B3 Carbohydrates

B.3.1 Describe the structural features of monosaccharides
Monosaccharides 
** contain a carbonyl group (C=O) and at least two -OH groups, and have the empirical formula CH2O
- are the simplest carbohydrates (quickest energy source)
- 2 main types of carbs: simple sugars (monosaccharides) and complex (polysaccharides)
- most common: triose (C3), pentose (C5), hextose (C6)
- large no. -OH groups, hence readily soluble in water


B.3.2 Draw the straight-chain and ring structural formulas of glucose and fructose
Must be aware of the structural difference between α and β isomers.

 

B.3.3 Describe the condensation of monosaccharides to form disaccharides and polysaccharides
Monosaccharides - simple sugars
Disaccharides - two simple sugars linked together
e.g. lactose, maltose and sucrose
Polysaccharides - polymers of sugars
e.g. starch (α-glucose), glycogen (α-glucose) and cellulose (β-glucose)

Disaccharides
- condensation produces disaccharide AND water, -OH group from each sugar molecule reacts together and creates a glycosidic link (essentially an ether bond between the two)
- all soluble
- hydrolysed into 2 monosaccharides, through acid hydrolysis/ enzyme-catalysed reaction
- combining different monos. = different disaccharides

(all have the formula C12H22O11)

Polysaccharides
- held together by glycosidic bonds
- all insoluble, hence ideal for energy storage
- 3 most common glucose based: starch, glycogen, cellulose

Starch
- rich sources: rich, potatoes, flour
- mixture of amylose and amylopectin

 

Glycogen
- α-glucose polymer
- 'animal starch' because it is the main storage carb in animals
- found in liver and muscles
- similar to amylopectin, but more 1-6 branches

Cellulose
- β-glucose polymer
- structural material for plant cell walls
- linear polymer with 1-4 linkage (β-glycosidic links), hence positions sugars at different angles to α-glycosidic links in amylose and amylopectin.
- cellulose chain forms uncoiled linear structure with alternate glucose monomers 'upside down' (to polymerise, one of the glucose molecules in turned upside down to form the glycosidic linkage. The hydroxyl groups form h-bonds with the hydroxyl of another cellulose molecules)
- forms cables called microfibrils, parallel chains that give it its rigid structure (one of the main supports in plant cells)

B.3.4 List the major functions of carbohydrates in the human body
Providing energy (glucose)
- carbs broken into carbon dioxide and water during respiration
- exothermic, hence releases lots of energy

Storing energy (glycogen)
- polysaccharides (starch) are good stores of carbs
- usually within the liver and released when needed

Building blocks
- precursors for other important biological molecules


B.3.5 Compare the structural properties of starch and cellulose, and explain why humans can digest starch but not cellulose.
Both are polymers of glucose units. Starch has 2 forms: amylose (straight chain polymer, α-1,4 linkage), and amylopectin (branched structure with both α-1,4 and α-1,6 linkages)
Cellulose has a β-1,4 linkage, which can be hydrolysed by cellulase (although absent in most animals/mammals)

Polysaccharides
- insoluble, therefore cannot be transported in blood
- needs to be broken into its monos. units
- through hydrolysis, glycosidic links broken and soluble monosaccharides produced - controlled by enzymes that are very specific in their actions.

Enzymes
- produced in the body to break down polys. into glucose that's then absorbed into the body.
- enzyme for β-glycosidic link (in cellulose, hemicellulose etc.) not produced in the body, cellulase needed, maybe secreted in small amounts by bacteria (microflora) living in the gut, but generally not digested and passes through.


B.3.6 State what is meant by the term dietary fibre.
Dietary fibre - mainly plant material that is not hydrolysed by enzymes secreted by the human digestive tract but may be digested by microflora in the gut. E.g. cellulose, hemicellulose, lignin and pectin.


B.3.7 Describe the importance of a diet high in dietary fibre.
Good sources high in dietary fibre includes foods derived from plants with little/no processing
May be helpful in the prevention of conditions of:
- irritable bowel syndrome
- constipation
- obesity
- Crohn's disease
- hemorrhoids
- diabetes mellitus

Cellulose fibrils abrades the wall of the digestive tract and stimulates lining to provide mucus - smoothing the passage of undigesteds through the gut.

B2 Proteins

B.2.1 Draw the general formula of 2-amino acids.

B.2.2 Describe the characteristic properties of 2-amino acids
Properties should include isoelectric point, formation of a zwitterion and buffer action.

Amino acids
Crystalline compounds with high melting points, usually above 200 degrees celsius
Greater solubility in water than non-polar solvents

Zwitterions - dipolar ions (positive and negative charge on same group of atoms)

Aminos are amphoteric, in Zwitterions it is the conjugate acid and base that's responsible for this property. In aqueous solution they can accept and donate H+ depending on the pH of the medium. As they can accept/donate it can resist small changes in pH - they can act as buffers, which is important to maintain body cell pH.
E.g. Enzymes are sensitive to pH change and can be destroyed easily by significant flucuations
pH determines net change
Positive (+) at low pH
Negative (-) at high pH

At the isoelectric point it is neutral at intermediate pH. There is no net change, amino acids will not move in an electric field, minimal repulsion, therefore least soluble.

B.2.3 Describe the condensation reaction of 2-amino acids to form polypeptides.
Reactions involving up to three amino acids will be assessed.
Different sequences = different peptides formed. (2 2-amino acids = dipeptide)
Uses condensation reaction - peptide and water are formed.

B.2.4 Describe and explain the primary, secondary (α-helix and β-pleated sheets), tertiary and quaternary structure of proteins. 
Include all bonds and interactions (both intramolecular and intermolecular) responsible for
the protein structure.

Primary structure = the amino acid sequence
Secondary structure = depends on the hydrogen bonding
Tertiary structure = depends on the interaction between R groups
Quaternary structure = association between different polypeptides

Primary structure (the sequence of amino acids)
- held together by peptide bonds
- dictates the entire structure and function of the protein
- extremely crucial, a change in one amino acid can change the entire functioning of the protein e.g. disease sickle-cell anemia. The disease occurs because of a single change in the chain of 146 amino acids, and the hemoglobin is unable to carry oxygen efficiently

Secondary structure (the folding of the polypeptide chain based on the side chains)
- the folding can differ in different proteins, or even in different sections of the same protein.
- the folding occurs as a result of hydrogen bonding between C=O and N-H groups of different peptide bonds
- 2 structures: α - helix & β - pleated sheet
- are fibrous proteins
- physically tough and insoluble in water

α - helix
- a tight coil, with 3.6 amino acids per turn, because of h-bonds formed between 2 peptide bonds 4 amino acids apart.
- flexible, elastic, because the intra-chain h-bonds break and reform easily as the molecule is stretched
- e.g Keratins, found in hair, skin + nails.

β - pleated sheet

- 'side by side' polypeptide
- extended form, not tightly wound
- pleated sheets cross-linked by inter-chain h-bonds
- flexible, inelastic
- e.g. fibers by spiders + silkworms, beaks

Tertiary structure (interactions between R groups)
Conformation
- relates to the most stable arrangement of the protein
- depends on the interaction of the R groups (the intra-molecular forces)
- important in globular proteins (this includes all enzymes and protein hormones)

Globular proteins 
- water soluble, because nearly all polar R groups are on the surface of the molecule they can interact with water, while the non-polar ones are mostly inside, out of contact with water.
The R-group interactions that stabilizes the conformation are the:
Hydrophobic interactions - between non-polar side chains
e.g. 2 alkyl side chains in valine, weak VDW between induced dipoles produce non-polar regions inside the protein.
Hydrogen bonding - between polar side chains
e.g. -CH2OH in serine and -CH2COOH in aspartic acid
Ionic bonding - between side chains carrying a charge
e.g. -(CH2)4NH3+ in lysine and -CH2COO- in aspartic acid
Disulphide bridges - between sulphur atoms in the amino acid cysteine
- covalent bonds, therefore the strongest interaction.

Interactions affected by changes in the medium e.g. temperature or pH
Denatured - when a protein loses its specific tertiary structure because of the changes
e.g. egg solidifying when heated, the enzymes denature - becoming biologically inactive
Therefore intra-cellular conditions must be controlled.


Quaternary structure (association between different polypeptide chains)
Only in some proteins, when they have more than 1 polypeptide chain.

e.g. Collagen (skin and tendons), most abundant protein in the human body
- triple helix of polypeptide chains
- inter-chain h-bonds, stable rope like formation that is resistant to stretching




e.g. Hemoglobin
- 4 polypeptide chains (α + β chains) fit together tightly

Most proteins consist of only 1 polypeptide, so they wouldn't have a quaternary structure




B.2.5 Explain how proteins can be analysed by chromatography and electrophoresis.
Analysis of proteins includes determining its amino acid composition - **NOT the primary structure, which is the sequence of amino acids**
It involves chemically separating amino acids (breaking peptide bonds through hydrolysis, usually with acid), reversing the condensation reaction.

Chromatography
- good to separate and identify mixtures (especially coloured ones e.g. felt pen ink)
- amino acids = colourless in solution but has colour when treated with a locating reagent (ninhydrin)

- small sample spotted at the bottom of chromatography paper (marked in pencil, the origin)
- paper suspended in a chromatographic tank with a small volume of solvent (where the spot is above level of solvent)

- solvent rises by capillary action, passes over the spot
- spot will distribute between 2 phases: stationary phase (water in the paper) and mobile phase (solvent)
- distributes at different rates, therefore will spread out according to their different solubilities
- solvent almost reaches the top and is marked (the solvent front)
- paper is removed and developed with ninhydrin (most amino acids turn purple, distinguished as separate isolated spots are up the length of paper
 Rf = retention factor

Electrophoresis
used to separate and identify intact proteins depending on their different rates of migration towards the electrodes
- analysis based on movement of charged particles in an electric field
- amino acids carry different charges depending on the pH and can be separated when placed in a buffer solution of a known pH (if pH is lower than their isoelectric point, the amino acid is positive)
- gel medium (usually polyacrylamide)
- amino acid mixture placed in wells in the center of the gel & electric field is applied
- depends on pH of buffer, different amino acids move at different rates towards oppositely charged electrodes
- at isoelectric points, amino acids will not move because they carry no net charge
- detected by a stain or floresence under UV light and identified by their position using data tables.

B.2.6 List the major functions of proteins in the body.
Include structural proteins (for example, collagen), enzymes, hormones (for example, insulin), immunoproteins (antibodies), transport proteins (for example, hemoglobin) and as an energy source.

Function of proteins

B8 Nucleic Acids

B.8.1 Describe the structure of nucleotides and their condensation polymers (nucleic acids or polynucleotides).
Nucleic acids are polymers made up of nucleotides. A nucleotide contains a phosphate group, a pentose sugar and an organic nitrogenous base. Nucleic acids are joined by covalent bonds between the phosphate of one nucleotide and the sugar of the next, resulting in  a backbone with a repeating pattern of sugar-phosphate-sugar-phosphate. Nitrogenous bases are attached to the sugar of the backbone.
Recognise the structures of the five bases: adenine (A), cytosine (C), guanine (G), thymine (T) and uracil (U).

Includes DNA and RNA, acidic molecules found in cell nuclei (but RNA found elsewhere). Both are polymers (polynucleotide), built from nucleotide monomers.

DNA
- responsible for genetic information, and passing it onto the next generation
needs:
- to be stable, to retain precise chemical structures in cell conditions
- to contain some 'code' that stores genetic information
- to be able to be replicated - must be able to produce an exact copy of itself

RNA
- expresses genetic information
- by controlling primary structures of proteins synthesised.

Structure

Nucleotides
- building blocks of nucleic acids
- made of 3 components:

Pentose (C5) sugar: C5H10O5

DNA - deoxyribose, RNA - ribose
Difference: C2, deoxyribose lacks an -OH

Phosphate group PO4 3-, phosphoric acid H3PO4

Organic nitrogenous base

- two types: purines and pyrimidines
Purines: larger, 2 fused rings
Pyrimidines: smaller, single ring

Both have: A, G, C
Thymine is exclusively in DNA and Uracil is exclusively in RNA.
Nucleotides formed as pentose, phosphate and base are joined together by condensation reactions (water released).
Base always condensed to C1 of sugar, and phosphate to C5 (also known as 'five prime', 5', position)

DNA: a) full structure, b) shorthand form
Source: IB Chemistry Textbook

Condensation

Nucleotides --> Polynucleotides
- involves phosphate at 5' of on nucleotide and -OH group at 3' on the next nucleotide
- builds chain held together by covalent bonds between alternating sugar and phosphate residues
- bonds: phosphodiester link
- nitrogenous bases do not take part in the polymerisation, remains attached at C1

a) part of a nucleotide b) shorthand form
Source: IB Chemistry Textbook

B.8.2 Distinguish between the structures of DNA and RNA.
RNA has a single strand nucleic acid.
DNA has deoxyribose. Deoxyribose lacks an oxygen atom on C2. DNA is a double-strand nucleic acid.

Ribonucleotides in RNA
- ribose sugar
- A, G, C or U

Deoxyribonucleotides in DNA
- deoxyribose sugar
- A, G, C or T

a) ribonucleotide, b) deoxyribonucleotide
Source: IB Chemistry Textbook

B.8.3 Explain the double helix structure of DNA
The structure has two nucleic acid strands that spiral around an axis. Hydrogen bonding between specific pairs of nucleotide bases.
DNA
- double helix of 2 polynucleotides
- sugar-phosphate backbone on the outside and nitrogenous bases on the inside
- strands held together by h-bonds formed between bases
- certain base-pairings: one purine, one pyrimidine (A&T, C&G)
- A = T (2 h-bonds), C = G (3 h-bonds)

 

10 nucleotides = 1 complete turn of the helix (length of 3.4mm)
The two strands are anti-parallel, they run in opposite directions (3'-->5' and 5'-->3'). They are upside down relative to each other.
(Refering to B.8.1)
Stability: maximises hydrophobic interactions between bases in the middle of the molecules while polar, charged groups in the sugar-phosphate backbone interacts with aqueous solution
Code: sequence of bases are codes of information in the strand, with infinite varieties.
Exact replication: complementary base pairings allows this.

RNA
- single stranded polynucleotide
- constructed similarly to DNA
- also carries information in base sequence
- less stable than DNA
- usually more short-lived in the cell
- able to cross nuclear membrane (so it can move between the nucleus and cytoplasm)
3 different forms (each with a distinct role):
Messenger RNA (mRNA)
transfer RNA (tRNA)
ribosomal RNA (rRNA)
All 3 required in protein synthesis.

Central dogma of molecular biology
Source: IB Chemistry textbook

B.8.4 Describe the role of DNA as the repository of genetic information, and explain its role in protein synthesis.
DNA
- genetic material that an individual inherits from its parents
- contains all information needed for the development for the individual coded in the base sequences along its length
- expressed through controlling protein synthesis (determining the sequence of amino acids - the primary structure)
- must be translated into code for all 20 amino acids found in protein.
translated into code in 2 main steps: directs mRNA synthesis (transcription) and, through mRNA, directs protein synthesis (translation) using a triplet code.

Transcription (mRNA copies part of the DNA)
- DNA in cell nucleus, protein synthesis on ribosomes in cell cytoplasm
- relevant DNA part is copied, copy is in form of mRNA
- mRNA moves to the ribosome
- synthesis of mRNA from DNA called transcription
- when 2 DNA strands 'unzip', breaks h-bonds between the base pairs
- separate strands are templates for the other complementary strand of mRNA from ribonucleotides
- bc of the specific base pairing, complementary ribonucleotides are aligned in sequence
- DNA is copied EXACTLY
- process all controlled by enzymes
- mRNA then detaches from the DNA template and moves to the ribosome
- DNA stays in the nucleus and reforms a double helix

Transcription produces mRNA
Source: IB Chemistry Textbook

Translation (assembling protein from mRNA code)
- sequences of bases used to determine sequence of amino acids in polypeptide
- involves tRNA, like an adaptor
- one end of the tRNA recognises a specific triplet of bases (a codon) in the mRNA
- other end recognises corresponding amino acid
- codons in mRNA read sequentially, successive tRNA bring appropriate amino acids into position, they link together to form a polypeptide
- base sequence in DNA (then mRNA) determines sequence of amino acids in proteins
- genetic code: specific relationship between bases and amino acids
- triplet code with three bases specifying each amino acid
- universal code, same codon = same amino acid in all organisms
Central dogma: central information flows in one direction in cells, from DNA to RNA to protein

Transcription produces mRNA from DNA --> Translation produces polypeptide from mRNA

Semi-conservative replication of DNA
Source: IB Chemistry Textbook

B.8.5 Outline the steps involved in DNA profiling and state its use.
Include forensic and paternity cases
DNA replication: DNA makes an exact copy of itself
- occurs during cell division
- all cells in the body (except reproductive sex cells) contain an identical set of genetic information
Semi-conservative replication: replication results in new molecules that contain one strand from the parent molecule and one newly synthesised strand.

** Replication is different to transcription**

Both involve separation of DNA strands, and use of single-stranded template

Different processes, controlled by different enzymes

DNA replication: 2 identical daughter DNA molecules

Transcription: produces mRNA

Genome: unique set of DNA (except identical twins)
- identified by DNA profiling
- each cell contains ~ 3 billion base pairs, 99.9% identical in everyone, only 0.1% is unique (0.1% of ~3 billion is ~3 million base pairs, so enough for accurate identification)


DNA profiling
1. DNA extraction (from blood or the subject etc.)
- DNA cut into small pieces using restriction enzymes
- easiest place to detect the unique DNA in places where short sequences of bases are repeated numerous times, called short tandem repeats (STRs)
- test STR in multiple genome places, process is more discriminating

2. Polymerase chain reaction (PCR)
- amplifies region in the DNA by making copies
- uses sequence-specific primers to bind to the DNA that is separated into single strands
- and heat-stable version of enzyme DNA polymerase to polymerise the sections
- works around 70'C
- PCR can add up to a thousand bases per minute (million of copies of STRs)

3. Electrophoresis
- DNA fragments separated and detected
- bc of phosphate groups DNA has a negative charge
- moves towards positive terminal, distance corresponds to molecular size
- shorter fragments move further than longer fragments
- Nitrocellulose sheet used in electrophoresis treated with radiation (32P), and exposed with X-ray film.
- produces autoradiogram, dark bands shows position of fragments
- pattern seen is the DNA profile (compared to others for identification)


Applications
- to identify victims whose bodies are not present at the accident/crime scene
- forensic: to identify the suspect e.g. convicted prisoners have been exonerated (absolve from blame) by DNA evidence
- to confirm biological relationships between individuals e.g. to determine paternity, to determine family relationships for purposes of immigration or inheritance
- to determine relationships between popluations in the study of evolution, migration and ecology.

B7 Enzymes

B.7.1 Describe the characteristics of biological catalysts (enzymes).

Include: enzymes are proteins; activity depends on tertiary and quaternary structure; and the specificity of enzyme action.
They are specific for a reaction and can be individually controlled. 
Enzymes
- are proteins
- usually with several hundred amino acids
- have a tertiary structure (hence, are globular proteins, soluble in water)
- exist in cytoplasm
- 3D shape called 'conformation', determined by interaction between R groups and is essential for its function
- some made by more than 1 polypeptide, and so they have a quaternary structure (that is also important in determining their function) 
e.g. enzymes in glycolysis (respiration) are dimeric proteins and contain 2 polypeptide chains.
- some require binding of non-protein molecules for activity, called 'cofactors',
Cofactors may be organic, 'coenzymes', or inorganic, metal ions. e.g. Vitamins, many are precursors for enzymes.

Markscheme: 
- enzymes are proteins;

- temperature dependent;
- pH dependent;
- uses lock and key mechanism/ has an active site;
- works as a catalyst and lowers Ea;

B.7.2 Compare inorganic catalysts and biological catalysts (enzymes).

Enzymes are biological catalysts and control all biochemical reactions.
- increase rate of the reaction, the reactant that is catalysed is called the 'substrate'. 
- lowers Ea, so the reaction happens quicker at the same temperature
- temporarily binds to the substrate, held by weak forces of attraction forming and enzyme substrate complex.
- binding is at the enzyme's active site
- usually a much larger molecule than the substrate.

Formation of the complex depends on the compatibility ('chemical fit') of the substrate and R groups on the active site on the enzyme. Includes hydrophobic interactions, dipole-dipole attraction, hydrogen bonds and ionic attraction
- binding strains the substrate, hence aids in the breaking and forming of bonds
- once reacted it doesn't fit the active site so it detaches
- the enzyme is unchanged and can catalyze other reactions.
- all reactions are equilibrium reactions (all reversible depending on the conditions)

Lock and key mechanism
Source: IB Chemistry Textbook

Summary comparing inorganic and organic catalysts
Source: IB Chemistry Textbook

B.7.3 Describe the relationship between substrate concentration and enzyme activity.

Similar to Ch. 6 reactions
Velocity (V) used to describe the rate of reaction.
The curves in the graph shows the distinctive shape due to saturation.

Substrate concentration against rate of reaction

The graph suggests:

- low substrate concentration: rate of reaction is proportional to the substrate concentration, enzyme can bind to the substrate

- as substrate concentration increases: rate decreases, no longer proportional to the substrate concentration, some of the enzymes have their active sites occupied (by a substrate) and is not available

- high concentration: rate is constant and independent of substrate concentration, enzyme is now saturated with substrate

B.7.4 Determine Vmax and the value of the Michaelis constant (Km) by graphical means and explain its significance.

All enzymes can be saturated, but widely vary depending on the substrate concentration required to produce saturation, called Michaelis-Menten equation (Leonor Michaelis and Maud Menten)

Graph showing Vmax and Km on the rate-concentration.
Source: IB Chemistry Textbook

Michaelis-Menten kinetics features:

Mzximum velocity (Vmax)

- max velocity of the enzyme under the conditions of the experiment

- units of rate (amount of product/time)

- varies between enzymes, and pH and temperature

- rate of enzyme reactions sometimes called turnover number (the no. molecules of substrate that can be processed into products per enzyme molecule per unit of time) e.g. catalase, very fast enzyme with turnover rate up to 100 000 molecules of substrate H2O2 per second

Michaelis constant (Km)

- substrate concentration at which reaction rate is equal to one half its max value.

[S] = Km when the rate is Vmax/2

- units of concentration
- varies with pH and temperature
- information about enzyme's affinity for its substrate
- inverse relationship, low value of Km means reaction is going quickly even at low substrate concentration (higher affinity); higher value means lower affinity for its substrate.

 Rate-concentration graphs of two different enzymes (A and B)
For A, rate is higher at a lower concentration, so its Km value is lower.
Source: IB Chemistry Textbook

Differences between Km values
- determine enzyme's responsiveness to changes in substrate concentration
- low Km (e.g. hexokinase & glucose, 0.15 Km/mmoldm-3), is saturated with substrate under most cell conditions, so acts at a constant rate regardless of variations in substrate concentration
- high Km (e.g. catalase & hydrogen peroxidem, 25 Km/mmoldm-3), not normally saturated with substrate so activity is more sensitive to changes in substrate concentration.

B.7.5 Describe the mechanism of enzyme action, including enzyme substrate complex, active site and induced fit model.

Enzymes are very specific to their substrate. 
E.g. sucrose and maltose (both isomers)
- hydrolysed by sucrase and maltase
- sucrase cannot catalyse maltase breakdown, and vice versa
- specificity depends on its shape, the arrangement of R groups of the amino acids at the active site and so its precise binding ability with the substrate.

Emil Fischer - Lock and key mechanism model (above)
- recently proteomics (study of proteins and their structures/functions) suggest enzymes are less rigid structures than that model

Daniel Koshland - induced-fit mechanism
- in the presence of the substrate,  the active site undergoes some conformational changes so it is a better fit
- more dynamic relationship (amino acids R groups at the active site change into the precise binding position)

Induced-fit mechanism
Source: IB Chemistry Textbook

B.7.6 Compare competitive inhibition and non-competitive inhibition.

Activity affected by chemical inhibitors, able to modify an enzyme by binding to it.
Inhibition not always linked to illness/harm, often is important for controlling metabolic activity in healthy cells.
E.g. product of reaction sometimes acts as an inhibitor of the enzyme for its synthesis, a negative feedback loop to regulate its concentration
Product inhibition:
- product of reaction acts as an inhibitor for the first enzyme leading to its production
- concentration of product builds up and 'switches off' its own synthesis
- many amino acids synthesis are regulated this way

Product inhibition
Source: IB Chemistry Textbook

Competitive inhibitors
- bind irreversibly at the active site
- competes with substrate for the binding position
- usually has a chemical structure similar to the substrate (mimics ability to bind)
- does not react to form products, blocks active site to make it unavailable to the substrate
- increasing substrate concentration reduces inhibition, fewer inhibitors able to bind
- Vmax is not altered, still has a substrate concentration where the enzyme's full activity can be reached, but takes higher substrate concentration to reach this rate, Km increased.
e.g. malonate inhibits succinate dehydronase, converts enzyme into fumarate during aerobic respiration. Malonate and succinate have similiar structures so they are able to bind to the same active site.

Non-competitive inhibitors
- bind reversibly away from the active site

- causes conformation change that alters the active site
- increasing substrate concentration does not reduce the inhibition, the enzyme has been decommissioned and is unavailable 
- Vmax decreased, cannot be restored
- Km unchanged, because working enzymes are fully functional
Metal ions can be non-competitive inhibitors. Antibiotics (penicillin) kills bacteria by inhibiting one of their key enzymes. Many anti-cancer drugs also work the same way to block cell division in tumour. 

B.7.7 State and explain the effects of heavy metal ions, temperature changes and pH changes on enzyme activity.
Enzyme activity
- influenced by physical and chemical environment
- depends on conformational shape (to bind), hence any condition that affects its shape and binding affects catalytic property.

Temperature (Ch.6)
- rate of reaction increased by rise in temperature, due to increase in average kinetic energy of the particle
- more frequent collisions between enzyme and substrate greater than Ea (higher rate of reaction), BUT only up to a certain temperature
- effect of increase in kinetic energy is to change the conformation of the protein by disrupting the bonds and forces holding its tertiary structure
- enzyme no longer able to bind, catalytic activity decreases/ no more. (shown by the curve in a graph).
- optimum temperature: when max rate of reaction for a particular enzyme occurs. Most in the human body is around 37`C (body temperature), other organisms have enzymes with optimum temperatures closer to their ambient temperatures.

Temperature on enzyme activity
Source: IB Chemistry Textbook

Denaturation

- loss of tertiary structure

- not the loss of the covalent backbone of the protein molecule (digestion)

- irreversible (e.g. cooking an egg)

- lowering temperature causes deactivation not denaturation, prevents it from working but does not change the tertiary structure, usually reversible e.g. thawed food may spoil quick because of resumption of microbial activity as temp increases
- one of the main reasons why controlling body temperature is important, and why a few degrees change in body temperature is fatal.

pH 
- change in [H+] ions, affects equilibrium of ionization reactions
- involves R group of amino acids, change in ionic charge alters attraction forces stabilizing molecule, hence shape and binding ability
- specific pH depends on pKa and pKb of R groups (esp. in the active site), so different for each enzyme
- usually clear optimum pH value
- different enzymes, different pH is one way of controlling activity
e.g. pepsin is active in the stomach (low pH), but inactive when it moves to the intestines (more alkaline environment) where trypsin is ative
- extreme pH denatures enzymes like high temperatures

Presence of heavy-metal ions
- lead, copper, mercury, silver: POISONOUS, mainly bc of their effects on enzymes
- when they are present as positive ions, they react with sulfhydryl groups, -SH, in the side chains of cysteine in the protein, covalently bonds with the sulphur atoms and displaces a hydrogen ion.
- distrupts protein folding, changes shape of active site and binding ability, called non-competitive inhibition