TOPIC 2: FUNDAMENTAL CONCEPTS IN BIOCHEMISTRY Flashcards
Cellular energy currency
ATP
General principles of metabolism
- Fuel molecules are degraded (catabolism) and large molecules made (anabolism) step-by-step in a series of linked reactions called metabolic pathways
- The energy currency of all life is ATP
- The oxidation of pre-existing carbon molecules drives the formation of ATP
- There are only a limited number of types of reactions in metabolism
- Metabolic pathways are tightly regulated
ATP consists of
- Adenine (N-containing base)
- Sugar (ribose)
- 3 phosphates
energy is released when
ΔG is negative
energy is captured when
ΔG is positive
ΔG < 0 (i.e. negative)
- Energy is released (spontaneous, exergonic reaction)
ΔG > 0 (i.e. positive)
- Energy input required (nonspontaneous, endergonic)
Electron carrier define
also called electron shuttles, are small organic molecules that play key roles in cellular respiration.
Redox reaction
involve oxidation (loss of electrons) or reduction (gain of electrons)
- Electron carriers (NADH and FADH2) perform this function, also called coenzymes (electron carriers)
structure of NAD
nicotinamide
ribose
adenine
structure of NADP
nicotinamide
ribose
adenine
extra phosphate
NADH is derived from
Niacin
niacin also called
nicotinic acid
nicotinic acid is converted to two very useful coenzymes
o Nicotinamide adenine dinucleotide (NAD)
o Nicotinamide adenine dinucleotide phosphate (NADP)
A molecule is oxidised when
it loses electrons
A molecule is reduced when
it gains electrons
NAD+ and NADP+ are the _______ forms
oxidised
NADH and NADPH are the ______ forms
reduced
6 classes of enzyme
- Oxidoreductases
- Transferases
- Hydrolases
- Lyases
- Isomerases
- Ligases
Oxidoreductases: type of reaction and an example
Oxidation-reduction
Lactate dehydrogenase
Transferases: type of reaction and an example
Group transfer
Nucleoside monophosphate kinase (NMP kinase)
Hydrolases: type of reaction and an example
Hydrolysis reactions (transfer of functional groups to water)
Chymotrypsin
Lyases: type of reaction and an example
Addition or removal of groups to form double bonds Fumarase
Isomerases: type of reaction and an example
Isomerisation (intramolecular group transfer)
Triose phosphate isomerase
Ligases: type of reaction and an example
Ligation of two substrates at the expense of ATP hydrolysis
Aminoacyl-tRNA synthetase
What kind of electron carriers are NAD and NADP
water soluble electron carriers
FAD
Riboflavin with an adenine mononucleotide attached
FMN
Riboflavin with a phosphate attached
Unlike NAD+ and NADP+, both coenzymes FAD and FMN accept
and therefore
2H+ and 2e-
As a substrate molecule undergoes oxidation, it releases 2 hydrogen atoms.
FAD and FMN also associate with
dehydrogenases, a type of oxidoreductase (class I)
- Unlike NAD and NADP, FAD and FMN associate strongly with _______ there form a ________ group
enzymes and proteins
prosthetic group
true or false FAD and FMN are water soluble electron carriers
false
FAD and FMN function with
electron transport chains
FAD and FMN derived from
ribflavin
Concentration:
amount of solute dissolved in a known volume of solvent
concentration equation
amount/ volume
molarity equation
moles/ volume
moles equation
mass/ molecular weight
Communication is required to:
- Regulate development and organisation of cells into tissues
- Control growth and division
- Coordinate their diverse metabolic activities
best known chemical signals are called
hormones
hormones
- Any substance in an organism that carries a signal to generate some sort of alteration at the cellular level
hormones action in _____ is essential
homeostasis
key characteristics of hormones
- Key characteristics:
1. Secreted into body fluids (i.e. blood)
2. Bind to specific receptors in/on target cells
3. Initiate changes in cellular activity
4. Degraded by enzymes in target cell, liver, or kidneys
- A huge number of different hormones have been identified on the basis of their chemical structure, there are three broad types
- Peptide hormones – e.g. prolactin, insulin, glucagon
- Steroid hormones – e.g. progesterone, testosterone, estradiol
- Amino acid derivatives – e.g. adrenaline, thyroxine, triiodothyronine
growth factors
o They regulate cell proliferation and, in some cases, differentiation
- Some are quite specific, influencing only particular cell types
o Others are quite general in their effects
All growth factors that have been isolated are
proteins – this is their difference from hormones
hormones mechanism of action
- Effect on substrate concentration
- Effect on enzyme concentration
- Effect on enzyme concentration
a) Activation of pre-existing enzyme
Enzymes can be activated by either allosteric activation or covalent modification
explanation of diagram below: hormone binds to a cyclic amp (signalling molecule) and binds to a protein kinase and switches it on (this is allosteric activation – by hormone signalling) this can then phosphorylate particular enzymes in the cell (covalent modification – causing a change in enzyme activity from hormone signalling)
- Effect on enzyme concentration
b) Increase in enzyme concentration by increased rate of synthesis
A number of hormones, in particular the steroid hormones, have been shown to enhance the rate of enzyme synthesis leading to higher cellular levels of an enzyme
The hormone activates the transcriptional read-out of certain specific genes leading to an increase in the rate of synthesis of the corresponding protein
Target cells respond to a particular hormone or growth factor because they possess
specific receptor molecules
These are specialized proteins capable of binding the hormone or growth factor with
high specificity and affinity
Hormones are classified into two broad groups on the basis of their site of action:
- Those that act at the level of the cell surface – outside
o Peptide hormones and the catecholamines
o Growth factors
o Water-soluble and unable to cross the membrane
o They exert their effects on the target via intracellular secondary messengers - Those that enter the cell to exert their effects – inside
o Steroid hormones and the thyroid hormones
o Lipid soluble and can readily penetrate the membrane
o They exert their effects from within the target cell
For those agents acting at the cell surface, it has been shown that an essential target in their mode of action is the generation of an identifiable
- intracellular second messenger
o This acts to notify the cell that the first messenger (hormone/ growth factor) has bound
The first second messenger/ most important to be identified was
cyclic AMP
Cyclic AMP-mediated response
Hormone outside cell binds to receptor – causing change in shape of receptor which activates G protein (GNP) which interacts with GTP and this eventually activates a membrane bound enzyme called adenylate cyclase – which is able to take ATP and convert it into a circular molecule cyclic AMP – this is then able to allosterically activate protein kinase A within in cell – can then phosphorylate enzymes (switch them on or off) because it is a protein
Steroid hormone receptors
- Some steroid hormone receptors are located in the cytoplasm when unbound (e.g. glucocorticoid receptors)
- Others are located in the nucleus (e.g. estrogen receptors)
- Unbound receptors in the nucleus only bind weakly to DNA
- Once the steroid binds to the receptor, it acquires a high affinity for DNA
hormone mechanism of action - if lipid soluble
hormone cross cell membrane and binds to receptor changing its shape, it then binds to specific target genes on DNA those genes are then transcribed and translated
The endocrine system is controlled by the
hypothalamus and the hypophysis (pituitary gland) in the brain
Blood glucose levels in the body are tightly regulated within a range of
- 4 to 6 mM
Regulation of blood glucose levels is achieved through hormones, primarily:
o Increase: glucagon
o Decrease: insulin
Hyperglycemia
Excessive blood glucose in circulating plasma
Generally classified as BG > 10 mM
Has widespread effects on the body: CNS; heart; immune system; skin; vision
Can be caused by diabetes; eating disorders; some drugs; some diseases; and physiological stress
Hypoglycemia
Lower than normal level of circulating blood glucose
Generally classified as BG < 3.6 mM
Has wide-ranging effects: adrenergic system; CNS; neuroglycopenia
In adults, it can be caused by: diabetes’ immunological disorders; problems with the adrenal and pituitary glands; tumours
Glucose
- Glucose is the primary source of energy for all cells of the body
- Some cells can only metabolise glucose, so it is required in the body at all times
- Blood glucose levels in the body are tightly regulated within a range of 4 to 6 mM
- Regulation is achieved through hormones, primarily:
o Increase: glucagon
o Decrease: insulin
Insulin
- Polypeptide hormone, produced by beta cells of the pancreas
- Primary function is to trigger absorption of glucose form the blood into the liver, skeletal muscle and fat tissue
- Its many other effects mean that it is the main hormone regulating the use of feuls by the body
Insulin has a plasma half-life of
only 6 min
o This allows rapid changes in circulating insulin levels
o Degraded by insulinase in the liver and kidneys
Stimulation of insulin secretion
- Insulin is stored in granules in the cytosol
- Secretion of insulin and glucagon are tightly regulated to maintain glucose levels
- B-cells transport glucose via GLUT2 and phosphyorylate it via glucokinase
- As levels of phosphorylated glucose increase, it signals release of insulin and decreases release of glucagon
Inhibition of insulin secretion
- Insulin secretion is inhibited by lack of dietry fuel or during stress (e.g. infection)
- This is mediated via adrenaline
- Regulated via the sympathetic nervous system
- Allows the body to override glucose-dependent insulin production during emergencies
insulin _mechanism of action
- When insulin binds the alpha-subunits, tyosine kinase is activated and phosphorylates cellular proteins
Insulin effect on metabolism
- Increases glucose uptake into muscle cells and adipocytes - ^GLUT4
- Increases glycolysis – because will use more glucose
- Decreases hepatic gluconeogenesis – because wont be producing glucose at a time we are trying to decrease it
- Increases glycogen synthesis, decreases glycogenolysis – so glucose isnt being released
- Increases triglyceride synthesis (in adipocytes) – so cells use glucose instead
- Decreases lipolysis
- Increases protein synthesis – so its not available as a feul source, same as trigs
- Decreases protein degradation
Glucagon
- Polypeptide hormone, produced by alpha cells of the pancreas
- Primary function is to trigger the release of glucose into the blood from the liver via gluconeogenesis and glycogenolysis
- Essentially, its main role is to oppose the actions of insulin
Inhibition of glucagon secretion - Glucagon is inhibited by
elevated blood glucose
glucagon_mechanism of action
- Glucagon acts through a G protein-coupled receptor
- Binding of glucagon causes an increase in cAMP, which activates protein kinase A
- This activates a cascade of other enzymes that affect carbohydrate and lipid metabolism
Glucagon effects on metabolism
- Decreases glycolysis – want glucose in blood
- Increases hepatic gluconeogenesis – want increase glucose in liver
- Decreases glycogen synthesis, increases glycogenolysis (in liver not muscle) – don’t want to be packaging it away
- Decreases triacylglycerol synthesis – want to use this as a energy fuel instead of glucose, same for protein below
- Increases lipolysis (in adipose tissue)
- Decreases protein synthesis
- Increases protein degradation
Insulin
↓ Glycogenolysis
↓ Gluconeogenesis
↓ Ketogenesis
↓ Lipolysis
Polypeptide hormone, produced by beta cells of the pancreas
Primary function is to trigger absorption of glucose form the blood into the liver, skeletal muscle and fat tissue
Its many other effects mean that it is the main hormone regulating the use of feuls by the body
Glucagon
↑ Glycogenolysis
↑ Gluconeogenesis
↑ Ketogenesis
↑ Lipolysis
Polypeptide hormone, produced by alpha cells of the pancreas
Primary function is to trigger the release of glucose into the blood from the liver via gluconeogenesis and glycogenolysis
Essentially, its main role is to oppose the actions of insulin
