Metabolism Flashcards
1
Q
Draw a basic amino acid
A
Amino group, C, R group, H, Carboxyl group
2
Q
is there rotation around peptide bonds
A
No
3
Q
What are the bonding types in peptides
A
hydrogen, peptide, ionic, covalent/disulphide, hydrophobic, van der waals
4
Q
Why does ionic bonding in peptides arise
A
Electrostatic attraction between charged side chains
5
Q
Why does hydrogen bonding arise in peptides
A
Between C=O and N-H every 4 amino acids
6
Q
What are protein domains
A
further folding into a tertiary structure
7
Q
give the key features of an alpha helix
A
Stabilised by H bonds
Side chains project out
RH helices due to L-AA
Proline causes kinks due to no H bonds
8
Q
Give the key features of a beta pleated sheet
A
Stabilised by H bonds
C=O and N-H sticks out at right angles
Antiparallel strands
9
Q
What does warfarin do
A
Causes N-linked glycosilation where a sugar us added to asparagine to make glutamate so the correct conformation is adopted
10
Q
What are the non-polar amino acids
A
Glycine, Alanine, Proline, Valine
11
Q
What are the polar Amino acids
A
Cysteine (CH2-SH), Aspargine, Serine, Threonine, Tyrosine, Glutamine
12
Q
What are the hydrophilic side chain amino acids
A
Lysine (CH2)4-NH3 and Arginine (CH2)3-NH-C-(NH2)2
13
Q
What are the hydrophobic side chain amino acids
A
Aspartate CH3-CO2 and Glutamate (CH2)2- CO2
14
Q
Relate ATP to free energy
A
High energy anhydride bonds can be broken with energy (-31kJ/mol)
15
Q
How do lysozyme work
A
Hydrolyse a 1-4 glycosidic bond between NAG and NAM
16
Q
What amino acids do lysozyme require
A
Aspartic and glutamic acid
17
Q
What is the optimum pH for lysozyme
A
5.0 as aspartic acid is deprotonated by glutamic acid is not
18
Q
Describe/draw the process of lysozyme action
A
diagram
19
Q
Give the three overall steps of metabolism
A
Digestion - enzymes break down larger molecule to smaller ones
Cellular metabolism I - Oxidation of molecules in the cytosol
Cellular metabolism II - oxidation of molecules generated from CM1 within the mitochondria
20
Q
Give the process of glycolysis, including enzymes
A
10 step process
21
Q
What are the three fates of pyruvate
A
Alcoholic fermentation
Lactate generation
Link reaction
22
Q
Describe alcoholic fermentation
A
Pyruvate is converted to acetaldehyde using pyruvate decarboxylase (-CO2). Then conversion to ethanol using alcohol dehydrogenase
23
Q
Describe lactate generation
A
Pyruvate is converted to lactate using lactate dehydrogenase
24
Q
What happens to lactate produced
A
Travels to the liver where it is used to generated pyruvate
25
When will lactate dehydrogenase levels be elevated
Stroke, heart attack, muscle injury
26
Describe the link reaction
Pyruvate is converted into acetyl coA using pyruvate dehydrogenase
27
Describe the pyruvate dehydrogenase complex
```
5 co factors and 3 enzymes.
Pyruvate decarboxylase + TPP
Lipoamide reductase transacetylase + lipoamide
Dihydroxylipoyl dehydrogenase + FAD
NAD + CoA
```
28
describe the pyruvate dehydrogenase complex mechanism
Decarboxylation to produce hydroxyethyl TPP
Oxidation and transfers to lipoamide (swinging arm) to produce acetyl lipoamide
Transfer of acetyl to acetyl coA
Regeneration of oxidised lipoamide and FAD, producing NADH
29
What does TPP deficiency lead to
Beri-Beri
30
What is Beri-Beri caused by
TPP deficiency
31
Compare ATP production by aerobic and anaerobic respiration
38 vs 4
32
How can glucose respiration be used for cancer
Tumour cells use a lot of glucose so using radioactively labelled glucose which emits positrons, a PET scan will detect the locations of tumours
33
Where are the TCA enzymes located
Mitochondrial matrix, except succinate dehydrogenase which is on the inner membrane and coupled to ubiquinone
34
What does one turn of the TCA cycle produce
2 CO2
3 NADH
1 FADH2
1 GTP
35
Describe the TCA cycle
process
36
Describe transamination
Transfer of the amine group from an amino acid to a keto acid. Enzyme example = alanine by alanine aminotransferase
37
What are the two ways NADH is "transported" to the mitochondrial matrix
Glycerol phosphate shuttle
| Malate aspartate shuttle
38
Where is the glycerol phosphate shuttle used
Brain, skeletal muscle
39
Describe the glycerol phosphate shuttle
glycerol-3 phosphate dehydrogenase transfers electrons to glycerol-3-phosphate which transfers the electrons to FAD, which then passes to co-enzyme Q in the ETC
40
Where is the malate aspartate shuttle used
Liver, kidney, heart
41
Describe malate aspartate shuttle
diagram
42
Compare anabolic and catabolic
NADPH to create molecules vs NADH used to break down molecules
43
What is NADPH used in
Anabolic reactions
Thymidine synthesis (DNA)
Cholesterol synthesis catalysis
44
How is cancer related to metabolism
Cancer cells rely on anaerobic respiration when there is reduced TCA activity and so even in high O2 concentration anaerobic respiration occurs (warburg)
45
What is the evidence for the evolution of mitochondria
```
can only form from existing mitochondria
circular genome
Own protein-assembly machinery
Antibiotics that affect bacterial transcription affects the mitochondria e.g. streptomycin
First amino acid of transcripts is fMet
```
46
What is chemiosmotic theory
Protons are translocated to the intermembrane space where an electrical potential and pH gradient forms. protons can move back to the matrix through an ATP synthase channel
47
What are the three inner membrane complexes
NADH dehydrogenase complex
Cytochrome B complex
Cytochrome Oxidase complex
48
What are the protein transporters
Ubiquinone and cytochrome C
49
Where do NADH and FADH2 feed their proteins into
NADH feeds into NADH dehydrogenase complex = 3ATP
| FADH2 feeds into ubiquinone = 2ATP
50
describe ATP synthase
ATP synthase is a multimeric enzyme that consists of F0 and F1. Protons passing through causes rotation which gives transition states with altering affinities for ATP and ADP. Generation or consuming of ATP depends on direction of proton flow
51
What does the F0 unit contain
a,b,c units
52
What does the F1 unit contain
alpha, beta and gamma
53
Describe the process of ATP synthesis in oxidative phosphorylation
1. proton flow
2. c subunit (attached to gamma subunit) rotates
3. alpha and beta remain stationary, being fixed by b
4. movement causes ATP generation
54
What is the effect of cyanide
binds to Fe3+ in cytochrome oxidase, blocking electron flow
55
What is the effect of malonate
Competitive inhibitor of succinate dehydrogenase, slowing flow of electrons to ubiquinone
56
What is the effect of oligomycin
Inhibits oxidative phosphorylation by binding to the ATP stalk and blocking it
57
What is the effect of DNP
proton ionophore that can shuttle protons. DNP uncouples oxidative phosphorylation from ATP production, Increase in temp. and metabolic rate as heat is released from the ETC.
58
What can acetyl coA be used for
TCA cycle
Sterols and fatty acid production
Ketone bodies
Protein acetylation
59
Difference between saturated and unsaturated fatty acid
unsaturated = double bonds
60
What is the structure of a triglyceride
1 glycerol and 3 fatty acid chains held by ester bonds
61
Where are fatty acids stored
Stored as triglycerides in adipocytes
62
How much ATP does fat produce
129 ATP
63
What are the 4 basic steps of lipid metabolism
Conversion to acyl coA
Transport to the matrix
Beta oxidation
Acetyl coA production
64
How is acyl coA produced
using Acyl coA synthesise and hydrolysing TWO anhydride bonds from ATP to produce AMP
65
How is acyl coA transported to the matrix
Using the carnitine shuttle;e
Acyl is transferred to carnitine by carnitine acyltransferase I
Acyl carnitine is transported through translocate
Reverse occurs in the matrix
66
Describe beta oxidation
4 steps: oxidation, hydration, oxidation, thiolysis
acyl coA dehydrogenase forms 3 hydroxyacyl and FADH2
3-hydroxyacyl hydrolase forms L-3hydroxyacyl coA
L-3hydroxyacyl coA dehydrogenase and NADH
beta ketothiolase splits into acyl coA (-2C) and acetyl coA
67
How do you work out how many cycles were needed
/2 then -1
68
How many carbons in palmitoyl coA
16
69
What is required for acetyl coA to enter
balance of beta oxidation and carbohydrate metabolism to produce oxaloacetate
70
What occurs if fat metabolism is greater than carb metabolism
Ketone body formation
71
When does ketone body formation occur
When fat metabolism is greater than carb metabolism and during fasting
72
Describe the formation of ketone bodies
Acetyl coA forms acetoacetyl coA
formation of 3-hydroxy-3methyl glut aryl coA (HMG coA)
formation of acetoacolate
D-3 hydroxybutyrate and acetone
73
What is the basic mechanism of fatty acid synthesis
Decarboxylative condensation
Reduction
Dehydration
Reduction
74
Describe decarboxylative condensation
Make a malonyl coA from acetyl coA to donate carbons using acetyl coA carboxylase and ATP
binding of malonyl coA to ACP
binding of acetyl coA to ACP
Condensation of Acetyl and malonyl coA to produce acetoacyl coA and releasing CO2
75
What is ACP
Acyl carrier protein that acts as a swing
76
After decarboxylative condensation what occurs in fatty acid synthesis
Reduction of acetyl coA using NADPH
Dehydration
Reduction using NADPH
After many repeats, hydrolysis of ACP
77
Which enzymes catalyses fatty acid synthesis
acetyl coA carboxylase and fatty acid synthetase
78
Compare fatty acid metabolism to synthesis
coA vs ACP
FAD/NADH vs NADPH
Matrix vs cytoplasm
79
What is MCAD
Medium chain acetyl coA dehydrogenase deficiency
Autosomal recessive disease where one cannot burn fat
Cannot fast and lots of glucose must be taken
Causes SIDS
Detected via heel prick
80
What is primary carnitine deficiency
Autosomal recessive disease
Unable to shuttle acyl coA
mutation in the gene that tajes up carnitine
Supplement given (carnitor)
81
How many carbons is cholesterol
27C
82
What is the overall mechanism for cholesterol synthesis
Make IPP
Condense 6 IPPs
Modification of squalene
83
How is IPP made
Combine two acetyl coA to form acetoacetyl coA using beta ketothiolase
Add another acetyl coA to form HMG-coA using HMG-coA synthase
Reduction to form mevalonate using HMG-coA reductase
Sequential phosphorylation and decarboxylation
84
What is IPP
Isopentyl pyrophosphate
85
What does statins target
Formation of cholesterol by targeting the formation of mevalonate using HMG-coA reductase
86
How is IPP combined
IPP and an isomeric form is combined to produce geranyl pyrophosphate (10C) which then forms farnesyl PP (15C).
2 of farnesyl PP are combined to form squalene (30c)
87
Describe cyclization
Squalene is converted to lanosterol using cyclase
| Lanosterol forms cholesterol (27C) in 19 steps and demethylation
88
What do all 5 steroid hormones derive from
Pregnenolone
89
What does cholesterol break down into
Glycocholate
| Taurocholate
90
What are the key features of bile salts
Bile salts are synthesised in the liver and stored int he gall bladder. It is needed for fat and fat soluble vitamin digestion. It is released into the small intestine to emulsify fats
91
Summarise vitamin D production
Melanocytes in the skin
| 7-dehydrocholesterol conversion to pre vitamin D after exposure to UV light. Conversion to vitamin D and calcitrol.
92
What does vitamin D deficiency lead to
Ricketts
93
What is the role of lipid rafts
In the plasma membrane and they assist in movement of cell surface receptors
94
Describe the process of lipid absorption
TAGs broken down into MAGs or DAGs and fatty acids by lipase
Emulsification by bile salts and cholesterol to form a mixed micelle
Mixed micelles past through the gut lining via enterocytes
MAGs and fatty acids reform TAGs
TAGs incorporated into a chylomicron with cholesterol and apoproteins
Drainage into the lymphatic system via a lacteal
95
What is the structure of a chylomicron
TAG and cholesterol ester core
| Surrounded by free cholesterol, phospholipid and apoproteins
96
Where is lipoprotein lipase located and what is its function
Located on capillary endothelial cells in adipose and heavy skeletal muscle. in breaks down TAGs into glycerol and fatty acids
97
What happens to the leftover chylomicron after breaking down by lipoprotein lipase
The rest travels to the liver where it forms lipoprotein: cholesterol, low density lipoproteins, high density lipoproteins
98
Compare low density and high density lipoproteins
Low density = takes cholesterol from the liver and delivers to peripheral tissue leading to athersclerosis
High density = takes cholesterol from peripheral tissue to the liver
99
What is familial hypercholesterolaemia
Receptor mediated endocytosis by LDL receptor in the liver usually. Mutant LDL receptor means the LDL is left in circulation.
Dominant condition
Leads to athersclerosis and heart attacks
Most cases are not from mutation, but from obesity, alcohol, diet and diabetes
100
What is the treatment of hypercholesterolaemia
Statins which inhibit HMG-coA reductase
| Resins which inhibit absorption of bile salts and cholesterol
