Principles of Biochemistry, Volume 2 - A. Lehninger 1985
Bioenergetics and Metabolism
Living organisms participate in the global carbon and oxygen cycles.
There is a nitrogen cycle in the biosphere
Metabolic pathways are sequences of reactions catalyzed by multienzyme systems
Metabolism encompasses catabolic and anabolic pathways (degradation and synthesis processes)
Catabolic pathways converge to yield only a small number of end products
Biosynthetic (anabolic) pathways diverge to yield a wide variety of products
Energy is transferred from catabolic reactions to anabolic reactions via ATP
NADPH transfers energy in the form of reducing power
Cellular metabolism is an economical, strictly regulated process
The regulation of metabolic pathways occurs at three levels
Metabolism: A General Overview
Metabolism: An Overview
Metabolic pathways can be identified through direct experiments
Intermediary metabolic steps can be identified using mutant organisms
Isotope labeling is a highly effective method for studying metabolism.
Various metabolic pathways may be localized in different compartments of the cell
The ATP Cycle and Cellular Bioenergetics
First and Second Laws of Thermodynamics
ATP Cycle and Cellular Bioenergetics
The ATP Cycle and Cellular Bioenergetics
The change in standard free energy of a chemical reaction can be calculated
ATP Cycle and Cellular Bioenergetics
Chemical reactions are characterized by a specific value of ∆G0'
The ATP Cycle and Cellular Bioenergetics
The values of ∆G0' and ∆G differ, and this distinction is of great significance
Changes in the standard free energy of chemical reactions are additive
The chemical properties of ATP are well established
ATP Cycle and Cellular Bioenergetics
Characteristic value of the standard free energy of ATP
The ATP Cycle and Cell Bioenergetics
Why is the standard free energy of ATP hydrolysis relatively large?
ATP Cycle and Cellular Bioenergetics
ATP serves as a common intermediate in group transfer reactions involving phosphate
The ATP Cycle and Cellular Bioenergetics
The breakdown of glucose into lactate produces two ultra-high-energy phosphorylated compounds
ATP Cycle and Cellular Bioenergetics
ATP is used to provide energy for muscle contraction
The ATP Cycle and Cellular Bioenergetics
Creatine phosphate in muscles serves as a reservoir for high-energy phosphate groups
ATP Cycle and Cellular Bioenergetics
ATP also supplies energy for active transport across membranes
The ATP Cycle and Cellular Bioenergetics
ATP can also be cleaved into AMP and pyrophosphate.
In addition to ATP, there are other high-energy nucleotide 5'-triphosphates
ATP Cycle and Cellular Bioenergetics
The ATP system operates in a stationary-dynamic mode
Glycolysis: The Central Pathway of Glucose Catabolism
Glycolysis is a central metabolic pathway in the majority of organisms
Glycolysis as the Central Pathway of Glucose Catabolism
ATP Synthesis Coupled to Glycolysis
Glycolysis: The Central Pathway of Glucose Catabolism
Glycolysis products still retain a significant amount of free energy
Glycolysis consists of two stages
Phosphorylated intermediates are formed during glycolysis
The first phase of glycolysis concludes with the cleavage of the carbon skeleton of glucose
Energy is stored during the second stage of glycolysis
Pathways leading from glycogen and other carbohydrates to the central glycolytic pathway
Other simple sugars can also enter the glycolytic pathway
Disaccharides must first undergo hydrolysis to monosaccharides
The entry of glucose residues into the glycolytic pathway is regulated
Glycolysis as the Central Pathway of Glucose Catabolism
The interconversions of phosphorylase $ and phosphorylase $ are ultimately regulated by hormones
Glycolysis: The Central Pathway of Glucose Catabolism
The sequence of glycolytic reactions itself is regulated at two primary control points
How can regulated steps of glycolysis be identified in intact cells?
Alcoholic fermentation differs from glycolysis only in its final stages
The oxidation of glucose to CO2 and H2O releases significantly more energy than glycolysis does.
Pyruvate must first be oxidized to acetyl-CoA and CO2
The citric acid cycle is not a linear, but a closed pathway
How did the very concept of the citric acid cycle originate?
The citric acid cycle consists of eight stages
General Characteristics of the Cycle
What is the significance of the citric acid cycle?
Application of Isotope Tracer Methods to the Study of the Citric Acid Cycle
The conversion of pyruvate to acetyl-CoA is regulated
The citric acid cycle is regulated
Citric Acid Cycle
The glyoxylate cycle is a modification of the citric acid cycle
The Citric Acid Cycle
Alternative Pathways of Glucose Catabolism: The Pentose Phosphate Pathway
The alternative pathway for the conversion of glucose into glucuronic and ascorbic acids
Electron Transport, Oxidative Phosphorylation, and the Regulation of ATP Synthesis
Electron transfer from substrates to oxygen serves as the energy source for ATP
Electron Transport, Oxidative Phosphorylation, and Regulation of ATP Synthesis
Electron transport and oxidative phosphorylation take place in the inner mitochondrial membrane.
Electron Transport, Oxidative Phosphorylation, and the Regulation of ATP Synthesis
Electron transfer reactions are oxidation-reduction reactions
Electron Transport, Oxidative Phosphorylation, and Regulation of ATP Synthesis
Each conjugate redox pair is characterized by a specific standard potential
Electron transport is accompanied by changes in free energy
The electron transport chain includes a large number of carriers
Pyridine nucleotides perform a collector function
Electron Transport, Oxidative Phosphorylation, and the Regulation of ATP Synthesis
NADH dehydrogenase accepts electrons from NADH
Ubiquinone is a fat-soluble quinone
Electron Transfer, Oxidative Phosphorylation, and Regulation of ATP Synthesis
Cytochromes are hemoproteins that mediate electron transfer
Electron Transport, Oxidative Phosphorylation, and Regulation of ATP Synthesis
Incomplete reduction of oxygen leads to cellular damage
Electron carriers always operate in a specific sequence
The energy released during electron transport is conserved through oxidative phosphorylation.
Electron transport, oxidative phosphorylation, and the regulation of ATP synthesis
The enzyme catalyzing ATP synthesis was isolated and reconstituted
Electron Transport, Oxidative Phosphorylation, and Regulation of ATP Synthesis
How is the redox energy of electron transport coupled to ATP synthase?
Electron Transport, Oxidative Phosphorylation, and the Regulation of ATP Synthesis
Electron Transport, Oxidative Phosphorylation, and Regulation of ATP Synthesis
Electron transfer energy is also utilized for other purposes
Bacterial cells and chloroplasts also contain electron transport chains that transport H+ ions
The inner mitochondrial membrane contains specific transport systems
Shuttle systems are involved in the oxidation of extramitochondrial NADH
Complete oxidation of a glucose molecule yields 38 ATP molecules
Electron transport, oxidative phosphorylation, and regulation of ATP synthesis
The energy charge serves as another indicator of the cellular energy status
Electron Transport, Oxidative Phosphorylation, and the Regulation of ATP Synthesis
Electron Transport, Oxidative Phosphorylation, and Regulation of ATP Synthesis
Cells also contain other enzymes that utilize oxygen as an electron acceptor.
Oxidation of Fatty Acids in Animal Tissues
Fatty acids are activated and oxidized in the mitochondria
The transport of fatty acids into the mitochondria consists of three stages
Fatty Acid Oxidation in Animal Tissues
Fatty acid oxidation involves two stages
The first stage of saturated fatty acid oxidation consists of four steps
During the first stage of fatty acid oxidation, acetyl-CoA and ATP are produced
In the second stage of fatty acid oxidation, acetyl-CoA is oxidized via the citric acid cycle
The oxidation of unsaturated fatty acids requires two additional enzymatic steps
Oxidation of Fatty Acids with an Odd Number of Carbon Atoms
Hypoglycin (a toxic substance produced by certain plants) inhibits fatty acid oxidation
Formation of Ketone Bodies in the Liver and Their Oxidation in Other Organs
Regulation of Fatty Acid Oxidation and Ketone Body Formation
Oxidation of Fatty Acids in Animal Tissues
Oxidative Degradation of Amino Acids. The Urea Cycle
The transfer of $\alpha$-amino groups is catalyzed by transaminases
Ammonia is produced from glutamate
There are 20 different pathways for the degradation of amino acid carbon skeletons
Ten amino acids are converted into acetyl-CoA as a result of degradation.
Inherited Disorders of Phenylalanine Catabolism
Five amino acids are converted to α-ketoglutarate
Three amino acids are converted into succinyl-CoA
Fumarate is formed from phenylalanine and tyrosine
Some amino acids can be converted into glucose, while others are converted into ketone bodies.
Ammonia is transported to the liver from many peripheral tissues in the form of glutamine
Oxidative Degradation of Amino Acids. Urea Cycle
Ammonia is transported from muscles to the liver in the form of alanine
Oxidative Degradation of Amino Acids. The Urea Cycle
Glutaminase is involved in the excretion of ammonia
Urea is produced in the urea cycle
The urea cycle involves a series of complex stages
The Energetic Cost of Urea Synthesis
Genetic defects affecting the urea cycle cause ammonia accumulation in the blood
Birds, snakes, and lizards excrete uric acid.
Biosynthesis of Carbohydrates in Animal Tissues
Carbohydrate Biosynthesis in Animal Tissues
The gluconeogenesis pathway comprises seven steps shared with glycolysis.
Biosynthesis of Carbohydrates in Animal Tissues
A bypass pathway is required to convert pyruvate into phosphoenolpyruvate
The third bypass pathway is the route leading from glucose-6-phosphate to free glucose.
Gluconeogenesis requires a significant energy input
Carbohydrate Biosynthesis in Animal Tissues
Reciprocal Regulation of Gluconeogenesis and Glycolysis
Biosynthesis of Carbohydrates in Animal Tissues
Intermediates of the citric acid cycle also serve as precursors for glucose
Most amino acids are classified as glucogenic
Gluconeogenesis occurs during the recovery period following muscular activity
Particularly active gluconeogenesis is characteristic of ruminants.
Alcohol Inhibits Gluconeogenesis
Futile Cycles in Carbohydrate Metabolism
The pathway of glycogen biosynthesis differs from that of its breakdown
Biosynthesis of carbohydrates in animal tissues
Glycogen synthase and glycogen phosphorylase are reciprocally regulated
Biosynthesis of Carbohydrates in Animal Tissues
There are genetic disorders associated with impaired glycogen metabolism.
Lactose synthesis is subject to specific regulation
Lipid Biosynthesis
The pathway of fatty acid biosynthesis differs from that of their oxidation
Malonyl-CoA is formed from acetyl-CoA
The synthase system catalyzing fatty acid formation features seven active sites
The sulfhydryl groups of fatty acid synthase initially interact with acyl groups.
The addition of each two-carbon unit proceeds in four stages
Palmitic acid serves as a precursor for other long-chain fatty acids.
Regulation of Fatty Acid Biosynthesis
The biosynthesis of triacylglycerols and glycerophospholipids begins with common precursors.
The biosynthesis of triacylglycerols is hormonally regulated
Triacylglycerols as an Energy Source for Certain Hibernating Animals
Phosphatidylcholine is formed via two different pathways
Polar lipids integrate into cell membranes
Genetic Defects in Lipid Metabolism
Numerous lysosomal storage diseases exist
Cholesterol and other steroids are also synthesized from two-carbon precursors
Isopentenyl pyrophosphate serves as a precursor for many fat-soluble biomolecules.
Biosynthesis of Amino Acids and Nucleotides
Certain amino acids must be obtained from the diet
A common biosynthetic pathway leads to glutamate, glutamine, and proline
Alanine, aspartate, and asparagine are also synthesized from central metabolites
Tyrosine is synthesized from the essential amino acid phenylalanine.
Cysteine is synthesized from two other amino acids: methionine and serine
Serine serves as a precursor to glycine
Biosynthesis of Essential Amino Acids
Amino acid biosynthesis is regulated by allosteric mechanisms
The biosynthesis of amino acids is also regulated by changes in enzyme concentration
Glycine is a precursor of porphyrins
Certain genetic disorders lead to the accumulation of porphyrin derivatives
Bile pigments are formed as a result of the breakdown of heme groups
Purine nucleotides are synthesized via a complex pathway
The biosynthesis of purine nucleotides is regulated by feedback inhibition
Pyrimidine nucleotides are synthesized from aspartate and ribose phosphate
Regulation of Pyrimidine Nucleotide Biosynthesis
Ribonucleotides serve as precursors for deoxyribonucleotides
In humans, the degradation of purines leads to the formation of uric acid
Excessive production of uric acid causes gout
The ability to fix atmospheric nitrogen is limited to a relatively few organisms.
Nitrogen fixation is a complex enzymatic process
Photosynthesis
How the Photosynthesis Equation Was Derived
Photosynthetic organisms are exceptionally diverse
Hydrogen donors vary among different photosynthetic organisms
Plant photosynthesis takes place in chloroplasts
Light absorption excites molecules to a higher energy state
Chlorophylls are the primary light-absorbing pigments.
Thylakoids also contain accessory pigments
Thylakoid membranes contain two types of photochemical reaction systems
Light induces an electron flow in chloroplasts
The captured light energy generates an "uphill" flow of electrons.
The Z-scheme depicts photosynthetic electron transport as an energy diagram.
A number of carriers take part in photosynthetic electron transport
ADP phosphorylation is coupled with photosynthetic electron transport
Chloroplasts are also capable of cyclic electron flow and cyclic photophosphorylation.
Photosynthetic phosphorylation is similar to oxidative phosphorylation
General equation of plant photosynthesis
Photosynthetic hexose formation is coupled with the actual reduction of carbon dioxide
Carbon dioxide is fixed in the form of phosphoglycerate
Glucose is formed from CO2 in the Calvin cycle
Tropical plants utilize the C4 pathway, also known as the Hatch-Slack pathway.
The C4 pathway provides the necessary CO2 concentration
Photorespiration Limits the Productivity of C3 Plants
Photorespiration is a major challenge for agriculture in temperate zones
Halophilic bacteria use light energy for ATP synthesis
Photosynthetic organisms serve as models for the design of solar cells