialized sites called LDL receptors. The receptors are clustered in structures called coated pits, which are abundant in the protein called clathrin. After binding to the LDL receptor, the LDL is internalized into the target cell by a process called receptor mediated endocytosis...
Utilization of Ammonia Biogenesis of Organic Nitrogen Figure 207
Glutamate Dehydrogenase Reductive Amination of oi-ketoglutarate (Diagram 1, 2) Glutamine Synthetase Generation of Biologically Active Amide Nitrogen (Diagram) Regulation of Glutamine Synthetase (Diagram, Figure 20.9) Asparagine Synthetase A Similar Amidation Reaction (Diagram) Carbamoyl Phosphate Synthetase Generation of an Intermediate for Arginine and Pyrimidine Synthesis (Diagram) The Nitrogen Economy Aspects of Amino Acid Synthesis and Degradation Metabolic Consequences of the Absence of...
H2
See also Neurotransmitters and Biological Regulators, Biochemistry of Neurotransmission Tyrosine The term catecholamine comes from the aromatic dialcohol, catechol. The most common catecholamines are epinephrine, norepinephrine, dopamine, and dihydroxyphenylalanine (L-Dopa). Catecholamine analogs, such as mescaline and amphetamine have potent psychopharmacological properties. Figure 21.32 depicts the pathway to catecholamines from tyrosine. See also Aromatic Amino Acid Utilization,...
See also Hormone Action Hormone Mechanisms of Action Hormone Hierarchy of Action Receptors with Protein Kinase Activity
Thyroid Hormone Receptor Resource Figure 12.13 Signal transduction pathway involving adenylate cyclase. i Figure 12.13 Signal transduction pathway involving adenylate cyclase. i The insulin receptor (Figure 23. ) is a glycoprotein with an ot2. 2 tetrameric structure, stabilized by disulfide bonds. Both the ot chain (735 residues) and the fi chain (620 residues) are translated from a single mRNA, giving a polypeptide chain that then undergoes proteolytic processing. The ot chain, which is...
See also Action of Insulin from Chapter 23 Gluconeogenesis Control of Fatty Acid Synthesis Hormonal Regulation of Fuel
PEPCK is an enzyme of gluconeogenesis. It catalyzes conversion of the 4-carbon compound, oxaloacetate, to phosphoenolpyruvate (PEP), releasing CO2. The reaction requires energy input from GTP and produces GDP. Oxaloacetate + GTP < > PEP + CO2 + GDP For PEPCK to function in gluconeogenesis, oxaloacetate produced in the pyruvate carboxylase reaction in the mitochondria, must be transported to the cytoplasm. PEPCK is not under any known allosteric control. Activity of the enzyme is regulated...
AcetylCoA inhibits Pyruvate kinase and activates Pyruvate Carboxylase
Other control points on the two pathways are shown in Figure 16.6 The major allosteric regulatory factor of the two pathways is Fructose 2,6 bisphosphate. Note in Figure 16.7 that PFK-2 and Fructose 2,6-bisphosphatase are on the same peptide and are affected differently by phosphorylation see below . Interconversion of PFK-2 and Fructose 2,6-bisphosphatase depends on the level of cAMP which is stimulated by glucagon and epinephrine and is inhibited by insulin . Increasing cAMP glucagon...
See also Oxygen Binding by Heme Proteins Oxygen Binding by Myoglobin Oxygen Binding by Hemoglobin Hemoglobin Allostery
Figure 7.3 Comparison of myoglobin and hemoglobin. Li Figure 7.3 Comparison of myoglobin and hemoglobin. Li Figure 6.1 Three-dimensional folding of the protein myoglobin. Figure 6.1 Three-dimensional folding of the protein myoglobin. Myoglobin Hemoglobin Structure - The myoglobin-hemoglobin family of proteins employs Fe II for O2 binding. Throughout the myoglobin-hemoglobin family, the iron is chelated by a tetrapyrrole ring system called protoporphyrin IX, one of a large class of porphyrin...
Xanthosine Monophosphate
Inosine Monophosphate IMP NAD H2O lt gt Xanthosine Monophosphate XMP NADH Subsequently, XMP is converted to GMP by the enzyme XMP aminase Figure 22.6 . See also De Novo Biosynthesis of Purine Nucleotides AMP Deaminase is an enzyme in purine catabolism that deaminates AMP to form IMP and ammonia, as follows See also Figure 22.7, Purine Degradation Figure 22.7 Catabolism of purine nucleotides to uric acid. Figure 22.7 Catabolism of purine nucleotides to uric acid. Figure 22.7 shows pathways of...
See also Glycogen Synthase Glycogen Biosynthesis Glycogen Synthase D cAMPDependent Protein Kinase Kinase Cascade
Glycogen synthesis and breakdown are controlled tightly by hormonal action. These involve regulatory kinase cascades, as depicted in Figure 13.18 for glycogen breakdown. Like gluconeogenesis glycolysis, glycogen synthesis breakdown is reciprocally regulated. For example, epinephrine inhibits glycogen synthesis at the same time as it promotes glycogen breakdown. Glycogen synthase is the primary regulatory enzyme in glycogen synthesis. Like glycogen phosphorylase, the enzyme that breaks down...
See also Citrate Shuttle
Malic Enzyme officially named malate dehydrogenase-decarboxylating NADP catalyzes the reaction below. Pyruvate HCO3- NADPH H lt gt L-Malatt NAD H2O This important anaplerotic reaction provides a means of replenishing L-malate in the citric acid cycle Figure 14.18 and it also plays an important role in the citrate shuttle Figure 18.31 . See also Citric Acid Cycle, Anaplerotic Reaction, Citrate Shuttle Figure 14.18 Major biosynthetic roles of some citric acid cycle intermediates. Li Figure 14.18...
See also Phosphorolysis Glycogen phosphorylase Figure 1318 Kinase Cascade Figure 1316 Figure 1317 Polysaccharides
Glycosidic bonds between monosaccharides give rise to oligosaccharides and polysaccharides. The simplest oligosaccharides, the disaccharides, include compounds such as sucrose and lactose, which are referred to as sugars like the monosaccharides . Other common disaccharides include trehalose, maltose, gentiobiose, and cellobiose. Four features distinguish disaccharides from each other 1. The two specific sugar monomers and their stereoconfigurations 2. The carbons involved in the linkage 3. The...
