Metabolic Regulation

Integration of cellular metabolism is controlled by insulin and the opposing actions of glucagon and epinephrine. When food is available in abundance, or when the body needs to make stored energy available, changes in the circulating levels of these hormones allow the body to respond accordingly. This discussion of metabolic regulation will be tailored to fit two scenarios, the fed and fasted states, and highlight how metabolite flux is modulated by the direct activating or inhibiting of enzymes, or by inducing or repressing their transcription in the nucleus.

• Introduction

Five major organs play dominant roles in fuel metabolism:

1. Liver
2. Adipose
3. Muscle
4. Pancreas
5. Brain

Each of these tissues possesses a unique repertoire of enzymes allowing them to differentially store, use, or generate specific fuels that the body needs. These tissues form a network with each other and do not function in isolation, and it is through this communication that one tissue is able to provide substrates to another. The nervous system mediates communication between tissues, along with circulating substrate availability and levels of plasma hormones.

Hormones induce the up- or down-regulation of the transcription of key enzymes in all pathways of intermediary metabolism.

Catabolism

Anabolism

Hormones

Insulin

Insulin is a polypeptide hormone produced by β-cells in the pancreatic islets of Langerhans. Its biosynthesis involves the production of two inactive precursors preproinsulin and proinsulin, which will be subsequently cleaved to form the active hormone upon a rise in blood glucose levels. Insulin causes glucose uptake in both myocytes and adipocytes and directs these cells to synthesize glycogen, protein, and triacylglycerols. These actions are mediated by insulin’s binding to the α-subunit of the insulin receptor, which produces a cascade of cell-signaling β-subunit of insulin receptor substrate (IRS) proteins.

Effect of insulin on glucose uptake and metabolism. Insulin binds to its receptor (1), which in turn starts many protein activation cascades (2). These include translocation of Glut-4 transporter to the plasma membrane and influx of glucose (3), glycogen synthesis (4), glycolysis (5) and fatty acid synthesis (6). It works at other sizes, but sometimes truncates the text on the far right.

Glucagon

Glucagon is a polypeptide hormone as well, produced by the α-cells of the pancreatic islets, in response to low blood glucose. Along with epinephrine (produced in the adrenal cortex), cortisol, and growth hormone, it acts to oppose insulin release, secretion, and uptake by peripheral tissues. These counter-regulatory hormones maintain blood glucose levels during the period of hypoglycemia, extreme exercise, or survival situations in which the “fight-or-flight” response is invoked.

Metabolic network showing the links between enzymes and metabolites that interact with the Arabidopsis TCA cycle KEGG classification M00009. Enzymes and metabolites are the nodes (red), interactions are the lines. In total, 43 enzymes and 40 metabolites are shown.

Glucagon increases the amount of available glucose by inducing glycogenolysis, gluconeogenesis, lipolysis, ketone body synthesis, and the uptake of amino acids by the liver. Free fatty acids released through lipolysis undergo β-oxidation, forming acetyl-CoA, which can enter the TCA cycle or be converted into ketone bodies.

Glucagon binds to high-affinity G-protein-coupled receptors that reside on the membranes of hepatocytes, resulting in the activation of the cyclic AMP (cAMP)-producing enzyme adenylyl cyclase. This second messenger acts to activate cAMP-dependent protein kinase A (PKA), which results in the phosphorylation-mediated activation or inhibition of the regulatory enzymes involved in carbohydrate and lipid metabolism. Note that the receptors that bind glucagon are different than the types that bind epinephrine or insulin and are not found in skeletal muscle.

Also employed to combat hypoglycemia is the hypothalamus, which has glucoreceptors to trigger the autonomic nervous system to secrete epinephrine, and the anterior pituitary to release adrenocorticotropic hormone (ACTH) and growth hormone (GH). ACTH increases cortisol synthesis and releases in the adrenal cortex. Catecholamines such as epinephrine and norepinephrine playing a supporting role in the fasted state as well, by causing similar cellular responses as those produced by glucagon.

Mechanisms of Metabolic Regulation

Four mechanisms dictate the flux of metabolites through their respective pathways:

1. Substrate availability
2. Allosteric enzyme regulation
3. Covalent enzyme modification
4. Regulation of enzyme synthesis, namely through the induction or repression of transcription.

Allosteric enzyme regulation occurs at rate-determining steps primarily. For example, following meal glycolysis in the liver is stimulated by the increase of fructose-2, 6-bisphosphate, which is an allosteric activator of phosphofructokinase-1 (PFK-1). In addition, the opposing pathway of gluconeogenesis is turned off by fructose-2, 6-bisphophate allosterically inhibiting fructose-1,6-bisphosphatase.

The addition or removal of phosphate groups from specific enzyme serine, threonine, or tyrosine residues allow for enzyme regulation through covalent modification. During the fed state, most of the enzymes regulated in this way will be dephosphorylated and active. Three notable exceptions to this generality are glycogen phosphorylase kinase, glycogen phosphorylase, and hormone-sensitive lipase, which are inactive when they are dephosphorylated. Note that these three enzymes play key roles in releasing stored energy, and so it makes sense to have them inactive during times when metabolites are in abundance.

Image: “A diagram showing at which stages in the DNA-mRNA-protein pathway expression can be controlled.” by ArneLH. License: CC BY-SA 3.0

Regulating enzyme synthesis by inducing or suppressing transcription allows the cell to increase or decrease the total number of key proteins of metabolic pathways, in contrast to allosteric or covalent modifications, which influence the efficiency of enzymes. This process is mediated by proteins that are typically activated or inhibited in the cytosol, usually by phosphorylation or dephosphorylation, and enter the nucleus to induce transcription of regulatory enzymes.

Example of Metabolic Regulation

For example, under fed conditions insulin induces both glycolysis and the pentose phosphate pathway. Protein phosphatase 2A (PP2A) is activated by xylulose-5-phosphate to dephosphorylate Carbohydrate response element-binding protein (ChREBP), which allows it to translocate into the nucleus and bind to Max-like protein (MLX) and induces the transcription of glycolytic enzymes (Hexokinase, PFK-1, PFK-2, Pyruvate kinase) through interaction with carbohydrate response element (ChORE). ChREBP also influences lipogenesis by enhancing the synthesis of Fatty acid synthase (FAS) and Stearoyl-CoA desaturase (SCD).

Image: “Stage 2 of the oxidative pentose phosphate pathway (OPPP): conversion of ribulose-5-phosphate into intermediates of glycolysis.” by C. Muessig. License: CC BY-SA 3.0

In addition, PP2A-mediated dephosphorylation of Sterol regulatory element-binding protein (SREBP1c) in response to insulin drives the cell to generate triacylglycerides from acetyl-CoA, by up-regulating the transcription of Acetyl-CoA carboxylase (ACC), FAS and SCD). SREBP1c is the master regulator of hepatic lipid metabolism.

Insulin also activates protein kinase B (PKB) to phosphorylate another protein, Forkhead box protein 01 (FOXO1). The result of this is that nuclear translocation is blocked, and no gluconeogenic enzymes (G₆Pase and PEPCK) are produced because phosphorylated FOXO1 is sent through the ubiquitin pathway to be destroyed.

In the fasted state, glucagon is released by pancreatic α-cells, which activates both PP2A and adenylyl cyclase. PP2A dephosphorylates (FOXO1), which promotes its translocation to the nucleus to induce the transcription of gluconeogenic enzymes G₆Pase and PEPCK. Adenylyl cyclase produces cAMP, which induces the phosphorylation and subsequent inactivation ChREBP by Protein kinase A (PKA). In this scenario, the enzymes of glycolysis and lipogenic pathways are attenuated, and the synthesis of enzymes involved in gluconeogenesis is up-regulated.

A sketch of activation effects of cAMP on Protein Kinase A

Covalent modifications occurring during the fasted state include the phosphorylation and activation of glycogen phosphorylase kinase, glycogen phosphorylase, and hormone-sensitive lipase, which allow the cell to mobilize stored glucose as well as lipids for breakdown and energy production when food is scarce or when the body needs to expend a lot of energy for a sustained period.

Other enzymes, such as pyruvate dehydrogenase (PDH), are inactive when phosphorylated. The resulting inhibition of PDH prevents muscle and other tissues from catabolizing glucose and gluconeogenesis precursors. Metabolism shifts toward fat utilization, while muscle protein breakdown to supply gluconeogenesis precursors is minimized, and available glucose is spared for use by the brain.

In summary, the body employs the brain, liver, adipose, pancreas, and skeletal muscle to govern intermediary metabolism. Minute-by-minute adjustments of blood glucose levels involve the combined actions of insulin, glucagon, epinephrine, and cortisol, which activate enzymes to covalently modify key regulatory enzymes. Allosteric modulations also occur in the short term, which presents a feedback measure to regulate enzyme activity.

Long term, the total amount of enzymes can be adjusted to reflect the state of nutrient availability, in either the fed or fasted states. Hormones signal covalent modifications that occur in the cytosol, which differentially induce or suppress proteins that translocate to the nucleus. Here, they up-regulate the transcription of key pathway enzymes.

This integration of metabolism allows the blood glucose level to be maintained through hormonally triggered cascades that counterbalance fluctuations, normally 60 to 90 mg/100 mL, or about 4.5mM due to dietary intake or vigorous exercise.

Gene Expression

Biochemistry Introduction and Overview

INTRODUCTION TO BIOCHEMISTRY

Medical biochemistry is an essential component of curriculum for all categories of health professionals. Contemporary Biochemistry plays a crucial role in the Medical field, be it metabolic pathways, storage diseases, mechanism action of varied biomolecules or inter and intra cellular communications. 

A lecture note on Medical biochemistry integrates and summarizes the essentials of the core subject. Topics are carefully selected to cover the essential areas of the subject for graduate level of Health sciences. The chapters are organized around the following major themes: 

1. Conformation of biomolecules, structure and their relationship to biological activity 

2. synthesis and degradation of major metabolites 

3. Production and storage of energy 

4. Biocatalysts and their application 

5. Intercellular communication by hormones 

6. Molecular events in gene expression and regulation 

Medical Definition of Biochemistry

Biochemistry: The chemistry of biology, the application of the tools and concepts of chemistry to living systems.

Biochemists study such things as the structures and physical properties of biological molecules, including proteins, carbohydrates, lipids, and nucleic acids; the mechanisms of enzyme action; the chemical regulation of metabolism; the chemistry of nutrition; the molecular basis of genetics (inheritance); the chemistry of vitamins; energy utilization in the cell; and the chemistry of the immune response.

Fields closely related to biochemistry include biophysics, cell biology, and molecular biology. Biophysics applies to biology the techniques of physics. Cell biology is concerned with the organization and functioning of the individual cell. Molecular biology, a term first used in 1950, It overlaps biochemistry and is principally concerned with the molecular level of organization.

The science of biochemistry has also been called physiological chemistry and biological chemistry.

History, Philosophical & Technological Improvement

Throughout history, organisms have changed their strategies to adapt to the changing circumstances on our planet. These changes have passed through inheritance over eons, and the result of this is the enormous diversity that has evolved. On the outside, a human being looks very different from a mushroom, but fundamentally they are both related to each other through their shared ancestry.

The human and the mushroom do not share every common property, but they do share a common chemical framework. This chemical framework is what evolves to allow different organisms to survive in a vast array of habitats, from inside animal intestines to thermal hot springs, from 5000 feet under the ocean surface to the coffee shop where you might be studying today.

Living known living organisms fall into one of the three large domains that define the “branches” of the so-called evolutionary tree that shows their course from a common progenitor. There are two groups of prokaryotes that can be distinguished for biochemistry reasons, the archaebacteria and eubacteria. Archaebacteria usually live in extreme environments, whereas eubacteria such as E. coli live in the same environments as eukaryotes do.

Biochemistry’s philosophy and technology have both “Co-Evolved” throughout their course history. Scientists have been asking biochemistry-related questions for hundreds of years, with no definitive start date.

The mid-20th century marked an explosion of technique development for the field of biochemistry, such as chromatography, X-ray diffraction, NMR, radioisotope labeling, and electron microscopy. These tools allowed scientists to analyze individual molecules and proteins and deduce metabolic pathways.

American biochemist Kary Mullis won the Nobel Prize in Chemistry (along with Canadian biochemist Michael Smith) for improving the technique of amplifying DNA through the polymerase chain reaction (PCR) first described by the 1968 Nobel laureate H. Gobind Khorana from India.

The philosophical views of biochemistry have also changed throughout history. The ideas leading to the hypothesis of Vitalism began in ancient Egypt, which states “living organisms are fundamentally different from non-living entities because they contain some non-physical element or are governed by different principles than are inanimate things.” This idea was widely accepted by many, including Swedish chemist and physician Jöns Jacob Berzelius, who in the early 19th century discovered several of the elements on the periodic table.

History

Modern chemistry: Antoine-Laurent Lavoisier (1743-1794), the father of modern chemistry, carried out fundamental studies on chemical oxidation and showed the similarity between chemical oxidation and the respiratory process.He began asking some of the first questions of biochemistry in his 1777 studies of how combustion is tied to respiration. Diastase (now called Amylase) was discovered by a French chemist named Anselme Payen in 1833, but most consider the birth of biochemistry as a field of study to have begun when a German chemist named Eduard Bucher described the process of fermentation in 1907.

Organic chemistry: In the 19th century, Justus von Liebig studied chemistry in Paris and carried the inspiration gained by contact with the former students and colleagues of Lavoisier back to Germany where he put organic chemistry on a firm footing.

Enzymes: Louis Pasteur proved that various yeasts and bacteria were responsible for "ferments," substances that caused fermentation and, in some cases, disease. He also demonstrated the usefulness of chemical methods in studying these tiny organisms and was the founder of what came to be called bacteriology. Later, in 1877 Pasteur's ferments were designated as enzymes.

Proteins: The chemical nature of enzymes remained obscure until 1926,when the first pure crystalline enzyme (urease) was isolated. This enzyme and all others proved to be proteins, which had already been recognized as high-molecular-weight chains of amino acids which we now know are the building blocks of protein.

Vitamins: The mystery of how minute amounts of dietary substances prevent diseases such as beriberi, scurvy, and pellagra came clear in 1935 when riboflavin (vitamin B2) was found to be an integral part of an enzyme.

ATP: In 1929 the substance adenosine triphosphate (ATP) was isolated from muscle. The production of ATP was found associated with respiratory (oxidative) processes in the cell and in 1940 ATP was recognized by F.A. Lipmann as the common form of energy exchange in cells.

Radioisotopes: The use of radioactive isotopes of chemical elements to trace the pathway of substances in the body was initiated in 1935 by R. Schoenheimer and D. Rittenberg, providing an important tool for investigating the chemical changes that occur in cells.


DNA: In 1869 a substance was isolated from the nuclei of pus cells and was called nucleic acid, which later proved to be deoxyribonucleic acid (DNA). It was not until 1944 that the significance of DNA as genetic material was revealed, when bacterial DNA was shown to change the genetic matter of other bacterial cells. Within a decade, the double helix structure of DNA was proposed by Watson and Crick, providing an understanding of how DNA functions as the genetic material.

DNA Animation Diagram

Ultimately Frederick Wöhler disproved this hypothesis by synthesizing urea, a constituent of urine, from ammonium and cyanate in the laboratory without the use of a cell. Philosophical views of biochemistry have co-evolved the development of technology, for example, Frederich Miescher’s isolation of DNA in the early 1900s.

The Avery-Macleod-McCarty Experiment demonstrated in 1944 that DNA is the substance that causes bacterial transformation, leading to the 1953 determination of DNA structure by Francis Watson and James Crick using X-Ray diffraction. This experimental evidence allowed for the development of the Central Dogma of Molecular Biology in the 1960s, which states that genetic information flows from DNA to RNA, and then to Protein.

Diversity and Spread of Life

Inside of any given living organism are cells that have a high degree of chemical complexity and microscopic organization. Their intricate internal structures have characteristic sequences of subunits, arranged to produce, for example, proteins with unique three-dimensional structures. Each of these unique proteins is highly specific for what types of molecules it will bind and interact with.

Living organisms also have systems for extracting energy from the environment, as well as transforming that energy into a usable form. They possess capabilities to replicate their genetic information and reproduce components of the cell, as well as the capacity to precisely regulate the interactions between those components.

This sophistication applies to the macroscopic structure, for example, the heart, but also applies to microscopic structures and individual chemical compounds throughout the organism. The dynamic environments of both the organism and the world outside of it come into contact with each other inevitably. This requires cells, tissues, organs, and organ systems to coordinate and compensate for changes in another. Possessing these abilities allows the whole organism to be greater than the sum of its individual parts.

On the microscopic scale, a biochemist sees a collection of molecules carrying out a program, whose result is both program reproduction as well as the self-perpetuation of that collection of individual molecules. In short, the biochemist sees life.

What Is Biochemistry?

Biochemistry is the study of the chemistry of living things. This includes organic molecules and their chemical reactions. Most people consider biochemistry to be synonymous with molecular biology.

What Types of Molecules Do Biochemists Study?

The principal types of biological molecules or biomolecules are:

• carbohydrates
• lipids
• proteins
• nucleic acids

Many of these molecules are complex molecules called polymers, which are made up of monomer sub units. Biochemical molecules are based on carbon.

What Is Biochemistry Used For?

• Biochemistry is used to learn about the biological processes which take place in cells and organisms.
• Biochemistry may be used to study the properties of biological molecules, for a variety of purposes. For example, a biochemist may study the characteristics of the keratin in hair so that shampoo may be developed that enhances curliness or softness.
• Biochemists find uses for biomolecules. For example, a biochemist may use a certain lipid as a food additive.
• Alternatively, a biochemist might find a substitute for a usual biomolecule. For example, biochemists help to develop artificial sweeteners.
• Biochemists can help cells to produce new products. Gene therapy is within the realm of biochemistry. The development of biological machinery falls within the realm of biochemistry.

What Does a Biochemist Do?

Many biochemists work in chemistry labs. Some biochemists may focus on modeling, which would lead them to work with computers. Some biochemists work in the field, studying a biochemical system in an organism. Biochemists typically are associated with other scientists and engineers. Some biochemists are associated with universities and they may teach in addition to conducting research. Usually, their research allows them to have a normal work schedule, based in one location, with a good salary and benefits.

What Disciplines Are Related to Biochemistry?

Biochemistry is closely related to other biological sciences that deal with molecules. There is considerable overlap between these disciplines:

1. Molecular Genetics
2. Pharmacology
3. Molecular Biology
4. Chemical Biology

The study of life in its chemical processes

Biochemistry is both life science and a chemical science - it explores the chemistry of living organisms and the molecular basis for the changes occurring in living cells. It uses the methods of chemistry,

"Biochemistry has become the foundation for understanding all biological processes. It has provided explanations for the causes of many diseases in humans, animals and plants."

physics, molecular biology, and immunology to study the structure and behaviour of the complex molecules found in biological material and the ways these molecules interact to form cells, tissues, and whole organisms.

Biochemists are interested, for example, in mechanisms of brain function, cellular multiplication and differentiation, communication within and between cells and organs, and the chemical bases of inheritance and disease. The biochemist seeks to determine how specific molecules such as proteins, nucleic acids, lipids, vitamins, and hormones function in such processes. Particular emphasis is placed on the regulation of chemical reactions in living cells.

An essential science

Biochemistry has become the foundation for understanding all biological processes. It has provided explanations for the causes of many diseases in humans, animals, and plants. It can frequently suggest ways by which such diseases may be treated or cured.

A practical science

Because biochemistry seeks to unravel the complex chemical reactions that occur in a wide variety of life forms, it provides the basis for practical advances in medicine, veterinary medicine, agriculture, and biotechnology. It underlies and includes such exciting new fields as molecular genetics and bioengineering.

The knowledge and methods developed by biochemists are applied to in all fields of medicine, in agriculture and in many chemical and health-related industries. Biochemistry is also unique in providing teaching and research in both protein structure/function and genetic engineering, the two basic components of the rapidly expanding field of biotechnology.

A varied science

As the broadest of the basic sciences, biochemistry includes many subspecialties such as neurochemistry, bioorganic chemistry, clinical biochemistry, physical biochemistry, molecular genetics, biochemical pharmacology, and immunochemistry. Recent advances in these areas have created links among technology, chemical engineering, and biochemistry.

FUNDAMENTALS OF BIOLOGY 

BIOCHEMISTRY

I. Basic Chemical Concepts

Atoms

1. Def.- the smallest unit of an element that can combine chemically with other elements
   Structure                                      
   1. Proton (+) charged
   2. Neutron (not charged)
   3. Electron (-) charged
      1. Electrons exist in distinct orbital clouds
      2. s, p, and d orbitals
      3. Orbitals combine to form energy levels: K, L, M, N, etc
   4. Protons and neutrons are the same mass and make up the nucleus
2. Identification
   1. Atomic number: number of protons
   2. Atomic mass number: number of protons + neutrons
   3. Atoms are organized into groups in the periodic table
3. Isotopes
   1. Two atoms with the same atomic number but different atomic mass numbers
   2. Differ only in the number of neutrons
   3. Some are radioactive (radioisotopes)

Compounds

1. Def: a combination of two or more elements which are joined chemically
2. Chemical bonding
   1. Ionic: when an atom will either give or take an electron from another atom
      1. Cation: positive ion
      2. Anion: negative ion
      3. Electrostatic forces hold the atoms together
   2. Covalent: when atoms share electrons
      1. Forms single or multiple bonds
      2. Sharing of electrons hold the atoms together
   3. Hydrogen bonds: weak links between the hydrogen (+) end of one polar molecule and the negative end of another polar molecule

Acids and Bases

1. Acid: a substance which releases a H+ ion
2. Base: a substance which releases an OH- ion
3. pH scale
   1. A method of determining how acidic or basic a solution is
   2. Negative logarithmic scale: 0 (acidic) to 14 (basic) (alkaline)
   3. pH 7.0 is neutral (water)
4. Buffers: a substance which limits the change of pH

Basic chemical reactions

1. Synthesis: two or more atoms or molecules are combined
2. Decomposition: molecules are broken down into simpler forms
3. Reduction
   1. The addition of electrons to a molecule
   2. Often accompanied by a gain of a hydrogen nucleus (proton)
4. Oxidation
   1. The removal of electrons from a molecule
   2. Often accompanied by a loss of a proton
   3. Oxidized atoms are more reactive than reduced atoms

II. Basic Biochemistry Concepts

A. Building Materials of Life

1. Inorganic compounds
2. Organic compounds
   1. All contain some form of carbon
   2. Biosynthesis: the manufacture of things by a living organism
3. Carbohydrates
   1. Structure
      1. Contain only C, H, and O
      2. Ratio of O:H is 1:2 (same as water H₂O)
   2. Reactions involving carbohydrates
      1. Dehydration synthesis: joining two molecules by removing water
      2. Hydrolysis: splitting two molecules by adding water
   3. Types
      1. Monosaccharides (simple sugars)
         1. 5-carbon: ribose
         2. 6-carbon: C₆H₁₂O₆ (Glucose, Galactose, Fructose)
      2. Disaccharides
         1. Two monosaccharides joined together (dehydration synthesis)
         2. Sucrose (table sugar): Glucose + Fructose
         3. Maltose (malt sugar): Glucose + Glucose
         4. Lactose (milk sugar): Glucose + Galactose
      3. Polysaccharides
         1. Starch: straight chain of glucose (food storage in plants)
         2. Glycogen: branched chain of glucose (food storage in animals)
         3. Cellulose: Zig-zag chain of glucose (non-digestible roughage)
4. Lipids
   1. Fats (triglycerides)
      1. 3 fatty acid molecules + 1 glycerol joined by dehydration synthesis
      2. Saturated: no double bonds between carbons
      3. Unsaturated: at least one double bond
   2. Phospholipids
      1. 2 fatty acids + 1 glycerol + 1 phosphate
      2. Hydrophobic end (fat): water fearing (non-polar)
      3. Hydrophilic end (phosphate): water loving (polar)
      4. Used extensively in cell membranes
   3. Sterols: multi-ringed compounds
      1. Cholesterol
         1. HDL: High density lipoprotein ("good" cholesterol)
         2. LDL: Low density lipoprotein ("bad" cholesterol)
      2. Hormones: i.e. prostaglandins, cortisone, etc
5. Proteins
   1. Structure: composed of 20 basic amino acids
   2. Protein synthesis
      1. Two amino acids are brought together and dehydration synthesis between the amino acids forms a peptide bond
      2. Protein = polypeptide chain
      3. The order of the amino acids is critical to the function of a protein
   3. Enzymes: large proteins which catalyze reactions
      1. Structure
         1. Active site: attachment site for substrates
         2. Substrate: molecule which reacts with the enzyme and is changed
         3. Coenzyme: non-protein which helps to complete the active site (vitamins)
      2. Enzyme action
         1. Enzyme & substrate bind at the active site
         2. Reaction proceeds (lytic- splitting apart, synthetic - putting together)
         3. Enzyme and product(s) separate
6. Nucleic acids
   1. Consist of long chains of repeating subunits (nucleotides)
   2. Nucleotide structure
      1. 5-carbon sugar (ribose)
      2. Phosphate group (PO₄)
      3. Organic nitrogen-containing base
   3. DNA: Deoxyribonucleic acid
      1. Used to store biological information
      2. DNA base pairs
         1. Guanine - Cytosine (G - C)
         2. Adenine - Thymine (A - T)
      3. Double-stranded helix shape formed by hydrogen bonds
   4. RNA: Ribonucleic acid
      1. Used as working blueprints for protein synthesis
      2. RNA base pairs
         1. Guanine - Cytosine (G - C)
         2. Adenine - Uracil (A - U)
      3. Single strand

III. Energy and its Changes

A. Kinetic energy: energy of motion

B. Potential energy: energy of position (stored energy)

C. Kinetic and potential energy are interconvertable

D. Energy in chemical reactions

1. Exothermic: reactions which release energy (heat)
2. Endothermic: reactions which require energy
3. Activation energy: energy needed to start a chemical reaction