Biochemistry Review Flashcards

Functional Groups and Biomolecules

• Find functional groups in any given molecule, focusing on atoms other than carbon (C) or hydrogen (H).
• Organic chemistry knowledge helps differentiate biomolecule classes.

Biomolecule Classes

• Proteins
  • Monomer units: Amino acids
  • Functions: Structure, enzymes, signaling
• Carbohydrates
  • Monomer units: Simple sugars (glucose)
  • Functions: Structure, energy storage (receptors)
• Lipids
  • Monomer units: Free fatty acids, acetyl group
  • Functions: Energy storage, cell membranes, signals
• Nucleic Acids
  • Monomer units: Nucleotides, bases (purines and pyrimidines)
  • Functions: Information storage, information transfer, regulation

Reactions of Lipids

• Unsaturated fatty acids (and oils) + H_2 --> saturated fatty acids
• Hydrogenation: Converts vegetable oils into solid fats (e.g., margarine).
  • Potential issue: Production of trans fats, which contribute to cardiovascular disease.
• Triglyceride hydrolysis (Saponification)

Lipid Classes/Properties/Function

• Recognize class structures of lipids.
• Draw a section of a membrane, including phospholipids, cholesterol, and proteins.

Carbohydrates

• Polyhydroxy aldehydes and ketones.
  • Contain an aldehyde or ketone.
  • Classified by the size of the carbon chain.
  • Names end with "-ose".
  • Example: Aldohexose (six-carbon aldehyde-containing sugar).
• Natural sugars range in size from 3 to 7 carbons long.
• Monosaccharides: Individual sugar.
• Disaccharides: Two sugars bonded together.
• Oligosaccharides: Several sugars bonded together (3-10).
• Polysaccharides: Many sugars linked together.
• Glycosidic Bond: The bond between two sugars.

Chirality in Sugars

• Sugars contain chiral carbons (carbon atoms bonded to four different groups).
  • Chiral carbons can adopt two mirror images, leading to stereoisomers.
• Enantiomers: Two mirror images of a chiral molecule.
• Diastereomers: Stereoisomers that are not mirror images (when two or more chiral carbons are present).
• Aldohexose family (six carbons and an aldehyde) has four chiral carbons, resulting in eight pairs of enantiomers.
• Biological importance: Only one enantiomer gives correct biological function.
  • In drugs, the other enantiomer can be toxic.
• Racemic Mixture: A mixture containing both enantiomers.
  • The amount of each enantiomer does not have to be equal.
• Most chemical and physical properties of enantiomers are identical, except for interaction with polarized light.
• Polarimetry: Experimental method using polarized light to distinguish between enantiomers.
• Enantiomers are distinguished by calling them right (dextro or d) or left (levo or l) based on their structure.

Fischer Projections

• Start with the aldehyde or ketone at the top of the structure, with carbons arranged vertically.
• The alcohol group on the chiral carbon farthest from the carbonyl group determines if the structure is d or l.
  • If the alcohol group is shown on the right, it is the d (dextro or right-handed) form.

Ring Structures (Haworth Projections)

• Sugars in solution (and solid forms) do not adopt the straight chain structure of the Fischer projection.
• The aldehyde or ketone reacts with an alcohol group to make a hemiacetal, resulting in a ring structure.
• The carbon of the aldehyde or ketone becomes a new chiral center, resulting in two possible structures.
• The new hemiacetal (or hemiketal) is drawn to the right, the last carbon is drawn above the plane of the newly formed ring.
• The new alcohol group of the hemiacetal can be:
  • Above the plane of the ring, cis to the last carbon: alpha isomer.
  • Below the plane of the ring and trans to the last carbon: beta isomer.
• Anomeric Carbon: The hemiacetal carbon.

Common Sugars

• Sucrose: Disaccharide of glucose and fructose (table sugar).
• Lactose: Disaccharide of galactose and glucose (milk sugar).
• Fructose: Ketohexose (fruit sugar or levulose).
• Glucose: Aldohexose (dextrose and blood sugar).

Carbohydrate Consumption

• Directly related to the formation of cavities.
  • More sugars in the diet increase the likelihood of cavities.

Polysaccharides

• Cellulose: Polymer of glucose, most common organic molecule in the world.
  • Makes up the woody part of plants, providing structure.
  • Not digested by animals, broken down only by a few bacteria. In humans, it is important as dietary fiber to aid gut motility.
• Chitin: Modified sugar polymer, second most common molecule in the world.
  • Makes up the exoskeleton of arachnids, lobsters, crabs, and scorpions.

Sugars as Energy Source

• Important energy source for almost all living organisms.
  • Plants store glucose as starch for later energy use.
  • Animals store glucose as glycogen for temporary energy storage.
• Starch and glycogen are similar, but glycogen has more branches and can be larger.
• Glycogen is found most in muscle and liver tissues.

Proteins

• Made by bonding amino acids together in peptide bonds (amide bonds).
• Each amino acid has an amine, carboxylic acid, and hydrogen bonded to the alpha carbon.
• The fourth group bonded to the alpha carbon (side chain or R group) defines the amino acid.
• Refer to the reactions of carboxylic acids for peptide bond formation and hydrolysis.

Protein Structure

• Primary Structure: The sequence of amino acids in the protein chain.
  • The first amino acid has an unreacted amine group (N-terminal amino acid).
  • The last amino acid has a free carboxylic acid group (C-terminal amino acid).
• Secondary Structure: Regular and repeating structural patterns (alpha helices and beta sheets) created by hydrogen bonding between backbone atoms.
• Tertiary Structure: Overall folding and bending of a single peptide chain.
• Quaternary Structure: Interactions between multiple peptide chains (a single protein chain does not have quaternary structure).
• Primary structure is achieved through forming a covalent bond.
• All other levels involve combinations of intermolecular forces and ionic and covalent links.
• Secondary structure is stabilized by hydrogen bonding of the backbone peptide bonds only.
• Tertiary and quaternary structures may also use disulfide links, salt bridges (between ions), and hydrophobic interactions for stability.

Protein Denaturation

• Interruption of the secondary through quaternary structures.
• Does not break amide bonds between the amino acids.
• Six agents that can cause denaturation: heat, change in pH, detergents, inorganic salts, mechanical agitation, and organic solvents.

Chirality and Protein Folding

• Chiral carbons are bonded to four different groups and have two mirror image structures.
• Only one of the two structures gives correct biological function.
• Amino acids are the L enantiomer.
• Only correct protein folding leads to proper biological function.

Prions

• Disease agents that are incorrectly folded proteins.
• Prions can cause other native proteins to misfold.
• Examples: Mad cow disease, scrapie (in sheep).
• Parkinson's and Alzheimer's diseases also seem to have misfolded proteins (but those proteins have not been called prions).

Enzymes

• Biological catalysts that speed up reactions without being used up.
• Can repeat the same reaction many times (10 to 1,000,000 reactions each second).
• Most enzymes are proteins, but some are RNA molecules (RNAzymes).
• Most of the enzyme structure supports positioning required functional groups in the active site.

Enzyme Active Site

• The place on the enzyme where the chemical reaction occurs.

Allosteric Sites

• Regions where small molecules bind and alter the enzyme's ability to perform its functions.
• Allosteric activators: Make the enzyme work faster.
• Allosteric inhibitors: Slow or stop the enzyme from reacting.

Cofactors

• Non-protein components necessary for enzyme activity.
• Examples: Metal ions, heme groups, organic molecules (coenzymes).
• Some vitamins contribute to coenzyme structures.

Enzyme Categories

• Oxidoreductases
• Transferases
• Hydrolases
• Isomerases
• Lyases
• Ligases
  • Understand generally what kind of reaction each category catalyzes.

Environmental Factors Controlling Enzyme Activity

• Heat: Initially speeds up a reaction, but excess heat will denature the enzyme.
• pH: Each enzyme has a narrow range of pH where it has optimal activity.
• Enzyme Concentration: The higher the enzyme concentration, the faster that reaction will happen.
• Cell Control:
  • Producing a precursor protein called a zymogen.
  • Only producing the enzyme when it is needed (genetic level control).
• Substrate Concentration:
  • Low substrate concentration controls the rate of the reaction.
  • High substrate concentration compared to enzyme: The enzyme is the limiting factor in the reaction rate.
  • The enzyme is said to be saturated.

Enzyme Specificity

• Enzymes that act on only one specific substrate and catalyze only one reaction are the most specific.
• Enzymes like the cytochromes P450 of the liver that oxidize many substances are some of the least specific.

Enzyme Control by Allosteric Modulators

• Enzymes are controlled by allosteric activators or inhibitors.
• Allosteric inhibitors are also known as uncompetitive inhibitors; they do not compete with substrate to bind the enzyme.

Feedback Control

• Some allosteric inhibitors are a product of a reaction at or near the end of a series of reactions—an enzyme pathway.
• Example: ATP inhibits the glycolysis pathway.
• Uncompetitive inhibitors will always slow reaction rates because the inhibitor can always bind the enzyme.

Competitive Inhibitors

• Bind the enzyme in the active site but do not undergo a reaction.
• Compete with the substrate if there is a free enzyme available.
• Can be swamped out by enough substrate, and the maximum enzyme rate is the same as when there is no inhibitor present.

Suicide Inhibitors

• Chemically react with and alter the enzyme, permanently disabling it.
• Many metal poisons act in this way.

Enzymes as Tissue Health Indicators

• Some enzymes are found in one or a few tissues or organs.
• When that organ is damaged, the cell contents are spilled into the blood.
• Enzymes uniquely found in one tissue can be measured in blood and used to monitor the health of that tissue.
• AST and ALT: Transferase enzymes found predominantly in the blood, used to monitor hepatitis.
• Amylase and lipase: Produced by the pancreas, indicate the health or disease/damage to that organ.

Generation of Energy and Metabolism

• Generation of energy is essentially how to produce ATP from our foods.
  • Starting with digestion of bulk food through burning food to carbon dioxide, creating water from oxygen.
  • Capturing and transferring electrons in the process (coenzyme function).
  • Making a proton (hydrogen ion) gradient that drives the final reaction of ADP + Pi --> ATP.
• ATP is considered the energy currency of the cell and drives many reactions and processes in the cell.

Metabolism

• The sum of all the processes that happen in a cell.
• Anabolism: The buildup of molecules, usually requires energy input.
• Catabolism: The breakdown of molecules, usually ends up creating energy.

Oxidation-Reduction Reactions

• Involve the transfer of electrons from one reactant to another.
• Most catabolism is driven by oxidation of carbon compounds with the eventual production of carbon dioxide and water.
• Carbon-based fuels are carbon in a reduced form.
  • Methane, CH_4, is the most reduced carbon compound.
• Carbon is oxidized when more bonds to oxygen are created or when hydrogen is removed.

Stages of Food Conversion to ATP

• Stage One: Digestion
  • Conversion of bulk food into small molecules that can be absorbed by the gut.
  • Involves mechanical processes (grinding food) and enzymatic processes.
  • Different foods are processed in the mouth, stomach, and small intestine.
• Stage Two: Production of Acetyl-CoA
  • Starts with small molecules and ends with the production of acetyl-CoA.
  • Each type of molecule (glucose, fatty acids, and amino acids) has its own processes in conversion to acetyl-CoA.
  • Acetyl-CoA is the common intermediate from all food sources.
  • Outputs: Reduced forms of coenzymes (NADH and FADH2).
  • Glucose also provides some ATP and CO_2.
• Stage Three: Citric Acid Cycle (Tricarboxylic Acid Cycle or Krebs Cycle)
  • Begins with input of acetyl-CoA.
  • More reduced coenzymes are produced in this cycle as the main means of capturing energy.
  • Some ATP (as GTP) is produced.
  • The majority of CO_2 is produced in this cycle.
• Stage Four: Electron Transport Chain (ETC) and Oxidative Phosphorylation
  • The electron transport chain starts with the oxidation of the reduced coenzymes.
  • The oxidized coenzymes can then be re-used to capture more electrons from the second and third stages.
  • Four separate enzyme complexes make up the ETC.
  • Two special coenzymes carry the electrons from one complex to the next: coenzyme Q and cytochrome C.
    • NADH enters the ETC at complex I.
    • FADH2 enters the ETC at complex II.
  • One function of the ETC is to create a hydrogen ion (proton) gradient between the inner and outer mitochondrial membranes.
  • Complex IV also converts oxygen to water using the electrons.
  • Without oxygen, the ETC grinds to a halt.

Anaerobic Fermentation

• The only process that can proceed in the absence of oxygen.
  • Glucose is converted to pyruvate via glycolysis, then pyruvate is converted to lactic acid in humans or ethanol in yeast or acetic acid by some bacteria.
  • These reactions reduce pyruvate and re-oxidize NADH to NAD+ to allow glycolysis to continue.
  • Only a few ATP are produced in anaerobic metabolism.

Coenzymes

• The role of the coenzymes (NAD+, FAD, and several others) is to capture and transfer reducing power (electrons) by cycling between oxidized and reduced forms.
• Ninety percent of ATP comes from these coenzymes.

Energy Production from Different Sources

• Fatty acids contain the most energy (most reduced carbon foods).
  • Lauric acid (200 g/mole) produces 95 ATP and is the slowest means of producing energy.
• Aerobic catabolism of glucose (180 g/mole) produces only 38 ATP.
• Anaerobic glycolysis produces ATP the quickest but provides only 2 ATP for each glucose molecule.

Diabetes

• The lack of transfer of blood glucose into cells.
  • Type I diabetes: Insulin is missing.
  • Type II diabetes: Insulin is ignored (insulin resistance).
• Cells cannot metabolize glucose and turn to other fuels (fatty acids and protein) for energy production.
• Beta-oxidation of fats produces acetyl-CoA faster than the citric acid cycle can process it.
• The excess bleeds over into the ketogenesis pathway, producing the three ketone bodies.

Ketone Bodies

• Acetone is expelled on the breath and gives a fruity odor to diabetics experiencing ketoacidosis.

Reactive Oxygen Species

• In normal circumstances, the electron transport chain will only partially reduce oxygen, producing reactive oxygen species—superoxide ion, hydrogen peroxide, and hydroxyl radical.
• Under some stress or disease conditions these species are increased.
• These species are very chemically reactive and can destroy the chemicals required for cell viability (membrane phospholipids, DNA, proteins).
• The cell has two enzymes, superoxide dismutase and catalase, and some vitamins (E, C and A) that are anti-oxidants to fight the reactive oxygen species.

Metabolic Intermediates

• Glucose (Glu-6-P), pyruvate, and acetyl-CoA are major intermediates in metabolism.
• Depending on cell conditions, each of these metabolites will flow into several pathways.

Metabolic Fates

• Glucose can be metabolized to pyruvate or temporarily stored as glycogen.
• Pyruvate can be metabolized aerobically to acetyl-CoA, anaerobically to lactic acid or ethanol, or converted to glucose via gluconeogenesis.
• Acetyl-CoA can enter the Krebs cycle, lipogenesis, or ketogenesis (there is a common start to steroids and ketone bodies).

Amino Acids

• The precursors for building proteins are the 20 amino acids.
• Some are essential (cannot be produced by our cells and must be in our diets).
• When used to generate energy, each amino acid follows its own pathway to that common intermediate, acetyl-CoA.

Ketogenic vs Glycogenic Amino Acids

• Some amino acids are converted directly into acetyl-CoA or acetoacetyl-CoA; these are called ketogenic amino acids.
• Amino acids that are converted into pyruvate or a Krebs cycle intermediate can feed into gluconeogenesis and are called glycogenic amino acids.
• Some larger amino acids have carbons that feed into both processes.
• The common issue with amino acids for generating energy is the removal and disposal of the nitrogen, the amine group.
• Ammonia is converted in the liver to urea which may be safely excreted in the urine.

Lipoproteins

• Triglycerides and cholesterol are hydrophobic and must be transported in the blood.
• Packages called lipoproteins are used to transport these important lipids in the blood stream.
• Four major lipoproteins classified by their density.

Lipoprotein Classes

• Chylomicrons: Carry dietary lipids (mostly triglycerides but also some cholesterol) from the gut to the rest of the body.
• Very Low-Density Lipoproteins (VLDL): Carry triglycerides from the liver to the rest of the body.
• Low-Density Lipoprotein (LDL): Delivers cholesterol from the liver to the rest of the body.
  • LDL is the main lipoprotein that increases atherosclerotic plaques that lead to heart disease and strokes—it is often called “bad cholesterol.”
• High-Density Lipoproteins (HDL): Collect excess cholesterol from cells and return it to the liver.
  • HDL is “good cholesterol” and high levels of HDL are considered cardio protective—they reduce the risk of heart attack and stroke.

Cholesterol and Heart Health

• LDL increases atherosclerotic plaque development, increases the risk of heart disease and stroke, and is "bad cholesterol."
• HDL decreases plaques, reduces the risk of heart disease, and is "good cholesterol."

Biochemistry Metabolic Pathways

Nucleic Acids

Central Dogma of Molecular Biology

• DNA --> RNA --> Protein
• RNA viruses (like COVID-19 virus)

Building Blocks of Nucleic Acids

• Nucleotides
• Bases: adenine, guanine, thymine (DNA only), cytosine, and uracil (RNA only)
• Identify the phosphate, sugar, and base building blocks on a drawing.

DNA vs RNA Structures

• DNA contains deoxyribose (no hydroxyl group on the 2' carbon).
• RNA contains uracil; DNA contains thymine.
• RNA is single-stranded (but may fold into 3-D structures); DNA is double-stranded.
• DNA is millions of base pairs long; RNA is usually no larger than 10,000 bases.

Types of RNA and Their Roles in Protein Synthesis

• hnRNA (heteronuclear RNA): Initial transcript of the DNA, includes introns (intervening sequences) and exons (expressed sequences). Introns are removed by the spliceosome to create mRNA.
• mRNA (messenger RNA): Carries the information, or message, from the nucleus to the ribosome. Contains the triplet code read by the tRNA.
• tRNA (transfer RNA): Transfers the correct amino acid to the growing peptide strand. Reads the message from mRNA.
• rRNA (ribosomal RNA): Part of the protein synthesis molecular complex. Participates in the enzymatic reactions creating peptide bonds.

DNA Replication

• Helicase binds at multiple origins of replication to create replication forks on each chromosome.
• Helicase opens the double-stranded DNA, exposing single strands of DNA.
• DNA polymerase binds at the replication fork and copies each strand of DNA in the 5' to 3' direction.
• The base added to the growing strand is complimentary to the template strand (G opposite C and A opposite T).
• The leading strand is copied continuously.
• The lagging strand must be copied in sections, called Okazaki fragments (because DNA polymerase can only copy in the 5' to 3' direction).
• DNA ligase comes after DNA polymerase and joins the Okazaki fragments into a single strand.
• The new copies each contain a new strand and an old strand—a semiconservative copy process.

DNA and RNA in Heredity and Genetic Expression

• DNA is found as chromosomes.
• Each cell has 2 copies of each chromosome (except X and Y for men).
• One copy of each chromosome comes from the father, the other copy comes from the mother.
• DNA is the information carrier and has a role in heredity (children inherit DNA from both parents).
• The control regions of genetic expression are found in the DNA.
• New research suggests long-noncoding RNA (lnRNA) plays a role in organizing the chromatin in the nucleus and thus helps with controlling which genes are expressed.
• Gene expression depends on the production of mRNA and the translation of the mRNA into protein.
• The number of mRNA copies made and the number of times each mRNA is translated into protein regulates gene expression.

Types of Mutations

• Types of mutations including silent mutations.
• These are to be distinguished from polymorphisms—different naturally occurring DNA sequences in a given gene between individuals.