Hormones - Control of Metabolism

Question 1

Why does a cell need to control metabolism?

Answer 1

Use the most appropriate available food source (carbohydrate priority)
Balance catabolic and anabolic reactions
Avoid unnecessary futile cycles (opposing pathways working at the same time e.g. synthesis and breakdown)
React to a changing environment

Question 2

What are signalling pathways?

Answer 2

There is a signal/stimulus
An extracellular signal molecule binds to a receptor protein
This activates intracellular signalling proteins (secondary messengers) to activate target proteins (in order to amplify the response) such as enzymes to alter: metabolism, gene expression etc… (phenotypic change)
This will often feedback to control the pathway

Question 3

How does the cell type determine the response?

Answer 3

The target cell need to recognise the messenger and therefore must have the appropriate receptor
The wrong receptor means it won’t respond

Question 4

How do same/different signals work with effectors?

Answer 4

The signal can bind to receptor 1 = secondary messenger(s) = effector 1 and response 1
But the signal may be able to bind to another receptor leading to another secondary messenger

2 different signals come in to 2 different receptors - but they both activate the same second messenger, to give the same response

Question 5

What are the major receptor types?

Answer 5

G-protein coupled receptors - they produce a range of 2nd messengers
Enzyme-linked receptors - they have enzyme activity (Tyr-kinase)

Question 6

What are the types of signal transduction?

Answer 6

Switches
Phosphorylation
Transcriptional regulation

Question 7

Describe signal transduction: switches?

Answer 7

All aspects of signalling require a molecular switch i.e. Change the conformation of a protein by modifying it = a switch to alter the activity
Both exchanges are very controlled signalling
Both happen for only seconds

Question 8

How do the major receptor types respond to switches?

Answer 8

Enzyme-coupled reactions:
When they aren’t activated they will have no post-translational modification
Upon activation/binding/interaction they will be post-translationally modified
Inactive = unphosphorylated
Active = phosphorylated
This is carried out by a protein kinase using ATP

G-proteins:
Also use post-translational activation but not of the receptors but of the coupled G-protein
Inactive = bound by GDP
Active = bound by GTP in it’s place
They switch using GTP hydrolysis using accessory proteins that facilitate this

Question 9

What is signal transduction - phosphorylation?

Answer 9

This is a universal means to control substances within cells (uni and multicellular)
Kinase adds a gamma phosphate
Phosphatase removes phosphate
Change in phosphorylation can activate/deactivate an enzyme
Kinases and phosphatases often regulated by phosphorylation

Question 10

What is phosphorylated in signal transduction phosphorylation?

Answer 10

It is three amino acids that are phosphorylated
Mainly serine and threonine but a subsection are tyrosine
These amino acids contain a OH group in their R group, which is why they are susceptible to the phosphorylation

Question 11

What is signal transduction - transcriptional regulation?

Answer 11

Due to receptor binding, 2nd messenger and phosphorylation
This leads to activation or deactivation of transcription factors
Genes can then be switched on or off and a new pathway is formed or removed
This allows cells to adapt to a change in their environment (e.g. Change in fuel source)

Question 12

What is the range of cell signalling?

Answer 12

The changes can happen locally or across a whole organism
Autocrine secretion - a cell is signalling to itself
Paracrine secretion - a cell is signalling to a cell within its surrounding locality
Endocrine secretion - a cell is signalling to a cell to another cell in a completely different organ/system for example

Question 13

Describe the endocrine system?

Answer 13

This has developed to ensure we can adapt to changes within the environment and respond accordingly
It is made up of ductless glands that release chemical messengers (hormones) into the bloodstream
Hormones regulate all aspects of metabolism

Question 14

What are the functions of endocrine hormones?

Answer 14

Maintain homeostasis
Respond to a wide variety of external stimuli - preparation for fight/flight
Various cyclic and developmental programs - maturation, menstral cycle and pregnancy

Question 15

What are some examples within in the endocrine system?

Answer 15

Pancreatic Islet hormones - controls fuel metabolism

Adrenaline and noradrenaline - prepare the body for action

Question 16

How do the pancreatic Islet hormones work?

Answer 16

The Islets of Langerhans, have 3 types of cells that each secrete a polypeptide horomone:
α cells secrete glucagon (29 residues) - promotes release of glucose
β cells secrete insulin (51 residues) - promotes uptake of glucose
δ cells secrete somatostatin (14 residues) - used to regulated fuel metabolism during exercise, inhibits insulin and glucagon

Question 17

How to the adrenal glands work?

Answer 17

They consist of 2 tissues, the medulla and gluandular cortex
It synthesises 2 active catecholamines: adrenaline and noradrenaline (both synthesised form tyrosine)
They are received by
α and β adrenergic receptors

Question 18

What are the types of hormone?

Answer 18

Peptide/protein - e.g. Insulin
Steroids - e.g. Cortisol
Lipids - e.g. Eicosanoids
Amino acid derivatives - e.g. adrenaline

Question 19

Describe steroid hormones?

Answer 19

They all derive from Cholesterol and differentiated by the different steroid hormones
Made in mitochondria and smooth ER being released immediately as there is no storage mechanism for these hormones

Question 20

What are the categories of steroid hormones?

Answer 20

Can be subdivided into a number of classes:
Glucocorticoid - e.g. Cortisol
Androgen - e.g. Testosterone
Mineralocorticoids - e.g. Aldosterone (they control salt/mineral balances)
Estrogen - e.g. Beta-estradiol

Question 21

How are steroid hormones transported?

Answer 21

These steroid molecules are extremely hydrophobic
Therefore the steroids are bound to protein carriers (essentially stored this way in the blood) in an inactive conformation - the glycoproteins are called transcortin
They become active only upon release, at a target cell

Question 22

What is significant about steroid receptors?

Answer 22

Steroids have an intracellular receptor and don’t fall into the nice categories of the G-protein coupled receptors or the enzyme-linked receptors
Because it is hydrophobic it doesn’t need a receptor on the cell surface membrane, when it can simply pass through the plasma membrane

Question 23

What is the action of steroid horomones?

Answer 23

Hormone diffuses through phospholipid bilayer & into cell
Binds to receptor and alters gene expression (this is in the cytoplasm or nucleus, the receptor molecule acts as a receptor and a transcription factor)
Therefore steroid hormones can act directly as transcription factors
New mRNA is formed & directs synthesis of new proteins
New protein alters cell’s activity

This is slow as new hormone often needs to be synthesised before it can have an effect due to lack of storage

Question 24

Describe amines, peptides and proteins as hormones?

Answer 24

Peptide - small chain of amino acids 3-191, they are the most common hormone type and are water soluble/lipophobic
Amines - altered amino acids, usually hydrophilic and act like peptides e.g. catecholamines

Question 25

Describe peptide hormone synthesis?

Answer 25

They are made as precursors that undergo a processing within the ER and Golgi, in order to cleave parts of an inactive precursor hormone to the active hormone

1. mRNA binds to a pre-hormone peptide chain, this chain is directed into the ER
2. Enzymes in the ER chop off the signal sequence = inactive pro-hormone
3. Pro-hormone moves from the ER to the Golgi
4. Secretory vesicles take the pro-hormone and enzymes chop it into more active peptides
5. The secretory vesicles releases its contents via exocytosis into extracellular space
6. The hormone moves into circulation for transport to the target

Question 26

How are peptide hormones stored/moved?

Answer 26

Peptide hormones circulate in the blood and do not require transport proteins (which differs with steroid hormones)

Question 27

What is the peptide hormones mode of action?

Answer 27

Peptide hormones cannot diffuse through the plasma membrane
They activate cell surface receptors and initiate signal transduction cascades
The effects of peptide hormones are often rapid and transient

Question 28

How is hormone secretion controlled?

Answer 28

Feedback control
Neural control - neural stimuli can evoke or suppress hormone secretion
Chronotropic control - certain patterns of hormone secretion appear to be dictated by rhythms e.g. The body clock

Question 29

Describe feedback control/loops?

Answer 29

Negative feedback - the response counteracts the stimulus, shutting of the response loop
Positive feedback - the response reinforces the stimulus the parameter further from the set point (an outside factor is required to shut off the feedback cycle)

Question 30

Give an example of negative feedback?

Answer 30

Testosterone is activated by GnRH and LH
But then once produced it is testosterone that then inhibits GnRH and LH in a negative feedback loop
Anabolic steroids are testosterone agonists, leading to breakdown of the gland and therefore infertility