Examples of Metabolism Anabolism and Catabolism
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Amphibolic Nature of Krebs Cycle
Amphibolic nature of Krebs Cycle How what we are is what we eat • In aerobic organisms, the citric acid cycle is an amphibolic pathway, one that serves in both catabolic and anabolic processes. • Since the citric acid does both synthesis (anabolic) and breakdown (catabolic) activities, it is called an amphibolic pathway • The citric acid cycle is amphibolic (i.e it is both anabolic and catabolic in its function). • It is said to be an AMPHIBOLIC pathway, because it functions in both degradative or catabolic and biosynthetic or anabolic reactions (amphi = both) A central metabolic pathway or amphibolic pathway is a set of reactions which permit the interconversion of several metabolites, and represents the end of the catabolism and the beginning of anabolism • The KREBS CYCLE or citric acid cycle is a series of reactions that degrades acetyl CoA to yield carbon dioxide, and energy, which is used to produce NADH, H+ and FADH. • The KREBS CYCLE connects the catabolic pathways that begin with the digestion and degradation of foods in stages 1 and 2 with the oxidation of substrates in stage 3 that generates most of the energy for ATP synthesis. • The citric acid cycle is the final common pathway in the oxidation of fuel molecules. In stage 3 of metabolism, citric acid is a final common catabolic intermediate in the form of acetylCoA. • This is why the citric acid cycle is called a central metabolic pathway. Anaplerosis and Cataplerosis Anaplerosis is a series of enzymatic reactions in which metabolic intermediates enter the citric acid cycle from the cytosol. Cataplerosis is the opposite, a process where intermediates leave the citric acid cycle and enter the cytosol. -
The Citric Acid Cycle the Catabolism of Acetyl-Coa
Al-Sham Private University Faculty Of Pharmacy The Citric Acid Cycle The Catabolism of Acetyl-CoA Lecturer Prof. Abboud Al-Saleh 1 Prof.Abboud AL-Saleh 10/1/2018 BIOMEDICAL IMPORTANCE • 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. • TCA 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 cycle. 2 Prof.Abboud AL-Saleh 10/1/2018 • TCA also has a central role in gluconeogenesis, lipogenesis, and interconversion of amino acids. Many of these processes occur in most tissues, but the liver is the only tissue in which all occur to a significant extent. • The repercussions are therefore profound when, for example, large numbers of hepatic cells are damaged as in acute hepatitis or as in cirrhosis. • Very few, if any, genetic abnormalities of TCA enzymes have been reported; such abnormalities would be incompatible with life or normal development 3 Prof.Abboud AL-Saleh 10/1/2018 Summary • The cycle starts with reaction between the acetyl moiety of acetyl-CoA and the four-carbon dicarboxylic acid oxaloacetate, forming a six-carbon tricarboxylic acid, citrate. • In the subsequent reactions, two molecules of CO2 are released and oxaloacetate is regenerated (Figure). • Only a small quantity of oxaloacetate is needed for the oxidation of a large quantity of acetyl-CoA. • oxaloacetate may be considered to play a catalytic role. -
Catabolism Iii
Nitrogen Catabolism Glycogenolysis Protein Fat catabolism Catabolism Fatty Acid Amino-acid GlycolysisDegradation catabolism Pyruvate Oxidation Krebs' Cycle Phosphorylation Oxidative CATABOLISM III: Digestion and Utilization of Proteins • Protein degradation • Protein turnover – The ubiquitin pathway – Protein turnover is tightly regulated • Elimination of nitrogen – By fish, flesh and fowl – How is the N of amino acids liberated and eliminated? • How are amino acids oxidized for energy 1 Protein Catabolism Sources of AMINO ACIDS: •Dietary amino acids that exceed body’s protein synthesis needs •Excess amino acids from protein turnover (e.g., proteolysis and regeneration of proteins) •Proteins in the body can be broken down (muscle wasting) to supply amino acids for energy when carbohydrates are scarce (starvation, diabetes mellitus). •Carnivores use amino acids for energy more than herbivores, plants, and most microorganisms Protein Catabolism The Digestion Pathway • Pro-enzymes are secreted (zymogens) and the environment activates them by specific proteolysis. • Pepsin hydrolyzes protein into peptides in the stomach. • Trypsin and chymotrypsin hydrolyze proteins and larger peptides into smaller peptides in the small intestine. • Aminopeptidase and carboxypeptidases A and B degrade peptides into amino acids in the small intestine. 2 Protein Catabolism The Lysosomal Pathway • Endocytosis, either receptor-mediated, phagocytosis, or pinocytosis engulfs extra- cellular proteins into vesicles. • These internal vesicles fuse as an early endosome. • This early endosome is acidified by the KFERQ Substrates vATPase (“v” for vesicular). • Components that are recycled, like receptors, HSPA8 are sequestered in smaller vesicles to create Co-chaperones the multivesicular body (MVB), sometimes called a late endosome. • If set for degradation, it will fuse with a KFERQ primary lysosome (red) which contains many cathepsin-type proteases. -
Fatty Acid Biosynthesis
BI/CH 422/622 ANABOLISM OUTLINE: Photosynthesis Carbon Assimilation – Calvin Cycle Carbohydrate Biosynthesis in Animals Gluconeogenesis Glycogen Synthesis Pentose-Phosphate Pathway Regulation of Carbohydrate Metabolism Anaplerotic reactions Biosynthesis of Fatty Acids and Lipids Fatty Acids contrasts Diversification of fatty acids location & transport Eicosanoids Synthesis Prostaglandins and Thromboxane acetyl-CoA carboxylase Triacylglycerides fatty acid synthase ACP priming Membrane lipids 4 steps Glycerophospholipids Control of fatty acid metabolism Sphingolipids Isoprene lipids: Cholesterol ANABOLISM II: Biosynthesis of Fatty Acids & Lipids 1 ANABOLISM II: Biosynthesis of Fatty Acids & Lipids 1. Biosynthesis of fatty acids 2. Regulation of fatty acid degradation and synthesis 3. Assembly of fatty acids into triacylglycerol and phospholipids 4. Metabolism of isoprenes a. Ketone bodies and Isoprene biosynthesis b. Isoprene polymerization i. Cholesterol ii. Steroids & other molecules iii. Regulation iv. Role of cholesterol in human disease ANABOLISM II: Biosynthesis of Fatty Acids & Lipids Lipid Fat Biosynthesis Catabolism Fatty Acid Fatty Acid Degradation Synthesis Ketone body Isoprene Utilization Biosynthesis 2 Catabolism Fatty Acid Biosynthesis Anabolism • Contrast with Sugars – Lipids have have hydro-carbons not carbo-hydrates – more reduced=more energy – Long-term storage vs short-term storage – Lipids are essential for structure in ALL organisms: membrane phospholipids • Catabolism of fatty acids –produces acetyl-CoA –produces reducing -
Regulation of Energy Substrate Metabolism in Endurance Exercise
International Journal of Environmental Research and Public Health Review Regulation of Energy Substrate Metabolism in Endurance Exercise Abdullah F. Alghannam 1,* , Mazen M. Ghaith 2 and Maha H. Alhussain 3 1 Lifestyle and Health Research Center, Health Sciences Research Center, Princess Nourah bInt. Abdulrahman University, Riyadh 84428, Saudi Arabia 2 Faculty of Applied Medical Sciences, Laboratory Medicine Department, Umm Al-Qura University, Al Abdeyah, Makkah 7607, Saudi Arabia; [email protected] 3 Department of Food Science and Nutrition, College of Food and Agriculture Sciences, King Saud University, Riyadh 11451, Saudi Arabia; [email protected] * Correspondence: [email protected] Abstract: The human body requires energy to function. Adenosine triphosphate (ATP) is the cellular currency for energy-requiring processes including mechanical work (i.e., exercise). ATP used by the cells is ultimately derived from the catabolism of energy substrate molecules—carbohydrates, fat, and protein. In prolonged moderate to high-intensity exercise, there is a delicate interplay between carbohydrate and fat metabolism, and this bioenergetic process is tightly regulated by numerous physiological, nutritional, and environmental factors such as exercise intensity and du- ration, body mass and feeding state. Carbohydrate metabolism is of critical importance during prolonged endurance-type exercise, reflecting the physiological need to regulate glucose homeostasis, assuring optimal glycogen storage, proper muscle fuelling, and delaying the onset of fatigue. Fat metabolism represents a sustainable source of energy to meet energy demands and preserve the ‘limited’ carbohydrate stores. Coordinated neural, hormonal and circulatory events occur during prolonged endurance-type exercise, facilitating the delivery of fatty acids from adipose tissue to the Citation: Alghannam, A.F.; Ghaith, working muscle for oxidation. -
Citric Acid Cycle
CHEM464 / Medh, J.D. The Citric Acid Cycle Citric Acid Cycle: Central Role in Catabolism • Stage II of catabolism involves the conversion of carbohydrates, fats and aminoacids into acetylCoA • In aerobic organisms, citric acid cycle makes up the final stage of catabolism when acetyl CoA is completely oxidized to CO2. • Also called Krebs cycle or tricarboxylic acid (TCA) cycle. • It is a central integrative pathway that harvests chemical energy from biological fuel in the form of electrons in NADH and FADH2 (oxidation is loss of electrons). • NADH and FADH2 transfer electrons via the electron transport chain to final electron acceptor, O2, to form H2O. Entry of Pyruvate into the TCA cycle • Pyruvate is formed in the cytosol as a product of glycolysis • For entry into the TCA cycle, it has to be converted to Acetyl CoA. • Oxidation of pyruvate to acetyl CoA is catalyzed by the pyruvate dehydrogenase complex in the mitochondria • Mitochondria consist of inner and outer membranes and the matrix • Enzymes of the PDH complex and the TCA cycle (except succinate dehydrogenase) are in the matrix • Pyruvate translocase is an antiporter present in the inner mitochondrial membrane that allows entry of a molecule of pyruvate in exchange for a hydroxide ion. 1 CHEM464 / Medh, J.D. The Citric Acid Cycle The Pyruvate Dehydrogenase (PDH) complex • The PDH complex consists of 3 enzymes. They are: pyruvate dehydrogenase (E1), Dihydrolipoyl transacetylase (E2) and dihydrolipoyl dehydrogenase (E3). • It has 5 cofactors: CoASH, NAD+, lipoamide, TPP and FAD. CoASH and NAD+ participate stoichiometrically in the reaction, the other 3 cofactors have catalytic functions. -
Amino Acid Catabolism: Urea Cycle the Urea Bi-Cycle Two Issues
BI/CH 422/622 OUTLINE: OUTLINE: Protein Degradation (Catabolism) Digestion Amino-Acid Degradation Inside of cells Urea Cycle – dealing with the nitrogen Protein turnover Ubiquitin Feeding the Urea Cycle Activation-E1 Glucose-Alanine Cycle Conjugation-E2 Free Ammonia Ligation-E3 Proteosome Glutamine Amino-Acid Degradation Glutamate dehydrogenase Ammonia Overall energetics free Dealing with the carbon transamination-mechanism to know Seven Families Urea Cycle – dealing with the nitrogen 1. ADENQ 5 Steps 2. RPH Carbamoyl-phosphate synthetase oxidase Ornithine transcarbamylase one-carbon metabolism Arginino-succinate synthetase THF Arginino-succinase SAM Arginase 3. GSC Energetics PLP uses Urea Bi-cycle 4. MT – one carbon metabolism 5. FY – oxidases Amino Acid Catabolism: Urea Cycle The Urea Bi-Cycle Two issues: 1) What to do with the fumarate? 2) What are the sources of the free ammonia? a-ketoglutarate a-amino acid Aspartate transaminase transaminase a-keto acid Glutamate 1 Amino Acid Catabolism: Urea Cycle The Glucose-Alanine Cycle • Vigorously working muscles operate nearly anaerobically and rely on glycolysis for energy. a-Keto acids • Glycolysis yields pyruvate. – If not eliminated (converted to acetyl- CoA), lactic acid will build up. • If amino acids have become a fuel source, this lactate is converted back to pyruvate, then converted to alanine for transport into the liver. Excess Glutamate is Metabolized in the Mitochondria of Hepatocytes Amino Acid Catabolism: Urea Cycle Excess glutamine is processed in the intestines, kidneys, and liver. (deaminating) (N,Q,H,S,T,G,M,W) OAA à Asp Glutamine Synthetase This costs another ATP, bringing it closer to 5 (N,Q,H,S,T,G,M,W) 29 N 2 Amino Acid Catabolism: Urea Cycle Excess glutamine is processed in the intestines, kidneys, and liver. -
Lecture 9: Citric Acid Cycle/Fatty Acid Catabolism
Metabolism Lecture 9 — CITRIC ACID CYCLE/FATTY ACID CATABOLISM — Restricted for students enrolled in MCB102, UC Berkeley, Spring 2008 ONLY Bryan Krantz: University of California, Berkeley MCB 102, Spring 2008, Metabolism Lecture 9 Reading: Ch. 16 & 17 of Principles of Biochemistry, “The Citric Acid Cycle” & “Fatty Acid Catabolism.” Symmetric Citrate. The left and right half are the same, having mirror image acetyl groups (-CH2COOH). Radio-label Experiment. The Krebs Cycle was tested by 14C radio- labeling experiments. In 1941, 14C-Acetyl-CoA was used with normal oxaloacetate, labeling only the right side of drawing. But none of the label was released as CO2. Always the left carboxyl group is instead released as CO2, i.e., that from oxaloacetate. This was interpreted as proof that citrate is not in the 14 cycle at all the labels would have been scrambled, and half of the CO2 would have been C. Prochiral Citrate. In a two-minute thought experiment, Alexander Ogston in 1948 (Nature, 162: 963) argued that citrate has the potential to be treated as chiral. In chemistry, prochiral molecules can be converted from achiral to chiral in a single step. The trick is an asymmetric enzyme surface (i.e. aconitase) can act on citrate as through it were chiral. As a consequence the left and right acetyl groups are not treated equivalently. “On the contrary, it is possible that an asymmetric enzyme which attacks a symmetrical compound can distinguish between its identical groups.” Metabolism Lecture 9 — CITRIC ACID CYCLE/FATTY ACID CATABOLISM — Restricted for students enrolled in MCB102, UC Berkeley, Spring 2008 ONLY [STEP 4] α-Keto Glutarate Dehydrogenase. -
Cellular Respiration Cellular
BIOLOGY Chapter 8: pp. 133-149 10th Edition Sylvia S. Sylvia Cellular Respiration Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Mader e– NADH NADH e– Insert figure 8.2 here e– e– NADH and Cytoplasm e– FADH 2 Mitochondrion e– – e Glycolysis Electron transport Preparatory reaction Citric acid chain and glucose pyruvate cycle chemiosmosis 2 ADP 2 ADP 4 ADP 4 ATP total 2 ATP net gain 2 ADP 2 ATP 32 ADP 32 ATP or 34 or 34 PowerPoint® Lecture Slides are prepared by Dr. Isaac Barjis, Biology Instructor 1 Copyright © The McGraw Hill Companies Inc. Permission required for reproduction or display Outline Cellular Respiration NAD+ and FAD Phases of Cellular Respiration Glycolysis Fermentation Preparatory Reaction Citric Acid Cycle Electron Transport System Metabolic Pool Catabolism Anabolism 2 Cellular Respiration A cellular process that breaks down carbohydrates and other metabolites with the concomitant buildup of ATP Consumes oxygen and produces carbon dioxide (CO2) Cellular respiration is aerobic process. Usually involves breakdown of glucose to CO2 and water Energy extracted from glucose molecule: Released step-wise Allows ATP to be produced efficiently Oxidation-reduction enzymes include NAD+ and FAD as coenzymes 3 Glucose Breakdown: Summary Reaction Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Oxidation C6H12O6 + 6O2 6CO2 + 6HCO2 + energy glucose Reduction Electrons are removed from substrates and received by oxygen, which combines -
The Postabsorptive State
Chapter 26 Lecture Outline See separate PowerPoint slides for all figures and tables pre- inserted into PowerPoint without notes. Copyright © McGraw-Hill Education. Permission required for reproduction or display. 1 Introduction • Nutrition is the starting point and the basis for all human form and function – The source of fuel that provides energy for all biological work – The source of raw materials for replacement of worn- out biomolecules and cells • Metabolism is the chemical change that lies at the foundation of form and function 26-2 Nutrition • Expected Learning Outcomes – Describe some factors that regulate hunger and satiety. – Define nutrient and list the six major categories of nutrients. – State the function of each class of macronutrients, the approximate amounts required in the diet, and some major dietary sources of each. – Name the blood lipoproteins, state their functions, and describe how they differ from each other. – Name the major vitamins and minerals required by the body and the general functions they serve. 26-3 Body Weight and Energy Balance • Weight—determined by the body’s energy balance – If energy intake and output are equal, body weight is stable – Gain weight if intake exceeds output – Lose weight if output exceeds intake – Weight seems to have a stable, homeostatic set point • Varies from person to person • Combination of heredity and environmental influences – 30% to 50% of variation in human weight is hereditary – Environmental factors such as eating and exercise habits account for the rest of the variation -
Biochemistry Anabolism of Lipids
Paper : 05 Metabolism of Lipids Module: 12 Anabolism of Lipids Principal Investigator Dr. Sunil Kumar Khare, Professor, Department of Chemistry, IIT-Delhi Dr. Vijaya Khader Dr. MC Varadaraj Paper Coordinator and Dr. Suaib Luqman, Scientist (CSIR-CIMAP) Content Writer & Assistant Professor (AcSIR) CSIR -CIMAP, Lucknow Content Reviewer Prof. Prashant Mishra, Professor, Department of Biochemical Engineering and Biotechnology, IIT-Delhi 1 METABOLISM OF LIPIDS Biochemistry Anabolism of Lipids DESCRIPTION OF MODULE Subject Name Biochemistry Paper Name 05 Metabolism of Lipids Module Name/Title 12 Lipids-Anabolism 2 METABOLISM OF LIPIDS Biochemistry Anabolism of Lipids 1. Objectives To understand the anabolism of lipids What are the implications of lipid anabolism 2. Concept Map 3 METABOLISM OF LIPIDS Biochemistry Anabolism of Lipids 4 METABOLISM OF LIPIDS Biochemistry Anabolism of Lipids 3. Description Anabolism is the word derived from the Greek (Ana-upward and Bolism-to throw) meaning a process that have a propensity to build up tissues and organs. It is an array of metabolic pathways that assemble molecules from smaller units and the process engender differentiation and growth of cells and augmentation in body size (e.g. growth and mineralization of bone and increase in muscle mass). The reactions in anabolism entail and utilize energy released by catabolism to synthesize complex molecules which further employed to form cellular 5 METABOLISM OF LIPIDS Biochemistry Anabolism of Lipids structures from simple and small precursors that act as building blocks. Numerous anabolic processes are power- driven by the hydrolysis of adenosine triphosphate (ATP). Following are the fundamental defined stages of anabolism. 1. Assembly of precursors such as fatty acids, amino acids, isoprenoids, monosaccharides and nucleotides. -
ANABOLISM III: Biosynthesis Amino Acids & Nucleotides
BI/CH 422/622 ANABOLISM OUTLINE: Photosynthesis Carbohydrate Biosynthesis in Animals Biosynthesis of Fatty Acids and Lipids Biosynthesis of Amino Acids and Nucleotides Nitrogen fixation nitrogenase Nitrogen assimilation Glutamine synthetase Glutamate synthase Amino-acid Biosynthesis non-essential essential Nucleotide Biosynthesis RNA precursors purines pyrimidines DNA precursors deoxy-nucleotides Biosynthesis of secondary products of amino acids ANABOLISM III: Biosynthesis Amino Acids & Nucleotides Dr. Kornberg: Lecture 04.26.17 (0:00-5:06) 5 min 1 Biosynthesis Amino Acids & Nucleotides How are Ribonucleic Acid Precursors So far: converted to Deoxyribonucleic Acid GMPàGDPàGTP Precursors? ….....and how is dTTP made? AMPàADPàATP 2’C-OH bond is directly reduced to 2’-H UMPàUDPàUTPà bond …without activating the carbon for CDPßCTP dehydration, etc.! catalyzed by ribonucleotide reductase Specific kinases, Non-specific kinase, e.g., UMP kinase, nucleoside GMP kinase, diphosphate kinase Very unique enzyme in all of biochemistry – use of free Adenylate kinase (works on both oxy- and radicals etc. deoxy-ribose GDPàdGDP nucleosides) Mechanism: Two H atoms are donated ADPàdADP by NADPH and carried by thioredoxin or glutaredoxin to the active site. UDPàdUDP –Substrates are the NDPs and the products CDPàdCDP are dNDP. Biosynthesis Amino Acids & Nucleotides Source of Reducing Structure of Ribonucleotide Reductase a2 are regulatory Electrons for and half the Ribonucleotide catalytic site; need to be reduced. Reductase b 2 are the other half (a b ) of the active site, 2 2 and the free- radical generators • NADPH serves as the electron donor. • Funneled through glutathione or JoAnne Stubbe thioredoxin pathways (1946– ) 2 •Most forms of enzyme have two catalytic/ regulatory subunits and two radical- generating subunits.