Cellular Metabolism Flashcards

1
Q

What are the main objectives of metabolism?

A

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

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2
Q

What are the two types of metabolism?

A
  • Catabolism
  • Anabolism
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3
Q

What is Catabolism?

A

▫ Catabolic processes break down complex molecules to simpler one
▫ Generally exergonic
 They release more energy than they consume

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4
Q

What is Anabolism?

A

▫ Anabolic processes build larger structures from simpler one
▫ Endergonic
 They consume energy

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5
Q

What is ATP?

A
  • 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.
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6
Q

What is ATP used for?

A
  • Powering Metabolic reactions in the cell
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7
Q

What is oxidation?

A
  • 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
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8
Q

What is reduction?

A
  • 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
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9
Q

What is a endergonic reaction?

A

requires and stores energy.

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10
Q

What is an exergonic reaction?

A

Usually releases energy.

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11
Q

What is NAD?

A
  • Nicotinamide adenine dinucleotide - NAD
    ▫ From Vit B3 – niacin
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12
Q

What is FAD?

A
  • Flavin adenine dinucleotide – FAD
    ▫ From Vit B2 – riboflavin
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13
Q

What is a cofactor?

A

Non-protein chemical compound or metallic ion that is required for an enzyme’s role as a catalyst.

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14
Q

NAD redox states

A
  • 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
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15
Q

FAD redox states

A

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.

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16
Q

What is the preferred energy substrate for ATP production?

A

Glucose

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17
Q

What are dietary carbohydrates hydrolysed to?

A

monosaccharides (mostly glucose 80%, also fructose and galactose, liver converts the galactose and most fructose to glucose)

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18
Q

How is glucose used in the body?

A
  • 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
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19
Q

How does glucose enter the cells?

A
  • 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
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20
Q

How is glucose catabolised?

A

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

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21
Q

What is glycolysis?

A
  • 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
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22
Q

What is acetyl coenzyme A and how does it form?

A
  • 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
    23
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23
Q

What is the Krebs cycle?

A
  • 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
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24
Q

What is oxidative phosphorylation?

A
  • 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
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25
Q

What is the electron transport chain?

A
  • 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
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26
Q

How many protons does Complex 1 pump out?

A

4

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27
Q

How many protons does complex II pump out?

A

0

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28
Q

How many protons does Complex III pump out?

A

4

29
Q

How many protons does Complex IV pump out?

A

2

30
Q

What does gluco and glyco mean?

A

Sugar or glucose derivative.
Gluco - usually refers to the monosaccharide glucose.
Glyco - usually refers to the polysaccharide glycogen.

31
Q

What does neo mean?

A

new

32
Q

What does genesis mean?

A

formation of

33
Q

What does lysis mean?

A

to split or break apart

34
Q

What are the two main glucose anabolic processes?

A
  • Glycogenesis
    ▫ Formation of glycogen – polysaccharide
  • Gluconeogenesis
    ▫ Synthesis of new glucose molecules
35
Q

What is Glycogenesis?

A
  • 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
36
Q

What is Gluconeogenesis?

A
  • 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
37
Q

How are lipids stored?

A
  • in the form of triglycerides.
38
Q

What is lipolysis?

A
  • 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
39
Q

What is beta oxidation?

A
  • 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)
40
Q

What is a saturated fatty acid?

A
  • Saturated fatty acid
    ▫ Carbon chain is ‘saturated’ with hydrogen atoms
    ▫ All single covalent bonds
     No C-C double covalent bonds
41
Q

What is an unsaturated fatty acid?

A
  • Unsaturated fatty acid
    ▫ Carbon chain contains one or more double covalent bonds
    ▫ Monounsaturated – one double bond
    ▫ Polyunsaturated – two or more double bonds
42
Q

How many carbons are on a short chain fatty acid?

A

5 or less

43
Q

How many carbons are on a medium chain fatty acid?

A

6-12

44
Q

How many carbons are on a long chain fatty acid?

A

13-21

45
Q

How many carbons are on a very long chain fatty acid?

A

22 or more

46
Q

What is an omega fatty acid?

A

Omega refers to the end of
the carbon chain
▫ Methyl end (CH3)

47
Q

What does the number on the omega fatty acid indicate?

A
  • The number refers to the
    number of carbons from the
    omega end where the first
    double bond occurs
48
Q

What is lipid anabolism?

A
  • 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
49
Q

How are lipids transported?

A
  • 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
50
Q

How are proteins metabolised?

A

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

51
Q

How are proteins catabolised?

A
  • 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
52
Q

How does protein anabolism work?

A
  • 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
53
Q

What are the essential amino acids?

A
  • Tryptophan
  • Methionine
  • Valine
  • Threonine
  • Phenylalanine
  • Leucine
  • Isoleucine
  • Lysine
  • Histidine
54
Q

What are the non-essential amino acids?

A
  • Alanine
  • Arginine - possibly essential during infancy
  • Asparagine
  • Cysteine
  • Glutamic acid
  • Glutamine
  • Glycine
  • Proline
  • Serine
  • Tyrosine
55
Q

What is the human proteome?

A
  • 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.
56
Q

What is deamination?

A

Involves the removal of the amino group from the amino acid in
the liver or kidney

57
Q

What is Transamination?

A
  • 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
58
Q

How are metabolic reactions balanced?

A
  • 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
59
Q

Do oxidative and reduced states occur simultaneously?

A

-Known as REDOX cycle

60
Q

Extra facts about NAD and FAD

A
  • 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.
61
Q

What is the importance of oxidation?

A
  • 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
62
Q

What is the role of NADH in the electron transport chain?

A

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

63
Q

What is the role of FADH2 in the electron transport chain?

A
  • 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
64
Q

How is ATP produced?

A
  • 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
65
Q

Why is oxygen required?

A

The electrons re-enter the mitochondrial matrix
* Here, they bind with O2 and protons that have passed through
ATP synthase to form H2O

66
Q

What is the preferred energy substrate for the production of ATP?

A

Glucose

67
Q

How are lipids metabolised?

A
  • 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
68
Q

How are fatty acids catabolised?

A

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

69
Q

What are the types of fatty acids?

A
  • 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