Biochemistry: Foundational Concepts

Biochemistry Definition

• It's the study of life at the molecular level.
• Chemistry principles are applied to explain biology.
• Underlies common sets of reactions and principles in living organisms.
• It's essentially the study of the molecular logic of life.

Biochemistry's Unity

• Living organisms are remarkably uniform at the molecular level.
• A common set of building blocks are used by all, creating nucleic acids, proteins, polysaccharides, and lipids.
• Essential biochemical processes have a common core in all organisms.

Life's Foundations

• Life is understood from four different perspectives.
• These are: Chemical, Energy, Genetic and Evolutionary.

What Makes Us Up? (Chemical)

• Living things are made from simple, common ingredients.
• Carbon, oxygen, hydrogen, and nitrogen make up 98% of most organisms.
• Water accounts for much of the oxygen and hydrogen in living things.
• All known life forms are carbon based.

Chemical requirements from Our Environment

• Chemical elements within the biosphere are readily available:
  • Plants facilitate the intake of carbon from atmospheric carbon dioxide through photosynthesis.
  • Oxygen readily available in the air.
  • Hydrogen from water.
• Air contains abundant nitrogen but it’s unavailable due to it's inert form as N2.
• Nitrogen within the biosphere comes from plants and ultimately from soil.
• Nitrogen in soil limits plant growth and reduces available food.
• The amount of naturally occurring nitrogen enables growth of food that can feed about 4 billion people

The Carbon Foundation

• Carbon is extremely versatile because of the number and variety of chemical bonds.
• Silicon is the "next-best" candidate as a chemical foundation for life.
  • It can form four covalent bonds.
  • Silicon is highly abundant in Earth.
• However carbon is the superior foundation compared to silicon:
  • Carbon bonds are stronger than silicon bonds, thus more stable biomolecules.
  • Combustion of carbon produces significant amounts of energy.
  • Carbon combustion products (carbon dioxide) are soluble and active in the biosphere.

Functional Groups

• Different functional groups have unique size, shape, charge, reactivity, and hydrogen-bonding capacity.
• Functional groups determine the structure, function, and properties of biomolecules.

Structure Dictates Function

• The structure determines the function for all biomolecules. A critical course goal is understanding the structure-function relationships of biomolecules.
• A molecules structure causes it to "do what they do"
• Understanding biomolecule structure enables prediction of molecular function, understand complex biology including disease, and develop treatment strategies.
• Conformation = flexible spatial arrangement of atoms within a molecule that can be achieved via breaking covalent bonds.
• Configuration = fixed spatial arraignment of atoms within a molecule, no breaking of bonds.
  • Configuration is conferred by double bonds or chiral centers.

Double Bonds

• Geometric (cis-trans) isomers have the same chemical formula, but differ in the configuration of groups with respect to a non-rotating double bond.
• Cis: "on this side" groups on the same side of the double bond.
• Trans: "across" groups on opposite sides of the double bond.
• Geometric (cis-trans) have very different biological properties.

Chiral Carbons

• A chiral carbon has four different substituents, and their isomers may arrange in different ways which result in configuration.
• Stereoisomers’ chemical properties tend to be identical, but their biological properties are distinct.

Stereospecific Biochemistry

• Biochemistry is stereospecific in these ways:
  • Construction: Biomolecules tend to be constructed from only one stereoisomer.
  • Interactions: Interactions between biomolecules tend to be stereospecific.

Complex Molecules from Simple Precursors

• Biomolecules are generally polymers of simple building blocks.
• The structure and function of biomolecules is more complex than their precursor molecules.
• Building biological molecules with polymers has these advantages:
  • Simplicity: Use of simple conserved reactions for synthesis and degradation.
  • Recycling: biomolecules can be digested into reusable building blocks.
  • Diversity: Capable of generating incredibly complex molecules.

Classes of Biomolecules

• There are four major classes of biomolecules
• Proteins
• Carbohydrates
• Nucleic Acids
• Lipids

Proteins

• Linear polymers of amino acids.
• There are 20 different amino acids.
  • Sequence determines structure.
  • Structure determine function.
• Amino acids link together to form linear chains, then fold with biological activity.

Carbohydrates

• Monosaccharides link together to form linear or branched polymers.
• Serve many important biological roles including structural, energy storage, and cellular recognition.

Nucleic Acids

• Linear polymers of nucleotide building blocks (DNA & RNA).
• Involved in all aspects of genetic information storage and utilization.

Lipids

• Lipids are aggregates, not defined polymers, of building blocks.
• Lipids participate in energy storage, membrane formation, and signaling.

Prokaryotes vs Eukaryotes

• There are two basic classes of living organisms, prokaryotes and eukaryotes:
• Prokaryotes
  • Small (1µm diameter), simple, single cell organisms (ex: bacteria).
  • Adapt to environmental changes by quick growth, they are contained within the nucleoid.
• Eukaryotes
  • Larg (~100 µm diameter), complex cells.
  • Multi-cellular organisms such as yeast, plants, fungi, vertebrates
  • Organelles (nucleus, mitochondria, golgi, endoplasmic reticulum, to support specialized functions.
  • Differentiated by cell type

Boundaries Blurred

• The human body contains around 30 trillion eukaryote cells.
• The human body also contains around 100 trillion prokayotic cells.
  • These play a critical roll in health by digesting food, support of gut flora, impacting mental health (depression, anxiety), obesity, and intelligence.
• Influencing the microbiome can be achieved through diet, pre- and probiotics, and fecal transplants.

In vitro vs In vivo

• Within the cell biomolecules undergo complex, organized interactions.
• Studying these cellular interactions drives the challenge of biochemistry
• Studying isolated molecules is simpler than live models however it may not produce biologically significant data
  • In vitro studies the behaviour of molecules outside the context of the cell and organism.
  • In vivo studies occur within the complexity of the cell or organism.
• Experiments are often successful in vitro can fail in vivo.

Energy

• The energy to be alive must be obtained from the environment.
• It would cost $4.5 million/day to commercially purchase the ATP that a body requires.
• Energy is an important course theme, specifically in quantitative and chemical terms.
• Energetics of biomolecular conformational changes and understanding how free energy contributes to reaction rates and equilibrium (enzymes).
• Cellular energy conversion can be considered in the context of the laws of thermodynamics.

First Law of Thermodynamics

• In any physical or chemical change, the total amount of energy in the universe remains constant, forms of energy may change.
• Cells are highly effective transducers of energy by converting the energy of metabolized nutrients, or the energy of the sun, into work, heat, or the generation of complex biomolecules.

Second Law of Thermodynamics

• Nature drives towards disorder (entropy).
• Living systems require a high degree of organization.

Gibbs Free Energy

• Willard Gibbs developed the theory of energy changes during chemical reactions.
• He defined free energy (G) of any closed system in terms of Enthalpy (H), Entropy (S), and Temperature.
  • Enthalpy (H): reflects the number and kinds of bonds present.
  • Entropy (S): The degree of randomness.
  • Temperature: In degrees Kelvin.

Gibbs Definitions

• The definition of free energy is : G = H - TS
• Thus, the free energy change is: ΔG = ΔH - TΔS

The Meaning of Free Energy

• AG > 0
  • Non-spontaneous process, needs input of free energy to proceed. endergonic
• AG < 0
  • Spontaneous process, releases free energy which can be used to do work; proceeds until equilibrium is reached. exergonic
• AG = 0
  • System is at equilibrium, there is no change in free energy in the system.

Reactions in Biology

• Cells can drive thermodynamically unfavorable reactions by coupling energy requiring (endergonic) to energy releasing (exergonic) reactions.
• If the sum of the free energy changes is negative, then the overall process is exergonic (spontaneous).

ATP

• Extracted energy is converted to adenosine triphosphate (ATP).
• ATP is a common carrier of energy in cells, linking reactions in catabolism and anabolism.
• Catabolism = breaking down molecules.
• Anabolism = building up molecules.

Genetics

• The perpetuation of life requires:
  • That genetic information must be stored in a stable form.
  • Must be expressed accurately in the form of gene products.
  • Must be reproduced with minimal errors.
• DNA provides instructions for cell components along with a template to produce identical DNA to give to progeny when cells divide.

Replication

• DNA's basic unit is two complimentary strands.
• Each strand is a linear polymerase of four different types of building blocks.
• It is strands’ linear sequence that encodes information.

Protein Structure

• Genes' nucleotide sequence dictates amino acid sequence which dictates protein structure and resultant biological activity.

Evolution

• Random changes in genotype (genetic information) can change phenotype (observable characteristics).
• If change can provide a survival advantage it will be selected for over time, if it disadvantages the organism its disadvantage will be selected against.

Explore the core principles of biochemistry, from the unity of life's chemical processes to the central role of carbon. Understand how chemistry and biology intertwine in living organisms. This quiz probes the shared biomolecular basis of all life forms.