Biochemistry

Year 1 - Normal systems

anabolism

building things up, uses energy

catabolism

breaking things down, releases energy

types of proteins

structural, movement, hormones, carrier, enzymes, antibodies

features of hydrophobic amino acids

R groups are uncharged, bulky and repel water, crucial for protein folding as they tend to be buried in interior of globular proteins

features of charged amino acids

possess a positive or negative charge under physiological conditions

features of polar uncharged amino acids

R groups contain polar bonds but don’t carry net charge, can form hydrogen bonds

features of cysteine

contains a thiol (SH) group which can form disulfide bonds which stabilises protein structure

features of glycine

smallest amino acid with a hydrogen atom R group, small size allows flexibility in protein structure

features of proline

cyclic structure where R group is bonded back to its amino group

primary protein structure

unique sequence of amino acids in a polypeptide chain determined by the genetic code

secondary protein structure

folded structures that form within a polypeptide due to hydrogen bonding between backbone atoms (not R groups) which can be an alpha helix or a beta pleated sheet

tertiary protein structure

overall 3D shape of a single polypeptide chain which is stabilised by hydrophobic interactions, ionic bonds, hydrogen bonds, disulfide bonds and metal ion coordination

quaternary protein structure

interactions between different protein chains which may be identical or different which form a more complex 3D structure

methods to determine protein structure

mass spectrometry, x-ray crystallography, cryo-electron microscopy, NMR and AlphaFold

mass spectrometry

organic analysis method used to determine the amino acid sequence of a polypeptide

x-ray crystallography

a traditional analysis method involving crystallising a protein then firing x-rays at it to deduce its 3D structure from the diffraction pattern

AlphaFold

a revolutionary AI system that predicts the 3D shape of a protein from its amino acid sequence

3 types of proteins based on shape and solubility

globular, fibrous and membrane

globular proteins

compact, spherical and soluble proteins which typically have a hydrophobic core and hydrophilic surface allowing them to interact with water, generally interact with other small molecules

fibrous proteins

elongated, insoluble proteins found in multiple strands which are bigger than globular proteins

fibrous protein examples

keratin, fibroin and collagen

membrane proteins

proteins embedded within or associated with cell membranes which sit within the lipid bilayer and transmit molecules and signals in and out of cells

diseases caused by collagen defects

hereditary equinal regional dermal asthenia, junctional epidermolysis bullosa, both cause fragile skin

prion

an infectious protein that can cause fatal neurodegenerative diseases

prion disease mechanism

an infection causes the host’s normal prion protein which is rich in alpha-helices to switch to an abnormal misfolded conformation which is rich in beta-sheets and is highly stable so resistant to degradation. The abnormal protein aggregates into insoluble fibres in the brain which leads to neuronal cell death and characteristic spongiform changes

examples of prion diseases

scrapie and bovine spongiform encephalopathy/ mad cow disease

enzyme

a biological catalyst which increases the rate of a chemical reaction without being consumed in the process by decreasing the activation energy of a reaction

how enzymes lower the activation energy of a reaction

bringing substrates together in the correct orientation, excluding water from the active site, stabilising the transition state, transferring protons

uses of enzymes

crucial for biological processes, disease diagnosis, drugs target enzymes

active site

region of an enzyme that binds to the substrate and forms the catalytic site

induced fit model

the substrate binds to the active site and slightly changes its shape when it forms an enzyme-substrate complex

isosteric enzyme

enzyme with one active site that increases reaction rate proportionally to substrate concentration until enzyme becomes saturated

allosteric enzyme

enzyme with multiple active sites (typically multi-subunit protein) allowing the enzyme to bind to several substrates which makes it more efficient the more it binds to due to the conformational change caused by the substrate binding

enzyme co-operativity

when the binding of a substrate to one active site on an enzyme affects the activity of the enzyme’s other active sites

features of allosteric enzymes

multi-subunit, bind other ligands at allosteric sites, can be activated or inhibited by allosteric ligands, often control key reactions in major pathways

allosteric activator

molecule that binds to an allosteric site on an enzyme which causes a conformational change making the active site more accessible/active, activating the enzyme

allosteric inhibitor

molecule that binds to an allosteric site on an enzyme, making it inactive

feedback inhibition

a common mechanism where the end product of a metabolic pathway acts as an allosteric inhibitor for an enzyme which prevents the buildup of intermediates and conserves resources

competitive inhibitor

a molecule that binds to an enzyme’s active site and competes with the substrate for binding

non-competitive inhibitor

a molecule that binds to an allosteric site on an enzyme which causes a conformational change that reduces the enzymes catalytic efficiency

uncompetitive inhibitor

a molecule that binds to an enzyme-substrate complex causing a major conformational change

factors affecting enzyme activity

substrate concentration, enzyme concentration, temperature, pH, post-translational modification, coenzymes and cofactors

post-translational modification

changes made to a protein after its synthesis which can activate or deactivate enzymes

phosphorylation

the reversible covalent attachment of a phosphate group to specific amino acid R groups which can make an enzyme active or inactive

proteolytic activation

the irreversible hydrolysis of peptide bonds in an enzyme to remove a protein group to form the active form of an enzyme from an inactive precursor

coenzymes and cofactors

small non-protein units that assist enzymes in catalysis by carrying electrons or functional groups

proteases

enzymes that break down proteins by hydrolysing peptide bonds

serine protease

protease with a catalytic triad of three amino acids in its active site (serine, histidine and aspartate), serine’s hydroxyl group becomes highly nucleophilic and attacks the peptide bond

cysteine proteases

proteases which use a cysteine residue in their active site for catalysis

aspartic proteases

proteases which use aspartate residues in their active sites

metalloproteases

proteases which require a metal ion in their active sites for catalysis

isozymes

different forms of an enzyme which catalyse the same reaction but are encoded by different genes and may be found in different tissues

multi-enzyme complexes

different enzymes that are physically associated to perform a series of sequential reactions in order to increase the overall reaction rate, minimize side reactions, ensure the intermediate is readily available for the next substrate and to provide an energy efficient arrangement

starch

a polysaccharide of maltose made up of amylose and amylopectin

glycosylation

the process of adding sugars to proteins and lipids

what is chitin made up of?

polymerised N-acetyl glucosamine

glycogen metabolism in the liver

glucagon is released which causes phosphorylase kinase to activate glycogen phosphorylase to catalyse the conversion of glycogen to glucose 1-phosphate, then glucose 6-phosphate to glucose to maintain blood glucose

glycogen metabolism in muscle

insulin is released which causes phosphorylase kinase to activate glycogen phosphorylase to catalyse the conversion of glycogen to glucose 1-phosphate and then glucose 6-phosphate which enters glycolysis to form ATP allowing exercise to occur

von Gierke’s disease

glucose-6-phosphatase deficiency means that the animal’s liver cannot convert glucose-6-phosphate to glucose which results in blood hypoglycaemia and an enlarged liver due to excessive glycogen storage

Pompe’s disease

deficiency in lysosomal glucosidase causes accumulation of glycogen inside lysosomes as there is no glucosidase to break down maltose once glycogen is converted to maltose by beta-amylase, this causes reduced blood sugar and an enlarged liver

Cori’s disease

deficiency of debranching enzyme which results in shorter and more frequent glycogen branches causing hypoglycaemia and hepatomegaly (enlarged liver)

type I diabetes

an autoimmune response selectively destroys islet cells which prevents the animal from producing insulin, in dogs immune system destroys beta cells and in cats amylin is deposited in pancreas

pregnancy toxaemia in sheep

hypoglycaemia caused by high metabolic demands in last 6 weeks in pregnancy or other stresses

glycolysis

glucose is split into 2 pyruvate molecules, 2 net ATP and 2 NADH in the cytoplasm

gluconeogenesis

glucose synthesis from non-carbohydrates which occurs in the liver and kidney cortex

why are fluoride tubes used for glucose collection?

fluoride stops red cells from metabolising glucose to maintain a constant glucose concentration

importance of the Krebs cycle

energy production, electron donors to enter oxidative phosphorylation, biosynthesis provides precursors for amino acids, fatty acids, steroids and haem synthesis

function of anaerobic glycolysis

to regenerate NAD+ which allows glycolysis to continue

function of aerobic glycolysis

to produce pyruvate to be converted to acetyl CoA to enter the Krebs cycle

oxidative phosphorylation

the metabolic pathway in which the mitochondria in cells use their structure, enzymes and energy released by the oxidation of nutrients to reform ATP

sodium fluoroacetate

a pesticide which binds to coenzyme A, reacts with citrate synthase and produces a metabolite that inhibits aconitase, making it poisonous to humans and animals

cyanide

a chemical that binds to the iron in cytochrome c oxidase in complex IV and prevents transfer of electrons to oxygen, disrupting the electron transport chain and preventing ATP generation

nitrogen cycle

the process by which nitrogen is converted between its various chemical forms

nitrate reductase

enzyme that catalyses the conversion of nitrate ions to nitrite ions and water

nitrite reductase

enzyme that catalyses the conversion of nitrite ions to ammonia and water

glutamate dehydrogenase

enzyme that converts glutamate to ketoglutarate and ammonia

glutamine synthase

enzyme that converts glutamate and ammonium to glutamine and water

glutamate

the main excitatory neurotransmitter in the central nervous system

glycine

inhibitory neurotransmitter in parts of the brain and spinal cord

aspartate

a rare excitatory neurotransmitter

transamination

the transfer of an amino group from one molecule to another

tryptophan

essential amino acid that forms a precursor for serotonin and a neurotransmitter, used as a sleep aid and antidepressant

leucine

an essential branched-chain amino acid vital for protein synthesis and muscle health

glucogenic amino acids

amino acids that are broken down to TCA cycle intermediates

ketogenic amino acids

amino acids that are broken down to acetyl CoA or acetoacetate

deamination

process of removing an amino group from an amino acid to form ammonia

what happens to free ammonium ions produced by transamination and deamination in the liver?

they enter the urea cycle by conversion to carbamoyl phosphate

transport of amino acids from muscle to liver

ammonium ions produced when amino acids are broken down are converted to alanine or glutamine which are transported through the blood to the liver where alanine is converted to glutamate and deaminated

ammonotelic

animal that can directly excrete ammonium (aquatic animals)

ruminant nitrogen metabolism

proteins are hydrolysed to amino acids by ruminal microbes and the proteins that are not are digested in the small intestine, the ruminal microbes then use the amino acids for their own protein synthesis or degrade them further to ammonia

which species cannot reduce nitrate to ammonia?

animals

methionine

an essential amino acid crucial for protein synthesis, metabolism, tissue growth, and detoxification

why is alanine and glutamine found in higher concentrations in blood plasma?

they are used for the transport of nitrogen to the liver prior to the breakdown of the urea cycle

glutamate and GABA regulation

glutamate is the primary excitatory neurotransmitter and GABA is inhibitory so the two neurotransmitters regulate brain activity by maintaining a balance between excitation and inhibition

ureotelic nitrogen metabolism

process in which certain animals excrete nitrogenous waste primarily in the form of urea, it is excreted by the kidneys and in saliva and sweat and in ruminants excreted into the gastrointestinal system where it can be reused for amino acid biosynthesis

causes of a higher blood urea nitrogen

increased protein catabolism, increased protein digestion, decreased glomerular filtration rate

causes of a lower blood urea nitrogen

decreased protein intake, increased protein synthesis, increased excretion rate, decreased urea production

blood urea nitrogen

a test that measures the amount of urea in blood

uricotelic nitrogen excretion

excreting nitrogen as uric acid by purine degradation, happens in birds and non-aquatic reptiles and conserves water