TOPIC 2: FUNDAMENTAL CONCEPTS IN BIOCHEMISTRY Flashcards

1
Q

Cellular energy currency

A

ATP

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2
Q

General principles of metabolism

A
  1. Fuel molecules are degraded (catabolism) and large molecules made (anabolism) step-by-step in a series of linked reactions called metabolic pathways
  2. The energy currency of all life is ATP
  3. The oxidation of pre-existing carbon molecules drives the formation of ATP
  4. There are only a limited number of types of reactions in metabolism
  5. Metabolic pathways are tightly regulated
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3
Q

ATP consists of

A
  1. Adenine (N-containing base)
  2. Sugar (ribose)
  3. 3 phosphates
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4
Q

energy is released when

A

ΔG is negative

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5
Q

energy is captured when

A

ΔG is positive

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6
Q

ΔG < 0 (i.e. negative)

A
  • Energy is released (spontaneous, exergonic reaction)
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7
Q

ΔG > 0 (i.e. positive)

A
  • Energy input required (nonspontaneous, endergonic)
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8
Q

Electron carrier define

A

also called electron shuttles, are small organic molecules that play key roles in cellular respiration.

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9
Q

Redox reaction

A

involve oxidation (loss of electrons) or reduction (gain of electrons)
- Electron carriers (NADH and FADH2) perform this function, also called coenzymes (electron carriers)

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10
Q

structure of NAD

A

nicotinamide
ribose
adenine

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11
Q

structure of NADP

A

nicotinamide
ribose
adenine
extra phosphate

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12
Q

NADH is derived from

A

Niacin

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13
Q

niacin also called

A

nicotinic acid

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14
Q

nicotinic acid is converted to two very useful coenzymes

A

o Nicotinamide adenine dinucleotide (NAD)
o Nicotinamide adenine dinucleotide phosphate (NADP)

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15
Q

A molecule is oxidised when

A

it loses electrons

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16
Q

A molecule is reduced when

A

it gains electrons

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17
Q

NAD+ and NADP+ are the _______ forms

A

oxidised

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18
Q

NADH and NADPH are the ______ forms

A

reduced

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19
Q

6 classes of enzyme

A
  1. Oxidoreductases
  2. Transferases
  3. Hydrolases
  4. Lyases
  5. Isomerases
  6. Ligases
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20
Q

Oxidoreductases: type of reaction and an example

A

Oxidation-reduction
Lactate dehydrogenase

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21
Q

Transferases: type of reaction and an example

A

Group transfer
Nucleoside monophosphate kinase (NMP kinase)

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22
Q

Hydrolases: type of reaction and an example

A

Hydrolysis reactions (transfer of functional groups to water)
Chymotrypsin

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23
Q

Lyases: type of reaction and an example

A

Addition or removal of groups to form double bonds Fumarase

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24
Q

Isomerases: type of reaction and an example

A

Isomerisation (intramolecular group transfer)
Triose phosphate isomerase

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25
Q

Ligases: type of reaction and an example

A

Ligation of two substrates at the expense of ATP hydrolysis
Aminoacyl-tRNA synthetase

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26
Q

What kind of electron carriers are NAD and NADP

A

water soluble electron carriers

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27
Q

FAD

A

Riboflavin with an adenine mononucleotide attached

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28
Q

FMN

A

Riboflavin with a phosphate attached

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29
Q

Unlike NAD+ and NADP+, both coenzymes FAD and FMN accept

and therefore

A

2H+ and 2e-

As a substrate molecule undergoes oxidation, it releases 2 hydrogen atoms.

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30
Q

FAD and FMN also associate with

A

dehydrogenases, a type of oxidoreductase (class I)

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31
Q
  • Unlike NAD and NADP, FAD and FMN associate strongly with _______ there form a ________ group
A

enzymes and proteins
prosthetic group

32
Q

true or false FAD and FMN are water soluble electron carriers

A

false

33
Q

FAD and FMN function with

A

electron transport chains

34
Q

FAD and FMN derived from

A

ribflavin

35
Q

Concentration:

A

amount of solute dissolved in a known volume of solvent

36
Q

concentration equation

A

amount/ volume

37
Q

molarity equation

A

moles/ volume

38
Q

moles equation

A

mass/ molecular weight

39
Q

Communication is required to:

A
  1. Regulate development and organisation of cells into tissues
  2. Control growth and division
  3. Coordinate their diverse metabolic activities
40
Q

best known chemical signals are called

A

hormones

41
Q

hormones

A
  • Any substance in an organism that carries a signal to generate some sort of alteration at the cellular level
42
Q

hormones action in _____ is essential

A

homeostasis

43
Q

key characteristics of hormones

A
  • 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
44
Q
  • A huge number of different hormones have been identified on the basis of their chemical structure, there are three broad types
A
  1. Peptide hormones – e.g. prolactin, insulin, glucagon
  2. Steroid hormones – e.g. progesterone, testosterone, estradiol
  3. Amino acid derivatives – e.g. adrenaline, thyroxine, triiodothyronine
45
Q

growth factors

A

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

46
Q

All growth factors that have been isolated are

A

proteins – this is their difference from hormones

47
Q

hormones mechanism of action

A
  1. Effect on substrate concentration
  2. Effect on enzyme concentration
48
Q
  1. Effect on enzyme concentration
    a) Activation of pre-existing enzyme
A

 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)

49
Q
  1. Effect on enzyme concentration
    b) Increase in enzyme concentration by increased rate of synthesis
A

 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

50
Q

Target cells respond to a particular hormone or growth factor because they possess

A

specific receptor molecules

51
Q

These are specialized proteins capable of binding the hormone or growth factor with

A

high specificity and affinity

52
Q

Hormones are classified into two broad groups on the basis of their site of action:

A
  1. 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
  2. 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
53
Q

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

A
  • intracellular second messenger
    o This acts to notify the cell that the first messenger (hormone/ growth factor) has bound
54
Q

The first second messenger/ most important to be identified was

A

cyclic AMP

55
Q

Cyclic AMP-mediated response

A

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

56
Q

Steroid hormone receptors

A
  • 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
57
Q

hormone mechanism of action - if lipid soluble

A

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

58
Q

The endocrine system is controlled by the

A

hypothalamus and the hypophysis (pituitary gland) in the brain

59
Q

Blood glucose levels in the body are tightly regulated within a range of

A
  • 4 to 6 mM
60
Q

Regulation of blood glucose levels is achieved through hormones, primarily:

A

o Increase: glucagon
o Decrease: insulin

61
Q

Hyperglycemia

A

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

62
Q

Hypoglycemia

A

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

63
Q

Glucose

A
  • 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
64
Q

Insulin

A
  • 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
65
Q

Insulin has a plasma half-life of

A

only 6 min
o This allows rapid changes in circulating insulin levels
o Degraded by insulinase in the liver and kidneys

66
Q

Stimulation of insulin secretion

A
  • 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
67
Q

Inhibition of insulin secretion

A
  • 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
68
Q

insulin _mechanism of action

A
  • When insulin binds the alpha-subunits, tyosine kinase is activated and phosphorylates cellular proteins
69
Q

Insulin effect on metabolism

A
  1. Increases glucose uptake into muscle cells and adipocytes - ^GLUT4
  2. Increases glycolysis – because will use more glucose
  3. Decreases hepatic gluconeogenesis – because wont be producing glucose at a time we are trying to decrease it
  4. Increases glycogen synthesis, decreases glycogenolysis – so glucose isnt being released
  5. Increases triglyceride synthesis (in adipocytes) – so cells use glucose instead
  6. Decreases lipolysis
  7. Increases protein synthesis – so its not available as a feul source, same as trigs
  8. Decreases protein degradation
70
Q

Glucagon

A
  • 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
71
Q

Inhibition of glucagon secretion - Glucagon is inhibited by

A

elevated blood glucose

72
Q

glucagon_mechanism of action

A
  • 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
73
Q

Glucagon effects on metabolism

A
  1. Decreases glycolysis – want glucose in blood
  2. Increases hepatic gluconeogenesis – want increase glucose in liver
  3. Decreases glycogen synthesis, increases glycogenolysis (in liver not muscle) – don’t want to be packaging it away
  4. Decreases triacylglycerol synthesis – want to use this as a energy fuel instead of glucose, same for protein below
  5. Increases lipolysis (in adipose tissue)
  6. Decreases protein synthesis
  7. Increases protein degradation
74
Q

Insulin

A

↓ 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

75
Q

Glucagon

A

↑ 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