Principles of Biochemistry Volume 3 - A. Lehninger 1985



Selected Aspects of Human Biochemistry

Digestion, Nutrient Transport, and Intermediary Metabolism

Food undergoes enzymatic digestion to prepare it for subsequent absorption

Digestion, Nutrient Transport, and Metabolic Interrelationships

The liver processes and distributes nutrients

The liver possesses five distinct pathways of sugar metabolism

There are also five metabolic pathways for amino acids

Digestion, nutrient transport, and metabolic interrelationships

There are five pathways of lipid transformation

Each organ possesses specialized metabolic functions

Skeletal muscles use ATP to perform mechanical work as needed

Digestion, Nutrient Transport, and Metabolic Interrelationships

The cardiac muscle must work continuously and rhythmically

Digestion, nutrient transport, and metabolic interrelationships

The brain utilizes energy to transmit impulses

Digestion, nutrient transport, and metabolic interconnection

Adipose tissue is characterized by an active metabolism

Digestion, nutrient transport, and metabolic interrelationships

Kidneys use ATP to perform osmotic work

Blood has a very complex composition

Digestion, Nutrient Transport, and Intermediary Metabolism

Blood carries large volumes of oxygen

Digestion, nutrient transport, and metabolic interconnection

Hemoglobin as an oxygen carrier

Digestion, Nutrient Transport, and Metabolic Interrelationships

Erythrocytes also transport CO2

Diagnosis and treatment of diabetes mellitus rely on biochemical assay data

In diabetes, the level of ketone bodies increases

In diabetes, urea excretion increases

Severe diabetes is accompanied by acidosis

Chapter Summary

Hormones

Hormones function within a complexly overlapping hierarchical system

Some General Properties of Hormones

Hypothalamic and pituitary hormones are peptides

The adrenal medulla secretes amine-class hormones: adrenaline and noradrenaline

Epinephrine stimulates the formation of cyclic adenosine monophosphate

cAMP stimulates protein kinase activity

The stimulation of glycogen breakdown in the presence of epinephrine occurs via an amplification cascade

Epinephrine also inhibits glycogen synthesis

Phosphodiesterase inactivates cyclic adenosine monophosphate

The pancreas secretes a number of hormones that regulate metabolic processes

Insulin: A Hypoglycemic Hormone

Insulin secretion is regulated primarily by blood glucose concentrations

The secondary messenger of insulin action remains unknown

Insulin affects many metabolic processes

Glucagon is a hyperglycemic hormone of the pancreas

Somatostatin inhibits the secretion of insulin and glucagon

Somatotropin also influences the action of insulin

Adrenal cortex hormones are steroids

Thyroid hormones regulate the metabolic rate

Sex hormones are steroids

The mechanism of action of estrogens on target cells is gradually becoming clearer

There are many other hormones present in the organism

Prostaglandins and thromboxanes influence the action of a number of hormones

Chapter Summary

Human Nutrition

A balanced diet must contain five essential components

The body derives energy through the oxidation of organic macronutrients

Selected aspects of human biochemistry

Human nutrition

Ethanol also serves as a source of energy

Some aspects of human biochemistry

Obesity results from the consumption of excessively calorie-dense foods

Selected Aspects of Human Biochemistry

Human Nutrition

Proteins are essential as sources of amino acids

Certain plant proteins in food can be mutually complementary

Starvation and Kwashiorkor: Global Public Health Challenges

Deficiency of certain vitamins can be life-threatening

Thiamine deficiency remains a nutritional concern

Dietary intake of nicotinamide and tryptophan is interrelated

Many food products contain little ascorbic acid

Riboflavin deficiency is a phenomenon as common as ascorbic acid deficiency

Folic acid deficiency is the most common occurrence

Deficiencies of pyridoxine, biotin, and pantothenic acid in humans are extremely rare

Dietary vitamin B12 deficiency is extremely rare

Some Aspects of Human Biochemistry

Vitamin A deficiency leads to numerous consequences

Selected Aspects of Human Biochemistry

Vitamin D deficiency leads to rickets and osteomalacia

Vitamin E or K deficiency in humans is extremely rare.

Human nutrition must include a wide range of chemical elements

Some aspects of human biochemistry

Human nutrition

Calcium and phosphorus are essential for the development of bones and teeth

Selected Aspects of Human Biochemistry

Human Nutrition

Mild magnesium deficiency is a relatively common phenomenon

The sodium and potassium content in food is of great importance for the prevention and treatment of hypertension

Iron and copper are essential for the synthesis of heme proteins

Selected aspects of human biochemistry

Human nutrition

Goiter is a result of iodine deficiency

Selected Aspects of Human Biochemistry

Human Nutrition

Dental caries is an important nutrition-related problem

Zinc and Certain Other Trace Elements as Essential Dietary Components

A balanced diet must be multicomponent

Certain aspects of human biochemistry

Human nutrition

Special food labels serve the interests of consumers

Molecular Mechanisms of Genetic Information Transfer

DNA: Structure of Chromosomes and Genes

DNA and RNA perform different functions

DNA and RNA nucleotide units contain specific bases and pentoses

Molecular mechanisms of genetic information transmission

DNA: structure of chromosomes and genes

Consecutive nucleotides are linked by phosphodiester bonds

DNA stores genetic information

Molecular Mechanisms of Genetic Information Transmission

DNA: Structure of Chromosomes and Genes

DNA from different species has a distinct nucleotide composition

Molecular Mechanisms of Genetic Information Transfer

Watson and Crick postulated the double helix model of DNA

Molecular mechanisms of genetic information transfer

DNA: structure of chromosomes and genes

The nucleotide sequence of DNA serves as a template

Molecular Mechanisms of Genetic Information Transmission

DNA: Structure of Chromosomes and Genes

DNA double helices can undergo denaturation, i.e., unwind

Molecular Mechanisms of Genetic Information Transfer

DNA strands from two different species can form DNA-DNA hybrids

Certain physical properties of double-stranded DNA reflect the ratio of G=C to A=T base pairs in its composition

Native DNA molecules are extremely fragile

Viral DNA molecules are relatively small in size

Chromosomes of prokaryotic cells are single, very long DNA molecules

Molecular mechanisms of genetic information transfer

DNA: structure of chromosomes and genes

Circular DNA is supercoiled

Molecular Mechanisms of Genetic Information Transmission

DNA: Structure of Chromosomes and Genes

Some bacteria contain DNA in the form of plasmids

Molecular mechanisms of genetic information transfer

DNA: Structure of chromosomes and genes

Eukaryotic cells contain significantly more DNA than prokaryotes

Molecular Mechanisms of Genetic Information Transmission

DNA: Structure of Chromosomes and Genes

Eukaryotic chromosomes consist of chromatin fibers

Histones are small basic proteins

DNA-histone complexes form bead-like nucleosomes

Eukaryotic cells also contain cytoplasmic DNA

Molecular Mechanisms of Genetic Information Transfer

Genes are regions of DNA that encode polypeptide chains and RNA

A large number of genes are concentrated in a single chromosome

What are the sizes of genes?

Molecular mechanisms of genetic information transfer

DNA: structure of chromosomes and genes

Bacterial DNA is protected by restriction-modification systems

DNA: Structure of chromosomes and genes

Eukaryotic DNAs contain highly repetitive base sequences

Molecular Mechanisms of Genetic Information Transfer

DNA: Structure of Chromosomes and Genes

Some eukaryotic genes are present in multiple copies

Molecular Mechanisms of Genetic Information Transmission

Eukaryotic DNA contains a large number of palindromes

Molecular mechanisms of genetic information transfer

DNA: Structure of chromosomes and genes

Many eukaryotic genes contain intervening untranslated sequences (introns)

Molecular Mechanisms of Genetic Information Transfer

DNA: Structure of Chromosomes and Genes

The nucleotide sequences of several DNAs have already been deciphered

Chapter Summary

DNA Replication and Transcription

DNA replicates in a semi-conservative manner

Molecular mechanisms of genetic information transfer

DNA replication and transcription

Circular DNA replicates bidirectionally

Eukaryotic DNAs have multiple origins of replication

Molecular Mechanisms of Genetic Information Transfer

DNA Replication and Transcription

Sometimes DNA is replicated via a “rolling circle” mechanism

Bacterial extracts contain DNA polymerase

DNA polymerase action requires a pre-existing DNA template

Molecular mechanisms of genetic information transfer

DNA replication and transcription

DNA replication requires numerous enzymes and protein factors

Molecular Mechanisms of Genetic Information Transfer

DNA Replication and Transcription

E. coli cells contain three DNA polymerases

Simultaneous replication of both DNA strands poses challenges

Discovery of Okazaki Fragments

An RNA primer is required for the synthesis of Okazaki fragments

Okazaki fragments are joined together by DNA ligase

Replication requires the physical separation of the strands of the parental double-stranded DNA

DNA polymerases can detect and correct errors

Molecular Mechanisms of Genetic Information Transmission

Replication in eukaryotic cells is particularly complex

Molecular mechanisms of genetic information transfer

DNA replication and transcription

Genes are transcribed to form RNA

Molecular Mechanisms of Genetic Information Transfer

DNA Replication and Transcription

Messenger RNAs encode polypeptide chains

Molecular Mechanisms of Genetic Information Transmission

Messenger RNA is synthesized by means of DNA-dependent RNA polymerase

Molecular mechanisms of genetic information transfer

DNA replication and transcription

Eukaryotic cell nuclei contain three RNA polymerases

DNA-dependent RNA polymerase can be selectively inhibited

RNA transcripts undergo further processing

Molecular Mechanisms of Genetic Information Transmission

DNA Replication and Transcription

Heterogeneous nuclear RNAs serve as precursors to eukaryotic messenger RNAs

Molecular mechanisms of genetic information transfer

DNA replication and transcription

Introns must be removed from mRNA precursors

Small nuclear RNAs help remove introns from RNA

Molecular Mechanisms of Genetic Information Transfer

DNA Replication and Transcription

Transcription can be observed

In RNA-containing viruses, DNA is transcribed using reverse transcriptase

Molecular mechanisms of genetic information transfer

DNA replication and transcription

Some viral RNAs are replicated using an RNA-dependent RNA polymerase

Molecular Mechanisms of Genetic Information Transfer

DNA Replication and Transcription

Polynucleotide phosphorylase enables the synthesis of RNA-like polymers with a non-specific nucleotide sequence

Chapter Summary

Protein Synthesis and Its Regulation

Early discoveries laid the foundation for research into protein biosynthesis

Protein synthesis proceeds in five main stages

tRNA is required for amino acid activation

Aminoacyl-tRNA synthetases attach the corresponding amino acid to tRNA

tRNA acts as an adaptor

Polypeptide chain synthesis begins at the N-terminus

Molecular mechanisms of genetic information transfer

Protein synthesis and its regulation

The initiating amino acid in prokaryotes is N-formylmethionine, and in eukaryotes, methionine

Molecular Mechanisms of Genetic Information Transfer

Protein Synthesis and Its Regulation

Ribosomes are molecular machinery designed for the synthesis of polypeptide chains

Molecular mechanisms of genetic information transfer

Protein synthesis and its regulation

Eukaryotic cytoplasmic ribosomes are larger in size and have a more complex structure

Molecular Mechanisms of Genetic Information Transmission

Protein Synthesis and Its Regulation

Polypeptide chain initiation occurs in several stages

Molecular Mechanisms of Genetic Information Transfer

Polypeptide chain elongation is a repeating process

A special signal is required for the termination of polypeptide synthesis

Energy is required to ensure the accuracy of protein synthesis

Polyribosomes enable rapid translation of a single template

Molecular mechanisms of genetic information transfer

Protein synthesis and its regulation

Polypeptide chains undergo folding and processing

Molecular Mechanisms of Genetic Information Transfer

Protein Synthesis and Its Regulation

Newly synthesized proteins are directed to their cellular destinations

Molecular mechanisms of genetic information transfer

Protein synthesis and its regulation

Protein synthesis is inhibited by various antibiotics

Molecular mechanisms of genetic information transmission

The genetic code has been deciphered

The genetic code possesses a number of interesting features

Molecular Mechanisms of Genetic Information Transfer

Protein Synthesis and Its Regulation

The "wobble" hypothesis allows a number of tRNAs to recognize multiple codons

Molecular mechanisms of genetic information transfer

Protein synthesis and its regulation

Viral DNAs sometimes contain genes within other genes or overlapping genes

Protein synthesis is regulated

Molecular Mechanisms of Genetic Information Transfer

Protein Synthesis and Its Regulation

Bacteria contain constitutive and inducible enzymes

Enzyme repression also occurs in prokaryotes

Molecular mechanisms of genetic information transfer

Protein synthesis and its regulation

The operon hypothesis

Molecular Mechanisms of Genetic Information Transfer

Protein Synthesis and Its Regulation

Repressor molecules were isolated

Molecular Mechanisms of Genetic Information Transmission

Operons also contain a promoter region

Molecular Mechanisms of Genetic Information Transfer

Chapter Summary

More About Genes: Repair, Mutation, Recombination, and Cloning

Damage is constantly occurring in DNA

Regions damaged by ultraviolet radiation can be excised and repaired

More on Genes: Repair, Mutation, Recombination, and Cloning

Spontaneous deamination of cytosine to uracil can be repaired

More About Genes: Repair, Mutation, Recombination, and Cloning

Damage caused by environmental chemical agents can also be repaired

More on Genes: Repair, Mutation, Recombination, and Cloning

A change in a single base pair causes a point mutation

Nucleotide insertions and deletions cause frameshift mutations

More About Genes: Repair, Mutation, Recombination, and Cloning

Mutations are random, rare events in the lives of individuals

More on Genes: Repair, Mutation, Recombination, and Cloning

Many mutagens cause cancer

Genes frequently undergo recombination

More About Genes: Repair, Mutation, Recombination, and Cloning

Chromosome regions frequently undergo rearrangement

More on Genes: Repair, Mutation, Recombination, and Cloning

Antibody Diversity Results from Translocation and Recombination

Molecular Mechanisms of Genetic Information Transmission

More About Genes: Repair, Mutation, Recombination, and Cloning

Genes from different organisms can be artificially combined

Molecular Mechanisms of Genetic Information Transfer

More on Genes: Repair, Mutation, Recombination, and Cloning

Plasmids and phage lambda serve as vectors for introducing foreign genes into bacteria

Gene Isolation and cDNA Synthesis

Construction of a Gene-Bearing Vector

Integration of "loaded" plasmids into the E. coli chromosome

cDNA cloning can be used to search for corresponding natural genes

Expression of cloned genes is enhanced using a promoter

Recombinant DNAs and gene cloning have opened up new directions in genetic research

The study of recombinant DNA is of great practical importance

Interferon gene cloning has been successfully achieved

Chapter Summary

Unit designations, prefixes, constants, and conversion factors

Atomic mass of elements

Logarithms

Answers

Glossary of Terms