Biological Molecules, Enzymes And Metabolic Pathways Flashcards
Classes of nutrients (8)
- carbohydrates
- lipids
- water
- minerals
- protein
- vitamins
- DEBATED: alcohol or finer
Examples of complex chemical structures
- vitamins
- carbohydrates
- proteins
- lipids
- alcohol/fiber
Examples of simple chemical structures
- water
- minerals
Vitamin B12 structure, role in the body
- has a corrin ring, with Cobolt in the Center
- cobolt is bound to 4 nitrogens, meaning wealth of electrons and ability to be bioactive
- cofactor for isomerases (breaking c-c bond) and methyltransferases
- spirulina contains different structure and is referred to as pseudo vitamin b12. Does not behave as a cofactor
Stereoisomers: what are they in the context of amino acids?
- mirror images
- D enantiomer: the right configuration
- L: left configuration, generally preferred by the body
- amino acids can form enantiomers around the chiral carbon (except glycine)
Non- Polar amino acids
Glycine, alanine, cysteine, valine, proline, leucine, isoleucine, methionine, tryptophan, phenylalanine
Polar amino acids
Serine, threonine, tyrosine, asparagine, glutamine
Positively charged (basic) amino acids
Lysine, arginine, histidine
Negatively charged amino acids
Aspartic acid, glutamic acid
Protein secondary structure
- alpha helix: non- polar amino acid R groups in Center (hydrophobic)
- beta pleated sheet: hydrogen bonds form across plane
Largely determined by R group
Protein tertiary structure
3D structure determined by VDWF, hydrogen bonds, disulphide bridges
Example: collagen, lots of proline introduces kinks in chain, tightly wound structure
Definition of an isotope
Electrons and protons are the same, differing number of neutrons, which give a different atomic mass
There are intrinsically stable isotopes (safe for use in humans, such as C13), and radioactive isotopes
Mass spectrometer steps
1) vaporised substance is ionised (charged) at the inlet
2) voltage pushes down the tube
3) electromagnet deflects the particle
4) particle detected at detector
Strength of electromagnet determines deflection and can be used in deciphering peaks (M+ peak as reference)
Quadrupole mass spectrometer
- can be coupled with gas chromatogram
1) ions added into source
2) voltage pushes through
3) the 4 quadrupole rods determine polarity; frequency of polarity changed
4) some ions will reach resonance at particular polarity switching frequency and will fly down tube like a corkscrew
5) detected
Principle of isotope tracer (decay and infusion experiments)
- bath example
- if you know how much isotope you are putting in, and how much is coming out you can work out the rate of reaction (protein turnover)
- the size of the pool
Definition of half life
T 1/2: Time taken for half of a molecule to be replaced
Usually expressed in days
Ornithine decarboxylase is a fast example- ~20 mins in response to skin burning. For polyamine synthesis (molecular grease)
Conversion between half life and fractional rate:
T1/2: log2 (0.693)/fractional rate
Definition of fractional rate
Ks or Kd = The fractional amount replaced per unit time (expressed as d-1)
Example:
0.1 d-1 is 10% replaced per day
Ks or Kd: log2 (0.693)/t1/2
Amino acid supply and ribosome turnover
Example from Clifford (1972)
Cells have constant amino acid demand
Shown in experiment that when in amino acid starved medium, ribosomes and mRNA were broken down to give back to the amino acid pool
Essential amino acids
Protein with essential amino acids is referred to as having a ‘high biological value’; those lacking in one or more are said to have a ‘low biological value’
Histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine
Non- essential amino acids
Have wealth in body and can create own
Alanine, aspartate, glutamate, cysteine, tyrosine
Conditionally essential amino acids
These are amino acids which may become essential under certain conditions
Arginine (essential in pre-term infant), asparagine, glutamine (trauma and cancer), glycine, proline, serine
Carbohydrates
Stimulate insulin secretion
In a fed state, will oxidise glucose for energy
In a faster state, without carbohydrate, will oxidise fat for energy
Types of starch (polymer of D-glucose)
Rapidly digestible (RDS): readily available for pancreatic amylase, digested quickly in small intestine (eg. Freshly cooked starch foods)
Slowly digestible (SDS): slow and complete digestion in small intestine (eg raw cereals)
Resistant starch (RS):
- physically inaccessible eg. Partly milled grains/seeds
- resistant granules eg. Raw potato, green banana
- retrograded amylose eg. Starch that has been cooked and cooled
Glycemic Index (GI)
GI= (area under test food glycemic curve/ area under reference glycemic curve eg. Glucose) x 100
Low GI <40
Medium GI 41-70
High GI >70
(Can later GI by eaten foods which have cooled; reterograded amylose; less available for digestion in small intestine)
Glycemic load
The amount of starch eaten, total
Lipid definition
Groups of compounds that do not readily dissolve in water
Includes: fatty acids, triglyceride, phospholipids
Definitions of saturated/ monounsaturated and polyunsaturated fats
Saturated: no double bond (C18:0) eg. Stearic acid
Monounsaturated: one double bond eg. Oleic acid, 75% constituent of olive oil (C18: 1)
Polyunsaturated: more than one double bond eg. Linoleic or alpha-linoleic acid 18:2n-6 (omega 6), 18:2n-3
Naming system describes number of C on chain: number of c=c(n) - position of double bond on chain (eg. On carbon 3)
Mechanism of fat storage
- Insulin secreted when blood glucose is high
- this stimulates uptake of lipoprotein particles from the liver (VLDL) into adipose tissue; glucose is also being taken in via GLUT4 and engages in lipogenesis
- lipoprotein lipase (LPL) then breaks down into fatty acids which are esterified to triglycerides
Mechanism of fat mobilisation
- during fasting/starvation, hormone-sensitive lipase (HSL) breaks down triglycerides in adipocytes
- this mechanism is stimulated by adrenaline, noradrenaline and possibly glucagon (insulin antagonises this step)
- fatty acids and glycerol leave adipocytes and fatty acids (palmitate) are bound to albumin and transported to periphery (liver) where enter beta-oxidation cycle-> acetyl CoA -> Krebs cycle -> CO2
Metabolism of polyunsaturated fats (omega 6 example)
1) desaturated (via desaturase). delta 6 desaturase: 18:2n-6 -> 18:3n-6
2) elongated (via elongase): 18:3n-6 -> 20:3n-6
3) desaturated again (via desaturase). Delta 6 desaturase: 20:3n-6 -> 20:4n-6 = arachidonic acid
Conversion of omega 3 (18:2n-3) to EPA in humans
- experiment using isotopic labelling (C13), where participants were fed labelled omega 3, and CO2 in breath (palmitate-> beta oxidation -> acetyl coa-> Krebs cycle-> CO2) was measured as a sign of fatty acid oxidation (along with periodic blood tests)
- found that women were more effective than men at converting to EPA (~15% converted vs 2-3%)
- explains why we have gender differences in recommendations
Eicosanoids
- produced from oxidation of PUFA and oxidation or arachidonic acid (from metabolism of omega 6)
- has a role in inflammation, immunity, blood pressure and clotting
Ways of producing ATP
- glycolysis
- creatinine phosphate
- TCA cycle
- amino acid oxidation
- Acetyl CoA (first substrate of the TCA cycle)
- amino acid oxidation
- ketone oxidation
- glycolysis
- beta- oxidation of fatty acids
Definition of redox reactions (NAD+ example)
Reduction, oxidation reaction
(Loss of electrons= oxidation, gain electrons= rescued)
NAD+ is a high energy intermediate (coenzyme) which aids in redox reactions
Types of enzyme and what they do (oxidoreductase, transferases, hydrolases, lyases, isomerases, ligases)
- oxidoreductases: transfer of electrons
- transferases: group transfer reaction
- hydrolases: hydrolysis reaction (transfer of functional groups to water)
- lyases: addition of groups to double bonds or formation of double bonds by removal of groups
- isomerases: transfer of groups within molecules to yield isomeric forms
- ligases: formation of c-c, c-s, c-o and c-n bonds via condensation reactions coupled to atp cleavage
How enzymes overcome energy barriers for reactions
- enzymes reduce the activation energy (free energy, G0) needed for a chemical reaction
- forms a transition state with substrate, and a series of intermediates formed with lower energy requirements, so the deltaG is lower
Mineral cofactor examples
- Fe2 or 3+: cytochrome oxidase, catalase, peroxidase. Ferrous and ferric forms allow for series of redox reactions to occur
- FeMo: denitrogenase, donates a series of electrons to progressively reduce nitrogen until protons donated
Coenzyme examples and dietary sources
- biocytin : transfers CO2, found in biotin
- coenzyme b12: transfers H and alkyl groups, found in b12
- NAD: transfers hydrides, found in niacin