Cellular Metabolism Flashcards
What are the main objectives of metabolism?
Breakdown of foods to use as energy
▫ We mainly use carbohydrates and lipids as energy substrates –
glucose, fatty acids etc.
* Breakdown of foods and cellular recycling for building new
proteins, nucleic acids, lipids and carbohydrates
▫ Formation of new molecules
* Processes that result in the elimination of cellular waste products
What are the two types of metabolism?
- Catabolism
- Anabolism
What is Catabolism?
▫ Catabolic processes break down complex molecules to simpler one
▫ Generally exergonic
They release more energy than they consume
What is Anabolism?
▫ Anabolic processes build larger structures from simpler one
▫ Endergonic
They consume energy
What is ATP?
- Cellular energy
- ATP provides most of the energy required for metabolic reactions in the cell.
- Each cell contains around 1 billion molecules of ATP.
- Each ATP molecules lasts less than 1 minute.
What is ATP used for?
- Powering Metabolic reactions in the cell
What is oxidation?
- result in a change to the original molecule or substance.
- Oxidation can occur in three ways:
▫ The addition of oxygen e.g. C + O2 → CO2
▫ Removal of electrons from an atom or molecule
▫ Removal of hydrogen - Usually exergonic - releases energy
What is reduction?
- result in a change to the original molecule or substance.
Reduction can also occur in three ways
▫ Removal of oxygen
▫ Addition of electrons to a molecule
These electrons are known as ‘high energy electrons’
▫ Addition of hydrogen - Usually endergonic – require and store energy
What is a endergonic reaction?
requires and stores energy.
What is an exergonic reaction?
Usually releases energy.
What is NAD?
- Nicotinamide adenine dinucleotide - NAD
▫ From Vit B3 – niacin
What is FAD?
- Flavin adenine dinucleotide – FAD
▫ From Vit B2 – riboflavin
What is a cofactor?
Non-protein chemical compound or metallic ion that is required for an enzyme’s role as a catalyst.
NAD redox states
- Oxidised NAD (NAD+) is reduced to NADH + H+
▫ NAD gains a hydride ion (H-)
Hydrogen atom with an additional electron
▫ 2 hydrogen ions (2H+) and 2 electrons (2e-)
▫ 1of the hydrogen ions is released
[NAD+ + 2H+ + 2e-] Oxidised & low energy <—->
[NADH + H+] Reduced & High energy
FAD redox states
Oxidised FAD is reduced to FADH2
* FAD gains:
▫ 2 hydrogen ions (2H+) and 2 electrons (2e-)
[FAD + 2H+ + 2e-] Oxidised & low energy <——>
[FADH2] Reduced & high energy.
What is the preferred energy substrate for ATP production?
Glucose
What are dietary carbohydrates hydrolysed to?
monosaccharides (mostly glucose 80%, also fructose and galactose, liver converts the galactose and most fructose to glucose)
How is glucose used in the body?
- Glucose can be oxidised to form ATP
- Additional metabolic pathways for glucose include:
▫ Formation of amino acids
▫ Formation of glycogen (glucose polysaccharide)
▫ Synthesis of triglycerides by the liver
Storage in adipocytes
How does glucose enter the cells?
- Entry via GluT molecules on most cells of the body – facilitated
diffusion
▫ GluT = Glucose Transporters
▫ Cell membrane proteins - Neurons and hepatocytes posses GluT 2 & 3 respectively
- Skeletal muscle and adipose cells produce and insert GluT 4
molecules in response to high insulin concentrations
▫ These two cell types make up a large portion of us as organisms
>60% in most individuals
How is glucose catabolised?
Glucose is phosphorylated once inside the cell
▫ Prevents glucose leaving the cell
* Glucose catabolism can then proceed
* Four distinct stages:
▫ Glycolysis
▫ Formation of acetyl coenzyme A
▫ Krebs cycle reactions
Krebs cycle AKA: citric acid cycle (CAC) or tricarboxylic cycle (TCA)
▫ Electron transport chain reactions
What is glycolysis?
- Pathway of 10 reactions in the cytosol of cells
- One molecule of glucose (C6H12O6) is oxidised to produce:
▫ 2 molecules of ATP
▫ 2 molecules of pyruvic acid
▫ 2 molecules of reduced NAD (NADH)
Contain energy - This process does is also used by anaerobic organisms
What is acetyl coenzyme A and how does it form?
- molecule that participates in many reactions in protein, carbohydrate and lipid metabolism.
- Intermediate stage that oxidises pyruvic acid
for entry into the Krebs cycle - In mitochondria, pyruvic acid produces:
▫ 1 molecule of CO2
▫ 1 molecule of reduced NADH + H+
Contains energy
▫ 1 molecule of acetyl coenzyme A
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What is the Krebs cycle?
- Acetyl CoA is oxidised in the mitochondrial
matrix - Primary aim is to produce
▫ NADH
▫ FADH2
Used in the electron transport chain - Also produces:
▫ ATP (little)
▫ CO2
What is oxidative phosphorylation?
- Have you ever wondered why we need to breathe oxygen?
- O2 is involved in the final step of the electron transport chain
- Oxidative phosphorylation involves two connected processes:
▫ Passage of electrons along the electron transport chain
▫ Pumping of hydrogen ions - chemiosmosis
What is the electron transport chain?
- Series of electron carriers on the inner mitochondrial membrane
- 1000’s of transport chains per mitochondrion
▫ Due to folded inner membrane (cristae) increasing surface area - Carriers are systematically reduced and oxidised
▫ Exergonic reactions produce energy - Last electron acceptor is O2
- Electron carriers are proteins found in the inner mitochondrial
membrane - They are known as protein complexes I – IV
- Also contain two key additional factors:
▫ Coenzyme Q10
▫ Cytochrome C complex - Electrons are supplied by the two main products of the Krebs
cycle – high-energy electron carriers:
▫ NADH
▫ FADH2
How many protons does Complex 1 pump out?
4
How many protons does complex II pump out?
0
How many protons does Complex III pump out?
4
How many protons does Complex IV pump out?
2
What does gluco and glyco mean?
Sugar or glucose derivative.
Gluco - usually refers to the monosaccharide glucose.
Glyco - usually refers to the polysaccharide glycogen.
What does neo mean?
new
What does genesis mean?
formation of
What does lysis mean?
to split or break apart
What are the two main glucose anabolic processes?
- Glycogenesis
▫ Formation of glycogen – polysaccharide - Gluconeogenesis
▫ Synthesis of new glucose molecules
What is Glycogenesis?
- We can store glucose in the form of its polysaccharide glycogen
▫ In the liver and skeletal muscle - Total storage is around 500g
▫ Skeletal muscle (75%)
▫ Liver (25%) - Glycogenesis is driven by the hormone insulin
- When glucose is needed, we reverse the process
▫ Glycogenolysis
What is Gluconeogenesis?
- When glycogen stores are depleted, your body creates new
glucose molecules
▫ Occurs mainly in the liver
▫ Known as gluconeogenesis - Proteins and lipids are catabolised
- To make new glucose molecules we use:
▫ Glycerol from triglycerides
▫ Lactic acid
▫ Certain amino acids – mostly alanine and glutamine - Gluconeogenesis is initiated by two hormones
▫ Cortisol – major glucocorticoid
▫ Glucagon from pancreatic α cells - Cortisol also initiates the catabolism of proteins
▫ Increases the available pool of amino acids - Also involves the release of thyroid hormones (T3 and T4)
▫ Mobilise proteins
▫ Also stimulate mobilisation and degradation of lipids
How are lipids stored?
- in the form of triglycerides.
What is lipolysis?
- The fatty acids from triglycerides can be oxidised and used to
produce ATP - First step is removing the fatty acids from the glycerol molecule
▫ Lipolysis - Glycerol is converted into glyceraldehyde 3-phosphate
Converted into glucose if cellular ATP is high
Catabolised to pyruvic acid if ATP is low
What is beta oxidation?
- Fatty acids are essentially long hydrocarbon chains
▫ Energy dense - Catabolism starts in the mitochondrial matrix
- Beta oxidation involves the removal of two carbons atoms from
the fatty acid at a time - These are attached to coenzyme A to form acetyl coenzyme A
(acetyl CoA)
What is a saturated fatty acid?
- Saturated fatty acid
▫ Carbon chain is ‘saturated’ with hydrogen atoms
▫ All single covalent bonds
No C-C double covalent bonds
What is an unsaturated fatty acid?
- Unsaturated fatty acid
▫ Carbon chain contains one or more double covalent bonds
▫ Monounsaturated – one double bond
▫ Polyunsaturated – two or more double bonds
How many carbons are on a short chain fatty acid?
5 or less
How many carbons are on a medium chain fatty acid?
6-12
How many carbons are on a long chain fatty acid?
13-21
How many carbons are on a very long chain fatty acid?
22 or more
What is an omega fatty acid?
Omega refers to the end of
the carbon chain
▫ Methyl end (CH3)
What does the number on the omega fatty acid indicate?
- The number refers to the
number of carbons from the
omega end where the first
double bond occurs
What is lipid anabolism?
- Synthesis of lipids is known as lipogenesis
- Takes place in the liver and adipocytes
- Initiated by insulin
- Occurs in response to a positive energy balance
▫ More energy consumed than used - Carbohydrates, proteins and fats are all converted into triglycerides and stored
How are lipids transported?
- Lipids are non-polar and hydrophobic
- They must be encased in a hydrophilic shell before transportation
in blood can occur - This occurs in two locations
▫ Intestines form chylomicrons for dietary lipid transport
▫ Liver produces very low density and low density lipoproteins (VLDL
and LDL)
▫ Liver and intestine produce nascent high density lipoprotein
Becomes HDL
How are proteins metabolised?
Both carbohydrates and lipids can be stored in the body
* Dietary protein is broken down to amino acids
* These are not stored
▫ Used to build proteins or oxidised to make ATP
* Excess amino acids are converted to glucose or triglycerides
How are proteins catabolised?
- Protein catabolism is driven mainly by the glucocorticoid cortisol
- Proteins are broken down into their individual amino acids
- The amino acids can then be:
▫ Converted into different amino acids (in some cases)
▫ Used to construct new proteins
▫ Converted to fatty acids, ketone bodies or glucose
▫ Oxidised to make ATP
Via conversion to acetyl CoA
How does protein anabolism work?
- We have seen in the previous slide the importance of proteins
- The human body contains 20 different amino acids
- 9 of these are known as essential amino acids
▫ We either cannot synthesise them cannot synthesise enough - ‘Complete’ dietary proteins supply all 20 amino acids in sufficient quantities
What are the essential amino acids?
- Tryptophan
- Methionine
- Valine
- Threonine
- Phenylalanine
- Leucine
- Isoleucine
- Lysine
- Histidine
What are the non-essential amino acids?
- Alanine
- Arginine - possibly essential during infancy
- Asparagine
- Cysteine
- Glutamic acid
- Glutamine
- Glycine
- Proline
- Serine
- Tyrosine
What is the human proteome?
- Humans can produce between 80,000 to 400,000 different
proteins*
▫ Many are variants of the same protein
▫ Coded for by gene variants known as alleles - This is from around 20,400 protein-coding genes
- Not all proteins produced at any one time
- Some only due to disease etc.
What is deamination?
Involves the removal of the amino group from the amino acid in
the liver or kidney
What is Transamination?
- Nitrogen is a precious commodity in biological organisms
▫ Required for protein and nucleic acid production - Transamination involves recycling nitrogen to produce:
▫ Non-essential amino acids
▫ Prevent ammonia production and excretion of nitrogen from kidneys - Uses enzymes called transaminases
- Transfers an amino group to a keto acid
How are metabolic reactions balanced?
- Metabolic reactions are balanced between catabolic and anabolic
▫ e.g. adenosine triphosphate (ATP) is produced by anabolic reactions
▫ When ATP is broken down to adenosine diphosphate (ADP) + P energy is released
▫ Energy is used to re-attach a phosphate group to ADP to form ATP (phosphorylation)
ADP + ℗ + energy = ATP
Do oxidative and reduced states occur simultaneously?
-Known as REDOX cycle
Extra facts about NAD and FAD
- Both have oxidative and reduction states.
- Both are cofactors that are crucial for energy production.
- They can be reduced by accepting hydrogen and electrons.
- They are then oxidised and the released hydrogen and electrons are used to produce ATP.
What is the importance of oxidation?
- Oxidation is used in the production of ATP in mitochondria
- Oxidative phosphorylation involves the removal of electrons from substrates
- These electrons are passed down the electron transport chain
- Involves O2 as a final step
- Very efficient process of producing ATP
What is the role of NADH in the electron transport chain?
NADH is oxidised and donates 2 electrons to protein complex I
* The electrons are passed between the other complexes
* As this happens, each protein complex pumps hydrogen ions
(protons) into the intermembrane space – 10 in total
▫ Complex I pumps out 4 protons
▫ Complex III pumps out 4 protons
▫ Complex IV pumps out 2 protons
What is the role of FADH2 in the electron transport chain?
- FADH2 is oxidised and donates 2 electrons to protein complex II
- These are passed to coenzyme Q10 and then on to complex III
and IV - Again, protons are pumped but complex I is missed so only 6
protons are pumped into the intermembrane space
▫ Complex III pumps out 4 protons
▫ Complex IV pumps out 2 protons
How is ATP produced?
- The protons pumped by the protein complexes collect in the
intermembrane space - This creates a high concentration gradient of H+
- These pass down their electrochemical gradient and into the
matrix through the final protein
▫ ATP synthase/synthetase - ATP synthase acts as a generator and the flow of protons powers
the phosphorylation of ADP to ATP
Why is oxygen required?
The electrons re-enter the mitochondrial matrix
* Here, they bind with O2 and protons that have passed through
ATP synthase to form H2O
What is the preferred energy substrate for the production of ATP?
Glucose
How are lipids metabolised?
- Lipids are the primary energy storage molecules
▫ 98% of stored energy reserves are in the form of triglycerides - Two main reasons for this
▫ Over twice as energy-dense per gram compared to carbohydrates or
proteins
▫ Hydrophobic – cells do not exert osmotic pressure - Packed into adipocytes and found in the subcutaneous layer
(50%) and as visceral fat
How are fatty acids catabolised?
Acetyl CoA then enters the Krebs cycle
* Very high energy content
* Palmitic acid (below) contains 16 carbon atoms
* If fully oxidised through the Krebs cycle and electron transport
chain can yield 129 ATP molecules
What are the types of fatty acids?
- Fatty acids can be classified in many ways
- Most commonly, these are:
▫ Whether they are saturated or unsaturated
▫ Length of the hydrocarbon chain - These factors are important to our health and wellbeing
▫ Oxidised fatty acids are involved in the development of
atherosclerosis
▫ Lipid-derived inflammatory mediators are dependant of the type of
fatty acid
