Metabolism Flashcards
1
Q
First Law of Thermodynamics
A
Total energy constant
Neither created/destroyed
2
Q
Anabolism
A
Cellular work
ATP -> ADP + Pi
3
Q
Catabolism
A
Energy from food
ADP + Pi -> ATP
4
Q
Eintake =
A
Eexpended + Estored
basal metabolism + activities) + (weight gain
5
Q
1J =
A
The energy to push 1N of force 1m
6
Q
Atwater factors Fat Carbohydrates Protein Ethanol
A
38
17
17
29
7
Q
Not all energy available eg
A
Cellulose - loss in faeces as fiber
Nitrogen - not oxidised and excreted in urine
8
Q
Direct calorimetry
A
Whole body calorimeters
Measure heat output
Good at measuring BMR
9
Q
Indirect calorimetry
A
O2 and CO2 using respirometer
1 mol O2 at STP = 22.4L
10
Q
Respiration exchange rate
A
CO2/O2
Determine if fuel used
11
Q
Basal metabolic rate
A
Energy expenditure at rest
Variation: gender, age, genetics, disease
12
Q
Increase BMR
A
Training Late pregnancy Fever Drugs (caffeine) Hyperthyroidism
13
Q
Decrease BMR
A
Malnutrition
Sleep
Drug (beta-blockers)
Hypothyroidism
14
Q
Process of digestion
A
1) Hydrolysis of bonds (b/e connecting monomer units)
2) Absorption of products
15
Q
Dietary carbonhydrates
A
40 - 50% energy intake
16
Q
Starch from plants
A
Amylose
Amylopectin
17
Q
Amylose
A
Linear polymer ⍺(1-4) linked glucose units
18
Q
Amylopectin
A
Branched polymer ⍺(1-4) & ⍺(1-6) linked units
19
Q
Cellobiose & lactose =
A
Stereoisomers
20
Q
Cellobiose
A
Repeating disaccharide unit in cellulose
Mammals don’t have enzyme to hydrolysed β(1-4) bond
21
Q
Maltase/isomaltase
Maltose/isomaltose ->
A
2 glucose
22
Q
Sucarse
Surcose ->
A
Fructose + glucose
23
Q
Lactase
Lactose ->
A
Galactose + glucose
24
Q
Starch digestion 1
A
Amylase hydrolyse ⍺(1-4) glycosidic bonds = small oligosaccharides
Producing maltose/isomaltose disaccharides
25
Starch digestion 2
At brush border
| Disaccharides -> monosaccharides
26
Digestion of protein
65g/day
| Source of nitrogen an essential animo acid
27
Deficiency of dietary protein
Kwashiorkor
| Osmotic imbalance in GI, retention of water
28
Protein digestion
Hydrolyses specific peptide bonds by several proteases
| 2 stages
29
All proteases
Secreted as inacitve forms
| Activated by cleavage of peptides from their structure
30
Proteases inactive form
Zymogens/ proenzymes
31
Specificity proteases
Adjacent a.a side chain
32
2 stages of protein digestion
Endopeptidases
| Exopeptidases
33
Endopeptidases
Attack peptide bond within protein polymer
| Pepsin, trysin, chymotrysin
34
Exopeptidases
Attack peptide bonds at the ends of protein polymer
Aminopeptidases = N - terminal
Carboxypeptidase = C - terminal
35
Zyomgen activation
Pepsinogen (zymogen) -> pepsin
HCL = parts of pepsinogen unfolds and activates peptin protease
= hyrolysis of pepsinogen = stably activated pepsin
36
Sequential hydrolysis of proteases
```
Peptin (stomach)
Trypsin (s.i)
Chymotrypsin (s.i)
Carboxypeptidase (s.i)
Aminopeptidases (s.i)
```
37
Bile salt function
Solubilize fats
| Forms micelles with TAGs (increase SA)
38
Bile salt structure
Hydrophoic and hydrophillic -ve surfaces
39
Bile salt produced and secreted regulation
Produced from cholesterol in liver and stored in gallbladder
| Secreted in response to cholecystokinin
40
Digestion of lipids
Pancreatic lipase/colipase enzyme + lipid/aqueous interface of micelles
= hydrolysis triacylglycerol at 1 & 3 of glycerol backbone
41
Digestion of lipids products
Smaller micelles (bile salt, free fatty acids, 2-monoacylglycerol)
42
Fat malabsorption
Excess fat and fat soluble vits in feces
Caused by interference with bile or pancreatic lipase secretion
eg xenical
43
4 classes of lipoprotein
Chylomicrons
VLDL ( carriers TAGs)
LDL (bad - collects on arteries)
HDL (good - absorbs cholesterol and carries to the liver)
44
Lipoprotein function
Solublise lipid to transport in blood to tissue
| Delivery system in/out cell
45
Apoprotein
ApoB
ApoE
ApoCII
46
ApoB
Structural for assembly
47
ApoE & B
Ligands for cell surface receptors
48
ApoCII
Enzymes cofactors
49
Lipid transport pathways
```
Exogenous chylomicron (dietary fat)
Endogenous VLDL/LDL (endogenously synthesised fats)
```
50
Chylomicron assembly
TAG & lipids + apoB (in ER) = chylomicrons
Secreted from intestinal epithelial cells to blood via lymphatic system
Milky after fat rich meal
51
Lipoprotein lipase
Enzyme on endothelial surface
ApoCII actives hydrolyse of TAG in lipoprotein = glycerol and fatty acids
Highest activity in heart & skeletal muscle
52
Defects in ApoCII or lipoprotein lipase
Increase chylomicrons and plasma triacylglycerol
53
Familial Hypercholesterolemia
Premature atherosclerosis (fat build up in arteries)]
Defect in LDL receptor gene
LDL x2-3 normal
54
Familial Hypercholesterolemia treatment
Statins (type of drug)
| Decrease LDL and increase HDL
55
Glucose transporters
SGLT1
GLUT2
Na+/K+ ATPase
56
SGLT1
Active
Against conc gradient
ATP needed
Glucose - Na+ symport
57
GLUT2
Facilitative
| Down conc gradient
58
Na+ outside cell
120-140 mmol/L
59
Na+ inside cell
20-30 mmol/L
60
Peptide absorption
Di- & tri- con-transported with H+
Membrane transporter PepT1
Further digested into a.a by cytoplasmic peptidase
61
A.a absorption
From lumen of s.i by transepitelial transport
62
A.a absorption
Semispecific Na+ - dependent transporter
63
Lactose intolerence
Lactose enzyme deficiency
| Fermentation of lactose by intestinal bacteria
64
Pancreatitis
Inappropriate activation of zyogens
| Self-digestion
65
Stomach ulcers
Breakdown mucosa
| No protection against protease action
66
Cystic fibrosis
Thick mucous secretions, block pancreatic duct & secretion pancreatic enzymes
Malabsorption
67
Coeliac disease
S.i
Reacts against gluten protein
Antibodies react with transglutaminase = villi flatten and no absorption
68
Nucleic acid polymers
Partically hydrolysed by acidic conditions
| Exonuclease enzymes release individual nucleotides
69
Vitamins characteristics
```
Essential
Organic molecules
No energy when broken down
Low = symptoms of deficiency
Small amounts required
```
70
Minerals characteristics
Essential
Non - organic elements
Low = symptoms of deficiency may appear
Small amounts
71
Bioavailability =
Amount absorbed/used
72
Accessing patients methods
Clinical Examination
Anthropometry
Biochemical tests
Dietary assessment
73
Dietary assessment
Measure what you eat
| Compare with Nutrient Reference Valves
74
Vitamins co enzymes
Organic carriers
| Make catalysis reaction smoother
75
Vitamins co factors
In catalysis - stablise adn help convert
Metabolism (energy)
Synthesis DNA/RNA
76
Minerals co factors
Transfer e- in redox
Structural role
Constituent of molecules
Nerve impulse, electrolyte balance
77
Niacin Deficient Diet
Vit B3
NAD & NADP
To carry redox = synthesis and breakdown carbs, lipids, a.a
78
Niacin Deficient Diet consequences
Low variety diet
4 D's
Rough skin, rash on areas exposed to sun
79
4 D's
Dermatitis (eczema)
Diarrhea
Dementia
Death
80
Mg2+ for muscle cramps
No solid evidence
81
ATP hydrolysis
-30kJ/mol
82
ATP synthesis
+30kJ/mol
83
Reaction coupling
G1 + G2 < 0
| Energetically favourable
84
Release of energy
Phosphorylation of ADP -> ATP
| Redox reaction
85
Oxidation
Energy release
Step - wise
Captures energy for ATP production
Without steps = energy released
86
Reduction
Coenzymes NAD & FAD
H -> H+ + e-
Enzyme > dehydrogenase
87
NAD
Carries 2e-, 1H+
| Glycolysis, fatty acid oxidation, CAC
88
FAD
Carries 2e-, 2H+
Fatty acid oxidation, CAC
Tightly bound to proteins which they interact with
89
CoA
Not carrier of e-
90
RBC glucose
Essential fuel
| Lack of mitochondria = no other pathway
91
Brain glucose
Favoured
Readily cross blood/brain barrier
120g per day
92
Eye glucose
Blood vessels & mitochondria refract light in optical path
93
White muscle cells glucose
Sprinting
Anaerobic
Fast twitch
94
Fatty acid preferred method
More reduced = more energy released
| Lower space needed for some amount of energy
95
TAG ->
Lipase
| FFA + glycerol
96
FFA transport into cell
In blood binds to albumin (albumin-FFA)
Passive into tissue and cell
In cell as FABP-FFA
97
FABP-FFA
FAtty acid binding protein
98
Glycerol transport into cell
Passive into liver
99
Beta-oxidation transportation
Outer
Fatty acyl-CoA carrier
Inner
Fatty acyl-carnitine
100
Beta-oxidation
Even no of carbons
Saturated
No ATP (energy transferred to NAD & FAD)
Cleavage b/w Calpha and Cbeta
101
Beta-oxidation products after 1 round
1 NADH
1 FADH
1 acetyl-CoA
eg C16 = 7 round (7 NADH, 7 FADH, 8 acetyl-CoA)
102
Isomerisation of citrate
Susceptible to decarboxylation
| Aconitase catalyse both steps
103
Synthesis of GTP
Energy eq of ATP
Energy from cleavage
P from soln
104
Citric Acid Cycle inhibited by
Fluoroacetate
105
Problem with fluoroacetate
Cannot undergo dehydration reaction
Inhibit pyruvate & build-up acetyl-CoA
= no metabolism
106
Deamination
Carbon skeleton
Free amino group
Cleavage by enzymes into soln
107
Carbon skeleton
Catabolic reactions
| Energy capture
108
Free amino group
Exerected
| NH4+
109
Transamination
Aminotransferase enzymes cataylse
Transfer amino group to keto acid <=>
P.P
110
P.P1
```
Pyridonal phosphate (without amino)
Co - enzyme
```
111
P.P2
Pyridoxamine phophate
112
Glucose - alanine cycle
Remove NH+ from muslce to liver and expelled as urea
113
Isolate mitochondria step 1
Tissue
Homogenisation in buffered surcose
Centrifuge at 1000xg
114
Stpe 1 products
Debris & nuclei
| Supernatant
115
Isolate mitochondria step 2
Supernatant
| Contrifuge at 7000xg
116
Spet 2 products
Pellet of mitchondria
Supernatant of membranes, ribosomes
and cytoplasm
117
Weak detergent on mitochondria
Only outer membrane removed
ETC works
No ATP synthesis
118
Strong detergent on mitochondria
Solubilises all membranes
| ETC doesn't work
119
ETC e- movement
```
Carrier accepts (reduced) or donates (oxidised)
To carrier with higher reduction potential
```
120
ETC energy usage
More protons across inner membrane
Increase intermembrane space
Decrease matrix
121
NADH pathway
1 - UQ - 3 - cyt c - 4 - O2
122
FADH pathway
2 - UQ - 3 - cyct c - 4 - O2
123
Inhibitors of ETC
Rotenone
Cyanide
Carbon monoxide
124
Rotenone
Inhibits transfer from 1 to CO-Q
125
Cyanide
Bind to carrier in 4
126
Carbon monoxide
Binds where O2 binds
127
Inhibitor consequences
Stops e- flow
Build-up reduced co-enzymes
No H+ gradient
Reactive oxygen species = damage to cells
128
UQ/COQ
2e- from 1/2
Moves within inner membrane
2 redox reactions (only accepts/donate 1e- at a time)
Q - cycles
129
Cytochrome C
Move on outer surface of inner membrane
1e- via reversible Fe2+/Fe3+ redox reaction
Heme containing protein
130
NADH no of protons
10
131
FADH no of protons
6
132
Experiments used to support chemiosmotic theory - ATP synthesis
Artifical liposome
| DNP
133
Artifical liposome
Bacteriorhodopsin - light inducible proton pump
In light = proton gradient
Yes ATP - light on
No ATP - light off
134
DNP
Uncoupler
Shuffle H+ from intermembrance space to matirx
Dissipate proton gradient
ETC continue, no ATP synthesis
135
Proton motive force
```
Chemical gradient/pH gradient due to H+ conc differences
Electrical gradient (+ve in intermembrane, -ve in matrix))
```
136
F1F0
Rotor subunits - turn
Stator subunits - doesn't turn
Proton flow drive rotor movement = conformational changes in stator
137
O =
T =
L =
Open - binding & releasing
Tight - ATP formation
Loose - hold ADP and P for catalysis
138
ATP from no of proton
4 protons = 1 ATP
139
Chemiosmotic coupling hypothesis knew
Inner membrane impermeable to protons and contains ETC
140
Chemiosmotic coupling hypothesis proposed
ETC pumps protons out of matrix
| pmf and that it drives ATP synthesis
141
GABA is a....
γ - aminobutyrate neurotransmitter transmitter
142
GABAa receptor
Membrane bound ligand - gated chloride channel
143
Increased NADH/NAD+ and ATP consequences
```
Slows:
CAC
ETC
Pyravate dehydrogenase
Glycolysis
Fatty acid oxidation
```
144
Fatty acid oxidation consequences
Fatty acid -> TAGs
| Fatty liver & hypertriglyceridemia (increase fatty acid in blood)
145
Increased NADH/NAD+ consequences
Pyruavate -> lactate (drives reaction)
= decrease pH
Inhibits gluconeogenesis (decrease blood glucose)
146
Alternative wat metabolisming alcohol
As toxin
| Microsomes ethanol oxidising system
147
Microsomes ethanol oxidising system disadvantages
Oxidase = extra e- on O2 = O2-
| Super oxidise = damges to tissue
148
Toxic effects from chronic alcohol consumption
```
Toxic acetaldehyde and reactive oxygen species
Fatty liver inflammation
Alcoholic hepatitis
Necrosis
Cirrhosis (death in liver cells)
Coma & death
```
149
Need for storing fuels
Body cannot store ATP (made when needed at rate needed by oxidising fuels)
Maintain glucose supply b/w meals
Immediate fuel from increase activity
Long periods without food intake
150
Fat storage
In adipose tissue
Triacylglycerols (TAGs)
Excess converted to TAGs
151
Fat synthesis
```
Fatty acids (from chylomicrons)
Glycerol backbone (from glucose)
Stimulated by insulin
```
152
Fat mobilisation
Hydrolysis of TAG
Catalysed by hormone sensitive lipase
Release of FFA and glycerol
153
Fat mobilisation hormones involved
Adrenaline and glucagon
154
Glycogen
Brushed polysaccharides
⍺ 1-4 & ⍺ 1-6 glycosidic bonds
Stored in liver and muscle
Granules in cytoplasm (stored until needed)
155
Glycogen synthesis
Occurs in liver and muscle after meal
ATP & UTP - energy inputs
Activated high - energy precursor, UDP - glucose
Insulin stimulated
156
Glycogen mobilisation
Degraded by glycogenolysis
Liver > released as glucose
Muscle > release fuel for glycolysis
Adrenaline binds to β adrenergic receptors on muslce cells
157
Excess glucose ->
Converted into fatty acid
| Exported as TAGs in VLDLto adipose tissue
158
Fuel for liver, heart
FFA
159
Fuel for muscle
Resting - FFA
| Marathon - FFA and glucose
160
Starvation survival
Supply brain with glucose (120g)
Supply other tissues with fatty acids
Conserve protein (maintain structure & function)
Hormone - glucagon
161
Lipolysis
Enough fuel for 40 days
| Use TAGs in adipose tissue
162
Glycerol movement after lipolysis
Into blood to liver
163
FFA movement after lipolysis
+ albumin in blood
| To all aerobic tissue except brain
164
Glycogenolysis
90 - 120g glycogen -> glucose
| Enough for brain for 1 day
165
Gluconeogenesis
In liver
| Energy provided by fatty acid oxidation
166
Gluconeogenesis synthesis of glucose
Lactate from muscle glycogen
Alanine from muslce protein
Glycerol from adipose tissue
167
Storage proteins
None
| Too much functional protein degraded into a.a = structural and functional damage = severe -ve N+ imbalance = death
168
Ketogenesis
Synthesised in liver from fatty acids
Can cross blood brain barrier
Reduce proteolysis by 1/2
Limited - make blood acidic so 7mmol = limit
169
Proteolysis
Breakdon of proteins & prevent -ve N+ imbalance
170
Ketone bodies levels
0mmol/L at start of fasting
171
ATP amount for how long
5micromol/g
| For 1 second
172
Phosphocreatine
20micronmol/g in muscle
| High-energy phosphate compound
173
Anaerobic glycoysis
ATP generate by substrate - level - phosphorylation
Rapid, short time only
Lactate = decrease pH in muscle = fatigue
174
Regulation in exercising muscle
Glycogen mobilisation - Ca2+ and adrenaline
Phosphofructokinase - increase by allosteric regulators
+ AMP & Pi
175
Use of ADP
ADP + ADP = ATP + AMP
| Adenylate kinase
176
Aerobic generation of ATP
Oxidation of glucose and fatty acids
| ETC, CAC, oxidative phosphorylation
177
Training consquences
Rely less on glycogen "top up"
| Muscles different with type of training
178
Marathon runner muscles
Type 1 fibres => red, slow - twitch
179
High jumpers muscles
Type 2 fibres => white, fast - twitch
180
Endurance type 1
Increase:
Capillaries, myoglobin content, no and size of mitochondria, capacity of mitochondria, oxidise lipid and carbohydrate capacity
181
Anaerobic
High intensity
Rapid generation of force
Short periods
182
Aerobic
Low intensity
| Prolonged, sustained force
183
% of anaerobic and aerobic depends on
Different durations involving maximal work
| Increase aerobic, increase exercise duration
184
Diabetes clinical symptoms
Fatigue
| Increas thirst and urination
185
Diabetes biochemical symptoms
Hyperglycaemia => constant high glucose
Glyucosuria => Overwhelm kidney's ability to filter glucose
Ketones
186
Insulin - dependent
```
Juvenile - onset
Type 1
Auto - immune destruction β cells
0.5% whole pop
Genetic and environment factors
Treatment - insulin injections
```
187
Non - insulin - dependent
```
Maturity - onset
Type 2
Resistance of insulin
2% whole pop
Genetic and environment factors
Treatment - diet, exercise, drugs
```
188
Long - term complication
```
Retinopathy
Neuropathy
Nephropathy
Cardiovascular disease
Peripheral vascular disease
```
189
Blood glucose high complications
Target structural proteins
| eg crystalline protein of eye, lens = opaque
190
Blood glucose low complications
<1mmolL-1
Sweating
Heartbeat increases
SNS = vomiting
No glucose for brain = convulsions, coma
191
Fluctuations glucose tolerence test
Increased plasma glucose vs normal and takes longer to decrease/ return to normal levels for diabetic
192
Fluctuations injected insulin
Mimic normal rise
| Abnormal decrease and takes longer to respond
193
Type 2 treatment
Hypoglycaemic drugs
| Impairs TAG usage - forcing glucose usage
194
Body Mass Index
= W/h^2
195
Obese
Overweight
Healthy weight
Underweight
>30
25 - 30
20 - 25
<20
196
Energy expenditure =
Basal metabolic rate
197
Basal metabolic rate depends on
Obligatory energy expenditure
Physical activity
Adaptive thermogenesis
198
Obligatory energy expenditure
Cellular and organ function
199
Adaptive thermogenesis
Variable, regulated by brain
Responds to temp and diet
In brown apipocyte mitochondria, skeletal muscle...
200
Increases risk of obesity =
Culture
Monogenic syndromes
Susceptibility genes
201
Brown fat
Special thermogenic tissue
Many mitochondria and fat droplets
Contains UCP
202
Uncoupling protein (UCP)
Inner mitochondria membrane
Regulate proton channels -> "couple" ATP synthesis by dissipating H+ gradient
Releases heat , increase metabolic rate, uses more fuels
203
White adipose tissue
UCP2, UCP3
| Increase metabolic rate and burn off excess energy
204
Lipin
Coded by obese gene
Hormoe from "fat" fat cells
Signals the brain to decrease food intake, increase energy expenditure
205
Lipin + ?
Lepun receptor in hypothalamus and other tissues
206
Strategies for treatment
BAT - oriented
Leptin/leptin - receptor
Anti obesity drugs
207
BAT - oriented
Stimulate existing BAT
Switch on brown fat differentiation and growth
Transplantation
208
Leptin
Mutant obese mouse doesn't produce leptin
Injected leptin = lipostat
Decrease appetite, increase energy use
209
Leptin - receptor
Obes diabetic mouse and fatty rat
Leptin receptor absent
2 - 6% severe obesity due to defect in MC4R in signalling pathway
210
Anti obesity drugs food breakdowwn
Xenical
| Pancreatic lipase blocked - less fat absorbed
211
Anti obesity drugs satiety signals
Trials underway
| Increase leptin levels
212
Anti obesity drugs mitochondria and brown fat
Future?
Uncouple oxidative phosphorylation from ETC
Increase functional BAT
213
White adipose tissue
Numberous hormones secreted for many pathways
| Multifunctional
