Biochemistry

ChemistrySurvival.com ©2006 All Right Reserved

Biochemistry Core Concept Master Cheat Sheet

Biochemistry, 1 of 6 01: The Science of Chemistry

• Matter & Energy: Matter (anything made from atoms) Pure Substance Mixtures Elements Compounds Homogeneous Heterogeneous • (Hydrogen) (H2O) (Tap water) (sand & water) Energy Kinetic Energy (KE) Potential Energy (PE) (related to speed of particles) (stored in chemical bonds) • Physical and Chemical Changes: Physical Changes • Do not create a new substance. • All changes in state (between solids, liquids and gases) are

physical changes. Breaking, cutting, dissolving, drying, melting, freezing, etc. Chemical Changes • Do produce new substances. • Some signs of a chemical change are:

o production of a gas (bubbles) o heat change (getting hot or cold) o light o change in color o Formation of a precipitate (forming an insoluble

substance from two soluble substances. • However, some of these signs could be present in physical

changes as well. Rusting, burning, reacting with water, reacting with acid, etc.

02: Chemistry Review • Tetrahedral geometry: Geometry of four atoms or groups

around a carbon atom. Look at the diagram of methane CH4

• Homolytic cleavage: Radicals are formed.

BrBr 2 Br

• Heterolytic cleavage: Ions are formed.

ClH H Cl+

Heterolytic cleavage: • London dispersion forces: Forces between nonpolar

molecules. • Dipole-dipole forces: Forces between polar molecules. • Hydrogen bonding: Between compounds with –OH, -NH,

or HF.

CH

H

H

H CH

H

H

Cl CH

H

H

O H

London disperson dipole-dipole hydrogen bonding

03: Introduction to Biochemistry • Biochemistry: The chemistry of biology, the application of

the tools and concepts of chemistry to living systems. • Biomolecules: The molecules those are present in the

living beings. • Hydrophobic. Preferring not to be in contact with water • Hydrophilic: Polar or charged molecules that dissolve

readily in water. • Coenzyme: An organic molecule that associates with

enzymes and affects their activity. • Hexose. A sugar with a six-carbon backbone. • Nucleotide. An organic molecule containing a purine or

pyrimidine base, a five-carbon sugar (ribose or deoxyribose), and one or more phosphate groups. A phosphoester of a nucleoside.

• Fatty acid: A linear carbon chain with a carboxylic acid group at one end

• Biomolecules Vitamins & • Minerals • • Carbohydrates Proteins Nucleic acids Lipids • (Glucose, (Albumin, (DNA, (Cholesterol, • starch etc) Hemoglobin) RNA) Fatty acids) Biochemical Reactions: • Hydrolysis: The cleavage of a molecule by the addition of

water. Hydrophilic. Preferring to be in contact with water. • Deamination: The enzymatic removal of an amine group, as

in the deamination of an amino acid to an alpha keto acid. • Oxidation: The loss of electrons from a compound. • Transamination: Enzymatic transfer of an amino group from α-amino acid to α- keto acid.

• Polypeptide. A linear polymer of amino acids held together by peptide linkages. The polypeptide has a directional sense, with an amino- and a carboxy-terminal end.

04: Water • Ion product of water: (Kw) the product of the

concentrations of H+ and OH- in pure water. Kw = 1 x 10-14 at 25’ C.

• Buffer: A system capable of resisting changes in pH, consisting of a conjugate acid-base pair in which the ratio of proton acceptor and proton donor is near unity.

• Entropy: (∆S) the extent of randomness or disorder of a system.

• Enthalpy (∆H): The heat content of a system. • Condensation: A process wherein two molecules join

together by a specific bond resulting in the loss of a water molecule.

• Hydrolysis: Chemical process in which a molecule is cleaved into two parts by the addition of a molecule of water.

• Dissociation constant: An equilibrium constant Kd for the dissociation of a complex of two or more Biomolecules into its components.

• Dilution factor: The ratio of the initial and final solution volumes (v1/v2). The following equation is very useful in calculating final concentration of a solution after dilution.

• M1V1 =M2V2 • Where M1 and V1 refer to the initial concentration and

volume of the solution and M2 and V2 refers to the final concentration and volume of the solution.

• pH: Defined as the negative logarithm of hydrogen ion concentration. It is a measure of acidity of a solution.

• The Hendorson-Hasselbach equation is used to calculate the

pH of blood in clinics.



Biochemistry, 2 of 6 05: Thermodynamics for Biochemistry

• Heat: Flow of energy from a hotter object to cooler object. • Endothermic reaction: Energy is absorbed into the

system from the surroundings. • Exothermic reaction: Energy is released from the system

into the surroundings. • First law of thermodynamics: Energy can not be created

nor destroyed in a chemical or physical process. • Thermal equilibrium: Two objects at different

termperatures will come to the same temperature when placed together.

• Second law of thermodynamics: Every spontaneous process has an increase in the entropy of the universe.

• Energy Units: Joule (J) or Calorie (Cal) • 4.18 J = 1.00 Cal. • Temperature: Higher the temperature, faster the molecules

move. • Equilibrium: When the rate of the forward and the reverse

of a reversible process are equal. • Dynamic equilibrium: The number of reactants and

products do not change but the reaction continues to occur in both directions.

• Equilibrium constant (k): The value found when equilibrium concentrations are plugged into the equilibrium constant expression.

• Reversible reaction: Reaction that can proceed in both directions.

• Free energy change: • ∆G = ∆H – T∆S • Where: ∆G is the free energy change. • ∆H is the change in enthalpy. • ∆S is the change in entropy. • T is the temperature in Kelvin. •

06: Amino Acids, Peptides & Proteins • Peptide bond forms between two amino acids and it

connects them. In this way, many amino acids can be connected to yield a big structure called a polypeptide or a protein.

• Coding of amino acids is an easy way to remember the names of amino acids.

• Covalent bond: A chemical bond that involves sharing of electron pairs.

• Polypeptide: A long chain of amino acids linked by peptide bonds.

• Conformation: The spatial arrangement of substituent groups that is free to assume different positions in space without breaking any bonds, because of the freedom of single bond to rotate.

• Amino acids in solution at neutral pH exist predominantly as dipolar ions (also called zwitterions).

• The hydrophobic amino acids tend to repel the aqueous environment and, therefore, reside predominantly in the interior of proteins. This class of amino acids does not ionize nor participate in the formation of H-bonds.

• The hydrophilic amino acids tend to interact with the aqueous environment, are often involved in the formation of H-bonds and are predominantly found on the exterior surfaces proteins or in the reactive centers of enzymes.

• Proteins: • Almost all biochemical reactions are carried out by proteins. • Structures such as muscle depend on protein–protein

interactions • Proteins are not extended arrays of amino acids but often

have a compact three-dimensional array.

07: All About Proteins • Beta-sheet (ß-sheet): A sheet like structure formed by the

interaction between two or more extended polypeptide chains.

• Disulfide Bridge: Covalent linkage formed between two cysteine- SH groups either in the same polypeptide chain or in different polypeptide chains.

• Globular protein: A folded protein that adopts an approximately globular shape. May also be called soluble proteins.

• Isoelectric point or pH: The pH at which a protein has no net charge.

• X-ray crystallography is an experimental technique that exploits the fact that X-rays are diffracted by crystals.

• Structural protein. A protein that serves a structural function.

• 3D structure of Hemoglobin • • • • • • The picture shows the 4 monomeric subunits of Hemoglobin; They are colored differently for clarity the individual subunits are polypeptide chains This picture represents the quaternary structure of the protein. There are two alpha and two beta subunits. The 3D structure is important for its function. •

08: Chemistry of Carbohydrates

• • Mutarotation: The Alpha and Beta froms of D-Glucose

interconvert in aqueous solution.This process is known as mutarotation.

• Formation of glycosides: Glycosides are formed when the hemi acetal or hemi ketal hydroxyl group of a carbohydrate reacts with a hydroxyl group of another carbohydrate or non-carbohydrate. Ex:Lactose

• Important Mucopolysaccharides:

Important Mucopolysaccharides • They are also known as glycosaminoglycans. • Chondroitin 4-sulfate • Heparin • Dermatan sulfate • Keratan sulfate

Carbohydrates

Disaccharides Monosaccharides Oligosaccharides

Ketoses

Aldoses

Non-Reducing

Reducing Example: Trisaccharides

Heteropolysaccharides

Homopolysaccharides

H

Broadly classified into four categories

Polysaccharides



Biochemistry, 3 of 6 09: Lipids and Membranes

• Fat: an ester of fatty acids with glycerol as the alcohol. • Fatty acid: Aliphatic, carboxylic acid with general

structural formula R-COOH, R being a hydrocarbon chain. • Essential fatty acids: Are those which can not be

synthesized by the body and have to be supplied in the diet.

• Lecithin: Phospholipid with choline as the nitrogeneous base. Contains two fatty acids, usually fatty acid attached to 2nd carbon atom is PUFA.

• Cholesterol: Is a derived lipid with steroid nucleus and one hydroxyl group. It is a 27 carbon compound.

• Lipid Bilayer: It is the basic structure of the cell membrane, their polar head groups orient towards water and non polar tails towards non aqueous solution.

10: Nucleic Acids • Nucleic Acids • • • DNA RNA • A,B,Z are various forms • of DNA • m-RNA r-RNA t-

RNA • B form: The most common form of duplex DNA,

containing a right-handed helix and about 10 (10.5 exactly) base pairs per turn of the helix axis.

• Watson-Crick base pairs: The type of hydrogen-bonded base pairs found in DNA, or comparable base pairs found in RNA. The base pairs are A-T, G-C, and A-U.

• Double helix: A structure in which two helically-twisted polynucleotide strands are held together by hydrogen bonding and base stacking.

• Nucleotide: The fundamental unit (monomer) of the nucleic acid polymer.

• Phosphodiester: A molecule containing two alcohols esterified to a single molecule of phosphate. For example, the backbone of nucleic acids is connected by 5'-3' phosphodiester linkages between the adjacent individual nucleotide residues.

• In eukaryotes, DNA is contained in the cell nucleus • A DNA molecule consists of two long polynucleotide chains

composed of four types of nucleotide subunits, ATP, TTP, GTP, CTP.

• RNA like DNA is a long unbranched macromolecule consisting of nucleotides joined by 3'- 5' phosphodiester bonds.

11: Enzyme – The Basic Concept • Enzyme: An enzyme is a protein that catalyzes or speeds

up a chemical reaction. • Catalyst: A catalyst is a substance that accelerates the

rate (speed) of a chemical reaction without itself being transformed or consumed by the reaction.

• Substrate: A substrate is a molecule which is acted upon by an enzyme.

• Active site: The active site is the location on the surface of the enzyme where the catalysis of chemical reaction takes place.

• Activation energy (Ea): The amount of energy required to convert all reacting substances from ground state to transition state. Enzymes work by reducing the Ea of the reaction.

• Prosthetic group: A metal ion or an organic compound that is covalently bound to an enzyme required for its activity.

• Holoenzyme: A complete catalytically active enzyme with its cofactor.

• Cofactors: Cofactor

Inorganic ions organic molecule

Activators coenzyme prosthetic group Hypothesis: Enzyme Substrate Complex • Lock and Key Hypothesis • Induced fit Hypothesis

12: Enzyme Kinetics and Catalysis

• Michaelis-Menten kinetics: A kinetic pattern in which the

initial rate of an enzyme-catalysed reaction exhibits a hyperbolic dependence on substrate concentration. • Factors affecting enzyme activity:

1. Concentration of the substrate and Michaelis – Menten Kinetics

2. Temperature 3. pH 4. Product concentration Three types of Reversible Inhibition: Competitive inhibition Non-competitive inhibition Uncompetitive inhibition

Lipids

Membrane lipidsStorage lipids

Fats and oils Waxes Glycerophospho

Cholesterol

Sphingolipids

Simple Mixed

Micelle, Liposome,Bilayer

Broadly Classfied as

Are of 3 types Based on type of alcohol

As per fatty acid content

Enzymes - Biocatalysts

Acid-Base Catalysis

Diseases

pH, temperature, Concentration of Substrate, Inhibitors Cofactors

Alter

Catalysis takes place by several processes

Rate of Biochemical Reactions

Influencing factors

Covalent Catalysis

Metal ion Catalysis

Transition state Stabilization

Function defects cause

Lysozymes

Ribozymes



Biochemistry, 4 of 6 13: Metabolism & Energetics

• • Reducing equivalent: A general or neutral term for an

electron or an electron equivalent in the form of a hydrogen atom or a hydride ion.

• Redox potential (Eo): The oxidation – reduction potential is a quantitative measure of the tendency of a redox pair to lose or gain electrons. The redox pairs are assigned specific standard redox potential (Eo volts) at pH 7.0 and 25o Celsius. • ATP: Universal currency of free energy in biological

systems. ATP is an energy-rich molecule because its triphosphate unit contains two phospho anhydride bonds. Made up of an Adenine, a ribose and a triphosphate unit.

• Oxidation: Loss of electrons. • Reduction: Gain of electrons.

14: Glycolysis • Glycolysis: Glycolysis is the sequence of reactions that

converts glucose into pyruvate with the concomitant production of a relatively small amount of ATP.

• Glycolytic Pathway: • Preparatory phase

Glucose ATP hexokinase

ADP

Glucose-6-phosphate phosphohexoseisomerase

Fructose-6-phosphate

ATP Phosphofructokinase-1 ADP

Fructose-1,6-bisphosphate aldolase

Glyceraldehydes-3 Dihydroxyacetone phosphate phosphate

Triosephosphate Isomerase

The citric acid cycle – under aerobic condition and oxidized to CO2 and H20 • Entry of StoragePolysaccharide: Glycogen

Glycogen phosphorylase Debranching enzyme Glycogen glucose-1-phosphate phosphoglucomutase Glucose-1-phosphate Glucose-6-phosphate

15: Citric Acid Cycle • Cellular respiration: The term respiration is used to refer

to the process in which cellular energy is generated through the oxidation of nutrient molecules, with O2 as the ultimate electron acceptor.

• Anaplerotic reaction: An enzyme catalyzed reaction that

can replenish the supply of intermediates in the citric acid cycle.

• Amphibolic pathway: A metabolic pathway used in both catabolism and anabolism.

16: Carbohydrate Metabolism II Pentose Phosphate Pathway: Metabolic pathway

involving metabolism of numerous sugars, mostly with five carbons. The pathway is a source of ribose for nucleotides and NADPH for biosynthesis. Secondary pathway for glucose metabolism also termed as phosphogluconate pathway.

Glyoxylate Cycle:

• Precursors of gluconeogenesis: Alanine from transamination in liver as pyruvate. Lactate from active muscles after conversion to pyruvate in liver. Fatty acids after oxidation as propionyl coA that is subsequently converted to oxaloacetate. Glycerol from triacylglycerol hydrolysis as as DHAP.

Pyruvate 3C

Acetyl-CoA 2C

Oxaloacetate 4C

Citrate 6C

Isocitrate 6C

Ketogluterate 5C

Succinyl CoA 4C

Succinate 4C

Fumerate 4C

Malate 4C

Fatty acids and glycerol

Acetyl CoA

Fats Proteins Polysaccharides

Glucose and other sugars Amino acids

CoA

Citric acid cycle

2 CO2

e- O2

ADP

ATP

Oxidative phosphorylation

STAGE I

STAGE II

STAGE III



Biochemistry, 5 of 6 17: ETC

• Electron transport chain: A set of proteins and other electron-carrying molecules in the inner membrane of the mitochondrion.

• Oxidative phosphorylation: Oxidative phosphorylation is a process where the energy of biological oxidation is ultimately converted to the chemical energy of ATP.

• Electron Carriers: • Integral membrane proteins embedded in the inner

mitochondrial membrane • Arranged into complex- I, II, II and IV • Accepts or donates electrons from preceeding carrier to

the following in sequence • Constitutes – electron carrying groups – ubquinone (UQ),

cytochromes (cyt) and iron-sulfur proteins(Fe-S) • Electron carrying sources – Pyridine nucleotides (NAD or

NADP) or flavin nucleotides (FMN or FAD). • Flow of electrons through carriers:

Complex I NADH + H+ FMN Fe2+S CoQ

NAD+ FMNH2 Fe3+S CoQH2 Complex II Succinate FAD Fe2+S CoQ Fumarate FADH2 Fe3+S CoQH2 Complex III CoQH2 cyt b ox Fe2+S cyt c1ox cyt c red CoQ cyt b red Fe3+S cyt c1 red cyt c ox Complex IV cyt c red cyt a ox cyt a3 red O2 cyt c ox cyt a red cyt a3 ox 2 H2O

• P/O Ratio: • Determines efficiency of oxidative phosphorylation • P/O - measure of the molecules of ATP made per pair of

electrons carried through the electron transport. • Electrons from NADH have a P/O ratio - 3/1. • Electrons FAD have a P/O ratio - 2/1.

18: Photosynthesis • Basic Concept of Photosynthesis: • Solar energy Chloroplast Light reaction O2 Dark reaction ATP and NADH CO2 O2 Carbohydrates Heterotrophs CO2 H2O Photophosphorylation: The enzymatic formation of ATP from ADP coupled to the light-dependent transfer of electrons in photosynthetic cells. Photosystem: In photosynthetic cells, a functional set of light-absorbing pigments and its reaction center. Light Absorbing pigments: • Chlorophylls: Green pigments with polycyclic, planar

structure. Chlorophyll a and chlorophyll b are prominent in higher plants located in thylakoid membranes of chloroplasts.

• Accessory pigments: The secondary light absorbing pigments. Ex: Carotenoids and phycobilins

• Carotenoids: yellow, red or purple pigments. • Eg: β –carotene – red-orange isoprenoid and Xanthophyll –

yellow • Phycobilins: Phycocyanin and phycoerythrin.

19: Lipid Metabolism

Normal Serum Levels: Total Serum Cholesterol 150 – 280 mg/dL LDL Cholesterol < 190 mg/dL HDL Cholesterol Males: 45 +/- 12 mg/dL

Females: 55 +/- 12 mg/dL Triacylglycerol (TAG) < 165 mg/dL • β - Oxidation: Successive oxidation at the β- carbon atom

of fatty acyl co A, producing acetyl co A. • Fatty acid synthase: It is a multienzyme complex involved

in the synthesis of fatty acid. • Atherosclerosis: It is a complex disease characterized by

thickening or hardening of arteries due to the accumulation of cholesterol.

20: Amino Acid Metabolism

• Urea cycle is depicted above.

• Transamination: Enzymatic transfer of an amino group from an alpha-amino acid to an alpha-keto acid.

• Transdeamination: The combined action of the amino transferases and glutamate dehydrogenase is referred to as transdeamination.

• Aminotransferases: Enzymes that catalyze the transfer of amino groups from alpha-amino to alpha-keto acids, also called transaminases.

Argininosuccinate

Ornithine

Arginine

Citrulline

H2O

H2N – C –NH2

O

Aspartate R – NH2

Fumarate

Carbomoyl phosphate

R – C – NH2 O

CO2 + NH4+

Mitochondrial Matrix

Cytosol

Urea

Site: Liver Subcellular site: Mitochondria, Cytosol

Urea Cycle

Chylomicrons

VLDL

TAGs

Liver

TAG

FFA

CHO CO2

FFA

Ketone Bodies (KB)

Adipose Tissue

Intestinal Dietary TAG

Enter intestinal mucosal cell and with other lipids form

Transport

Lipoprotein lipase act on TAGs to release FFA

FFA FFA

Lipoprotein lipase act on TAGs to release FFA

TAG

Extrahepatic Tissue

TAG

KB

CO2

CHO

Cholesterol, its esters

TAG – Triacylglycerol CHO – Carbohydrates FFA – Free fatty acid VLDL – Very low density lipoprotein



Biochemistry, 6 of 6 21: Nucleotide Metabolism

• Nucleotide Synthesis:

• • Lesch-Nyhan Syndrome: Disorder caused due to genetic

lack of hypoxanthine-guanine phosphoriboryl-transferase activity seen exclusively in male children, who are mentally retarded and badly co-coordinated.

• Gout: Disease wherein increased uric acid is seen which gets deposited in synovial fluid of joints resulting in inflammation.

• Uric acid: product of catabolism of purines in human beings.

• Allopurinol: Inhibitor of xanthine oxidase in purine catabolism.

• Xanthine Oxidase: Enzyme catalyzing two reactions in purine nucleotide catabolism, hypoxanthine to xanthine, then to uric acid.

22: DNA Structure and Replication • DNA replication: • DNA • (deoxyribonucleic acid) • • • Relax of DNA supercoil by topoisomerase • • • Unwind of DNA double strains by helicase • • • Synthesis of RNA primer by primase • • • Synthesis of DNA by DNA polymerase • • • Ligation of DNA fragment by ligase • Significance of DNA replication: • DNA replication provides a heritage base of life: • DNA replication is semi-conservative. • DNA polymerases are template-directed enzymes. • DNA polymerase has function of readproof. • Watson-Crick Rules: Describe the model of DNA and

paring rules of DNA bases: adenine (A) specifically binds to thymine (T) and cytosine (C) specifically binds to guanine (G).

• Semi-Conservative DNA Replication: Each of two strains is used as a template for synthesis of the newly developed strain. The newly synthesized strain is complement of the template.

•

23: RNA Structure and Synthesis • RNA synthesis: • DNA as Template • (deoxyribonucleic acid) • Transcription factors binding to promotor • • RNA polymerase unwind a DNA next to a gene • Elongation at the direction from 5’ to 3’ • Termination with/without ρ fator • Processing/Splicing (removing intron and add poly-A) • • Messenger RNA (mRNA): Carries the genetic information

copied from DNA in the form of a series of three-base code “words,” each of which specifies a particular amino acid

•

24: Protein Biosynthesis • Map of Protein Biosynthesis:

• • Wobble in Protein Translation:

1. Codons that encode the same a.a. often differ only by their third base.

2. The binding of the third base is less stringent than the other two.

3. Because of this wobble one tRNA can pair with multiple mRNA codons.

tRNAmRNA

Transcription

rRNA

DNA

Ribosome

tRNA

AA

rRNA

mRNA

tRNA

AA

protein

Translation

AA

snRNAtRNA

mRNA

rRNA

Broadly classified into five categories

snoRNA

RNA

Nitrogenous Base

Nucleotide

Nucleoside

Adenine, Guanine

Purines/ Pyrimidines

Deoxyribonucleotide Ribonucleotide

On addition of Phosphate

If Pentose is Ribose

If Pentose is Deoxyribose

On polymerization On polymerization

Nucleic acid RNA Nucleic acid

On addition of Pentose

Thymine, Cytosine, Uracil

Documents

Biochemistry