Metabolism Flashcards
(462 cards)
1
Q
How is energy conserved primarily
A
In the form of ATP
2
Q
Generally catabolic pathways are what and do what?
A
Oxidative, release free energy and produce intermediates
3
Q
Generally anabolic pathways are what?and do what
A
Reductive, use intermediates and energy in synthesis
4
Q
ADP+Pi, to become ATP what is generally needed and what are the byproducts
A
Oxygen added, CO2 H2O and heat biproducts
5
Q
What are NAD+, FAD and NADP+ examples of?
A
Carriers of reducing power
6
Q
What is the purpose of carriers of reducing power?
A
When a substrate is oxidised these are reduced, storing the energy of the bond
7
Q
What concentration should carrier of reducing power be kept at in a cell
A
Needs to be a constant concentration
8
Q
How are carriers of reducing power kept at a constant concentration?
A
Reoxidation reactions:
Cell respiration
Reactions where the substrate is reduced
9
Q
What is a key example of carriers of reducing powers being kept at a constant concentration when oxygen isn’t available for cell respiration
A
Pyruvate +NADH+H+-> Lactic acid + NAD+
10
Q
What are some examples of reduced carrier states
A
NADH + H+
NADPH + H+
FAD2H
11
Q
NAD+, NADP+ and FAD are all examples of what? What do they need to be synthesised in the body?
A
Oxidised carriers
Nicotinamide from niacin
Flavin from vitamins
12
Q
What needs a constant supply of glucose
A
Brain and RBC
13
Q
How else can glucose be obtained other than diet
A
Gluconeogensis of amino acids, glycerol, dietary sugars
Glyconeolysis
14
Q
What are dietary fat soluble vitamins
A
D E A K
15
Q
What essential fatty acids are part if the cell membrane component
A
Linoleic and linolenic
16
Q
How is glucose released from dietary polysacharides like starch and glycogen
A
Glycosidase enzymes
17
Q
What are dietary polysacharides broken down into?
A
Glucose, maltose, dextrins
18
Q
Where does the digestion of polysacharides begin?
A
In the most with salivary amylase
19
Q
After partial digestion of dietary polysacharides in the mouth, what happens in the jejunum
A
Pancreatic amylase continues to break down to maltose, lactose, sucrose, dextrins, glucose
20
Q
Where does the digestion of maltose, lactose, sucrose occur
A
Brush border of epithelial cells in jejunum and duodenum
21
Q
What enzymes release glucose, fructose and galactose from the partially broken down polysacharides in the gut
A
Lactase, sucrase, isomaltase, glycoamylase.
22
Q
Who’s lactase activity is high?
A
Babies/infants
23
Q
Where are polypeptides initially broken down
A
Stomach, pepsin breaking peptide bonds
24
Q
Once peptide bonds of polypeptides have been broken in the stomach, what continues the breakdown in the small intestine
A
Trypsin, chymotripsin, carboxypeptidase
25
What are the 9 essential amino acids+ mnemonic
If learned this huge list may prove truly valuable
| Isoleucine, leucine, threonine, histidine, lysine, methionine, phenylalanine, tryptophan, valine
26
What 3 additional amino acids to the essential amino acids, can become essential in pregnancy and childhood?
And Then Children
| Arginine, Tyrosine, Cysteine
27
Where is fat broken down initially, and by what?
Small intestine by pancreatic lipase
28
What is the purpose of bile salts in relation to fat
Emulsifies the fat, making it small enough for pancreatic lipase to break it down
29
What are fats broken down to so that they can be absorbed
Free fatty acids and monoglycerides
30
What happens to the monoglycerides and free fatty acids once entering gut epithelial cells?
In the ER they are resynthesised to TAGs. Coated in protein to form chylomicrons. Enter lymphatic capillaries (lacteals), then entering blood via thoracic duct
31
Where do the chylomicrons drain into from the gut
Left subclavian vein from the thoracic duct
32
What is the first reaction in glycolysis
Glucose +ATP -> glucose-6-phosphate +ADP
33
What enzymes are needed for the first step of glycolysis
Glucokinase in liver and pancreas
| Hexokinase in other cells
34
What is the first step in glucose metabolism an example of
Phosphorylation
35
What is the purpose of the first step of glycolysis
Makes sugar anion (prevents leaving plasma membrane)
Increase sugar reactivity
Allows for substrate level phosphorylation
36
What is difference about glucokinase to hexokinase
Glucokinase only works at high glucose concentrations
37
What is dietary lactose broken down into
Glucose and galactose
38
What is the time line of conversions from galactose to glucose 6 phosphate
Galactose -> galactose 1-P -> glucose 1-P -> G6P
39
What is required in the first step of galactose metabolism
Galactokinase enzyme
| ATP
40
What enzyme is required for the forward reaction from galactose 1P to glucose 1P
What enzyme is required for the reverse reaction and why is the reverse reaction important
Galactose 1-P uridyl transferase (forward)
| UDP-galactose 4 epimerase, important in breast feeding
41
What does accumulation of galactose result in
Galactitol
42
How is galactitol produced
In galactose excess, Aldose reductase (req NADPH)
43
What happens if the production of Galactitol is favoured in galactose excess
Depletes NADPH-> cataracts
| Increases ocular pressure-> glaucoma
44
What enzyme is commonly absent in galactossaemia
Galactose 1-p uridyl transferase
45
An absence of galactose 1-P uridyl transferase results in what
Accumulation of galactose 1-P and galactose (that's converted to Galactitol)
46
Why is accumulation of galactose 1-P dangerous?
It sequesters Pi, damages liver kidney and brain
47
What is dietary sucrose converted into
Glucose, fructose
48
Where is fructose converted and what is it converted to, to enter glycolysis
Glyceraldehyde 3 phosphate in the liver
49
What is the first unique reaction to glycolyis
Conversion of fructose 6 phosphate to fructose 1-6 bis phosphate
50
What is the second step of glycolysis. Reversible or irreversible ?
G6P -> F6P reversible
51
What is the 3rd step of glycolysis?
What enzyme?
What's special about this step?
F6P-> Fructose 1,6,bisphosphate
PFK
Committing step of glycolysis
52
Why is the conversion to F1,6BP with catalyst PFK the 'commiting step'
It's irreversible with a large negative value (energy)
53
What size carbon ring is F1,6,BP?
6 carbon
54
Step 4 and 5 of glycolysis represents what (in relation to structure)
Starting compound is F1,6,BP
Cleave from 6 carbon to 2 3 carbon molecules that are interconvertible
Dihydroxyacetone-P and Glyceraldehyde 3-P
55
What is important about the 3 carbon intermediate produces from step 4 in the glycolysis pathway what're F1,6,BP has been cleaved to form dihydroxyacetone-P and glyceraldehyde 3-P
Dihydroxyacetone-P needed to make glycerol phosphate
56
In step 6 of glycolysis, what is glyceraldehyde converted into?
What does it reduce?
What's important about its converted molecule?
1-3- bisphosphoglycerate
NAD->NADH
1-3 bisphosphoglycerate goes on to form 2,3 BPG for o2 affinity
57
Reaction 7 of glycolysis with 1-3 bisphosphoglycerate.
What's the end product
What is produced
What is this an example of
3 phosphoglycerate
ATP
Substrate level phosphorylation
58
What is step 10 of glycolysis
What's the end product
Why is it irreversible
What's it an example of
Phospheonolpyruvate -> pyruvate
Large energy change
Substrate level phosphorylation
ATP produced
59
What are 4 key points about the first 10 steps of glycolysis
No co2 lost
2 atp required, 4 produced
Glucose oxidise to pyruvate
Some C3 intermediates made that are needed for other things
60
What's the most important rate limiting step in glycloysis phase 1/2
Step 3 with PFK
61
How is glycolysis regulated
High energy signalling and hormonal control
62
How is PFK regulated
Allosterically but ATP/ADP
Insulin stimulates
Glucagon inhibits
63
In low oxygen circumstances what is pyruvate converted to? What's required
Lactate
| NADH
64
Under normal physiological conditions how much lactate is produced in a day?
Where from mainly?
50g
| RBC, brain, Skin, Lungs, GI
65
If rate of lactate production is equal to utilisation, what is blood lactate
<1mmol/L
66
Where is blood lactate processed
Liver, kidney and heart
67
How is lactate processed in the heart?
Converted to pyruvate with LDH
| Oxidation into energy
68
How is lactate processed in the liver and kidney
Converted to pyruvate with LDH
| Then either enters TCA cycle or undergoes gluconeogensis
69
When is lactate 'above the renal threshold'
5mmol and up
70
What are the 2 overarching causes of increased blood lactate
Increased production or decreased utilisation
71
What can increase the production of lactate
Exercise
Big meal
Shock
Congestive heart disease
72
What can decrease the utilisation of lactate
Liver disease
Thiamine defficency
Alcohol metabolism
73
How does the body have a constant supply of glucose between meals?
Glycogen stores
74
How is glycogen described
A highly branches polymer of glucose
75
What bonds does glycogen have at branch points?
Alpha 1,6
76
What bonds does glycogen have, not at the brach points
Alpha 1,4 glycosidic
77
Where is glycogen stored
Granules in liver and skeletal muscles
78
Where is the highest amount (g) of glycogen stored?
Skeletal muscles 300g
79
What limits the amount of glycogen that can be stored
It's very polar
80
What are the 2 enzymes involved in addidng further glucose to glycogen
Glycogen synthase and branching enzyme
81
What's the ratio of glycosidic bonds to branch points in glycogen
10:1
82
In glycogenesis what is G6P initially converted to and with what enzyme?
Reversible or not?
G1p with phosphoglucomutase
| Reversible
83
In glycogenesis how is G1P altered to eventually join glycogen?
UTP+ H20 added creating UDP glucose +2Pi
| UDP glucose added to glycogen, losing UDP in the process
84
What promotes the formation of glycogen and what inhibits it
| ?
Insulin promotes it
| Adrenaline and glucagon inhibit it
85
When is glyconeolysis initiated?
In response to exercise in skeletal muscle
| In response to fasting in the liver
86
What enzymes are active in glyconeolysis and what do they catalyse?
Glycogen phosphorylase acts on alpha 1,4 bonds
| De-branching enzyme acts on alpha 1,6
87
What can muscle stores not make from glucose 1 p in glyconeolysis?
Glucose due to lack of glucose 6 phosphotase
88
Where is glucose 6 phosphotase and what is its purpose
In the liver and can convert G6P to glucose to be mobilised into the blood
89
What is glucagon action on glycogen synthase
Decrease
90
What is insulins action on glycogen synthase
Increase
91
What is glucagon action on glycogen phosphorylase
Increase
92
What is insulins action on glycogen phosphorylase
Decrease
93
Where is the pentose phosphate pathway very important
Liver
RBC
Adipose
Dividing tissues
94
Why is the pentose phosphate pathway important
Produces NADPH for anabolic processes
| Produces C5 sugar ribose for nucleotides
95
Why is the pentose phosphate pathway essential in RBC
Maintains free -SH groups on cysteine residues
96
Why is the pentose phosphate pathway essential in adipose tissue
Provides NADPH for lipid synthesis
97
Where does the c5 sugar ribose come from for nucleotides
Pentose phosphate pathway
98
How much ATP is generated in the pentose phosphate pathway
Nil
99
What is the start product in the pentose phosphate pathway
G6P
100
What is phase 1 of the pentose phosphate pathway
Start
Enzyme
Product
G6P + 2NADP+
Glucose 6 phosphate dehydrogenase G6PD
C5 + 2NADPH + 2H+ + 2CO2
101
Where is G6PDH located chromosomally
X
102
Why do you get Heinz bodies with a G6PDH defficency?
NADPH (from pentose phosphate pathway)needed to recycle glutathione
Gluatathione protects against free radicals
RBC can only get NADPH from PPP therfore chromatin becomes damaged and haemolysis occurs
103
What happens to the c5 sugars from the PPP that arent used up?
Converted to 2-fructose-6 phosphate and glyceraldehyde-3-phosphate and rejoin glycolysis
104
How is pyruvate inverted to Acetly Coa?
What is produced?
What enzyme ?
Pyruvate dehydrogenase
Co2 produced
NAD+ converted to NADH
105
What is important about the conversion of pyruvate to Acetly coa
Acetly coa can not be used in gluconeogenesis, conversion is large energy step
106
If Acetly coa wasn't under some kind of control, what would happen?
Glucose dependent tissues would use up all of the glycogen stores
107
What other pathway is important so that acetyl coa levels are kept high?
Beta oxidation of fatty acids
108
What inhibits the activity of PDH
Acetly Coa
109
What activates PDH activity
Insulin
110
What are the 3 classes of lipids in the body?
Fatty acid derivatives
Hydroxyl-methyl-glutoric-acid derivatives
Vitamins DEAK
111
What are some examples of fatty acid derivatives?
Fatty acids
Triacyglycerol
Phospholipids
Eicasonoids
112
What are some examples of hydroxy-methyl-glutamic acid derivatives
Ketone bodies
Cholesterol
Cholesterol esters
Bile salts
113
The breakdown of triacyglycerol is called what? And the build up of it is called what?
Lipolysis
| Esterfication
114
Triacyglycerol have what properties
Anhydrous
| Hydrophobic
115
What promotes esterfication and what promotes lipolysis hormonally
Insulin promotes esterfication
| Glucagon, cortisol, adrenaline, growth hormone and thyroxine promote lipolysis
116
What enzyme is responsible for the breakdown of triacyglycerols
Hormone sensitive lipase
117
Once TAG has been broken down, how and where do the components travel
Glycerol in the blood to the liver
| Fatty acids bound to albumin to tissues
118
When glycerol reaches the liver what enzyme acts on it?
What does it make?
Where can this new component now go ?
Glycerol kinase
Glycerol phosphate
Glycerol phosphate can now be used either for TAG synthesis or to enter glycolyis by conversion to dihydroxyacetone phosphate
119
Where can fatty acids not be utilised? Why is this?
RBC- no mitochondria
| Brain- cant cross BBB
120
When fatty acids reach a desired tissue what reaction takes place?
What enzyme
Where in the cell
CoA added to make fatty accyl CoA
Fatty Acyl CoA synthase
Outside the mitochondira
121
What is the purpose of linking fatty acids to CoA?
Form high energy of hydrolysis bond
122
How does fatty accyl CoA enter the mitochondria for beta oxidation
Transport using carinitine?
123
What inhibits the transport of fatty acyl CoA into the mitochondria?
Why does it do this?
Malonyl CoA- an intermediate in fatty acid synthesis
| Stops newly synthesised fatty acids entering mitochondria
124
What happens in beta oxidation within the mitochodnria?
A sequence of oxidative reactions to remove C2 at a time, the c2 compound goes on to for Acetly CoA
125
What is essential for beta oxidation to occur?
Oxygen as the reducing agents need to be reoxidised by ETC
126
What are ketone bodies?
Important fuel molecules used by all tissues, including the CNS
127
What are the 3 ketone bodies produced in the body?
Acetoacetate, acetone, beta hydroxybutyrate
128
How are high plasma concentrations of ketone bodies possible?
They are water soluble
129
What levels of ketone bodies is normal in a restin state?
Less than 1 mol
130
What level of ketone bodies can be seen in starvation
2-10mol
131
If ketone level is above 10 what is likely they case?
Untreated type 1 DM
132
Which ketone bodies are strong organic acids?
Acetoacetate
| Beta hydroxybutyrate
133
What does the ketone body acetone account for?
Nail varnish breath, its volatile
134
What 2 things do you need for ketone synthesis?
Available fatty acids
| Fall in plasma insulin level
135
What are ketone bodies synthesised from
Acetly CoA
136
What enzyme catalyses the precursor for ketone body formation from Acetly coa?
Synthase
137
What enzyme converts HMG COA to mevalonate?
What does this go on to form?
What drugs target this enzyme?
HMG CoA reductase
Mevalonate goes on to form cholesterol
The enzyme is a target for statins
138
What enzyme is needed to convert HMG CoA into ketone bodies?
Lyase
139
What does lyase convert HMG CoA into?
Acetoacetate
140
What does acetoacetate go on to form?
Acetone via spontanous non enzymatic decarboxylation
| Beta hydroxybutyrate
141
Ketone body formation is controlled by what?
Insulin/glucagon ratio
| Glucagon activates ketone formation, insulin inhibits
142
What effect does insulin have on lyase and HMG reductase
Inhibits lyase, activates reductase
143
What is ketonuria?
Ketone level reaching above renal threshold and ending up detectable in urine
144
When are ketone bodies primarily utilised?
In starvation
145
How much of alcohol is metbolised and how much is excreted?
90% metabolised
| 10% excreted
146
What 2 enzymes are key in the metabolis of alcohol?
Alcohol dehydrogenase
| Aldehyde dehydrogenase
147
What is alcohol converted to initially?
What enzyme
What is the issue with the intermediate?
Acetaldehyde
Alcohol dehydrogenase
Acetaldehyde is toxic to cells
148
How is the fact that the intermediate of alcohol metabolism- acetaldehyde being toxic to the cells compensated for by the body?
Aldehyde dehydrogenase has a very low Km for acetaldehyde
149
What is the end product of alcohol metabolism, where does it go on to?
Acetate-> acetyl coa to TCA
150
What happens if acetaldehyde accumulates?
Liver damage
Hyperbillirubaemia
Hyperammonaeamia
Decreased synthesis of clotting proteins and albumin
151
How is liver damage detected e.g from alcohol damage?
Leaky plasma membranes- transaminases and gamma glutanmyl transpeptidase leak out
152
If there is reduced ability to produce urea due to liver damage, what will occur
Hyperammonaemia
| Raised glutamine
153
Why do you get fatty liver with alcohol intake?
Liver damage means inability to produce adequate lipoproteins, they accumulate in the liver.
154
Other than accumulation of acetaldehyde what other issue is there with processing excess alcohol?
Uses up the NAD+ as NADH levels rise. Decreased ability to oxidise anything
155
If the NADH levels are very high due to alcohol metabolism, what are some resultant issues?
Inability to oxidise fatty acids
Can't convert lactate to pyruvate
Can't metabolise glycerol
156
If the NADH levels are high due to alcohol metabolism, and the lactate cant be converted to pyruvate, what is the knock on effect
Lactic acidosis
Decreases kidneys ability to excrete Uric acid
Uric acid builds up contributing to gout
157
If there is decreased levels of NAD+ due to alcohol metabolism, and therfore an inability to use glycerol and lactate. What is the outcome?
Decreased gluconeogensis
| Danger of hypoglycaemia
158
What are the 4 big consequences of the increased NADH in alcohol metabolism?
Lactic acidosis
Urate crystal formation
Hypoglycaemia
Fatty liver
159
What 4 specific defficencies of nutrients does excess alcohol intake cause?
What can they lead to?
Thiamine and pyrixodine- neurological sx
Folic acid- anaemia
Thiamine- korsacoffs
160
What can chronic alcohol intake do to the pancreas
Cause chronic pancreatitis
161
What is disulfirams purpose?
Inhibits aldehyde dehydrogenase resulting in acetaldehyde build up and feeling of extreme nausea
162
What are fatty acids synthesised from? What does it require?
Acetly coa
| Requires ATP and NADPH
163
What is acetyl CoA converted into?
What enzyme catalyses it?
What's needed?
What change has it made?
Malonyl CoA
Acetyl CoA carboxylase
ATP
C2-> C3
164
When Malonyl CoA is enters the fatty acid synthase complex what is released?
CO2
165
Where does lipogensis occur?
Liver cell cytoplasm
166
Where is the NADPH coming from for lipogenesis?
| What needs it?
PPP, TCA
| Fatty acid synthase complex
167
What is the fatty acid synthase complex?
| Why is it less important than the Acetly CoA carboxylase?
Group of enzymes that work together to form fatty acids
| It isn't a control step like Acetly coa carboxylase
168
How is acetyl coa carboxylase activity controlled?
Citrate and insulin activate it
| AMP, Glucagon and adrenaline inhibit it
169
Once the fatty acid is made, where does the glycerol come from?
The glycolysis pathway
170
What is the TAG synthesised from lipogenesis transported out the liver as/in
VLDL
171
What is the function of chylomicrons?
Transport dietary TAG to tissues like adipose
172
What is the function of VLDL
Transport TAG synthesised in liver to adipose for storage
173
What is the function of IDL
Short lived precursor of LDL, transporting cholesterol from liver
174
What is the function of LDL
Cholesterol transport from liver to tissues
175
What is the function of HDl
Transport excess tissue cholesterol to the liver for disposal as bile salts or to other tissues that need it
176
What is 'good cholesterol'
HDL
177
What stimulates uptake of amino acids into tissues?
Insulin and growth hormone
178
What promotes breakdown or nitrogen based compounds (proteolysis)
Cortisol
179
What is the majority of body protein in the form of?
90% DNA and RNA
| 10% purines, pyramidines, neurotransmitters, creatine etc
180
How much of the amino acid pool is resynthesised back to body proteins?
75%
181
Hoe are nitrogen containining compounds lost from the body?
In faeces and urine as urea, creatine, ammonia, Uric acid
| As hair and skin
182
Where are non essential amino acids made from?
Intermediates of glycolysis for carbon base chain
| Transammination or ammonia for the amino group
183
What cycles supply the carbon based chains for non Essential amino acids?
Glycolysis C3
PPP C4, C5
Krebs C4, C5
184
What happens to excess dietary amino acids??
Converted to intermediates of carbohydrate or lipid metabolism
185
What are 2 important signalling molecule that come from amino acids?
Nitric oxide from L arginine
| Hydrogen sulphide from L cytstein
186
Where is the main site of amino breakdown?
The liver
187
Although each amino has is own metabolic pathway, what 3 common features do all the pathways share
The Carbon atoms are converted into intermediates for carbohydrate or lipid metabolism
The NH2 group is removed (trans or deam)
The N atoms are usually converted to urea
188
When converting an amino acid to a carbohydrate intermediate, what are the 2 categories
Glucogenic
Ketogenic
(Some are both)
189
What can glucogenic amino acids form
Glucose- eg pyruvate, oxeloacetate, alpha ketoglutarate succinyl
190
How many amino acids are glucogenic?
14
191
What are the ketogenic only amino acids
Leucine
| Lysine
192
What can ketogenic amino acids make?
Ketone bodes and fatty acids- eg Acetyl coa
193
What amino acids are both glucogenic and ketogenic
Isoleucine
Tyrosine
Phenylalanine
Tryptophan
194
What stimulates transamination
Cortisol
195
What do most amino acids use as the keto acid in transamination
Alpha ketoglutarate
196
What is the general formula of transamination?
Amino acid + keto acid -Aminotransferase-> keto acid+ amino acid
197
If alpha ketoglutarate is the keto acid being used in by an aminotrasferase, what is the resultant amino acid. And what happens to that amino acid?
Glutamate
| Either re-used or deammination
198
What transaminase differs in that it does use alpha ketoglutarate at keto acid 1?
What does it use?
What amino acid does it produce?
Aspartate aminotransferase
Uses oxaloacetate
Amino acid produced is aspartate
199
What are the 2 transaminases commonly measured?
ALT
| AST
200
What is deamminaton
Removal of NH2- from amino as Nh3+
201
What enzymes do we possess that deamminate
L and D amino oxidisas
202
Why do we have lots of D amino acid oxidases?
We don't use D amino acids in protein synthesis but they need to be processed.
203
What enzyme is responsible for deamination of glutamine?
| What does it produce?
Glutaminase
| Glutamate and NH3+
204
Glutamate (deaminated from glutamine) is processed further how?
What is the direction of this reaction determined by?
Glutamate dehydrogenase converts it to alpha ketoglutarate and Nh4+
The direction is determined by the relative concentrations
205
At what level is ammonia kept at in the body?
What is particularly sensitive to hyperammonia?
What symptoms are associated?
25-40nmol
CNS
Blurred vision, tremors, slurred speech, coma, death
206
How is ammonia mostly processed?
Detoxification in the liver by either converting it to urea or using it in N compound synthesis
207
What is ammonia mainly converted to(N compound)?
Glutamine
208
How does the liver convert ammonia to glutamine?
(Additional compounds needed)
(Enzyme)
Nh4+ + glutamate + ATP -> Glutamine + ADP + Pi
| Glutamine synthase
209
Once glutamine synthase has made glutamine from ammonia and glutamate, what happens to it?
What enzyme is involved
It's transported to the kidney to make urea
| Glutaminase converts it to NH4 and glutamate.
210
Why is urea so damn good as a method of excreting nitrogen
It's inert and 47% nitrogen
211
Is the urea cycle subject to feedback inhibition?
No but it does become induced. High protein diet=more enzymes
212
What is refeeding syndrome? What happens
Due to low protein diet the urea cycle is induced to having low levels of enzymes to make urea
Sudden increase results in hyperammonia
213
What cycle does the urea cycle overlap with
TCA
214
After glycogen stores are depleted what does the body need to do?
Gluconeogenesis
215
What can be used in gluconeogenesis
Pyruvate
Lactate
Glycerol
Essential and non essential amino acids
216
What cant be used in gluconeogenesis? Why?
Acetly Coa
| PDH is irreversible
217
How many steps of glycolysis are reversible?
7
218
What steps of glycolysis are not reversible and therefore need a seperate mechanism in gluconeogenesis?
1, 3 and 10
219
How is reaction 1 altered in gluconeogenesis?
Enzyme
Regulation
G6P+ H20 -> glucose
Glucose 6 phosphotase
Thermodynamically spontaneous
220
How is reaction 3 of glycolysis altered in gluconeogenesis?
Enzyme
Method
Fructose 1,6 bisphosphate + H20-> fructose 6 phosphate
Fructose 1,6 bisphosphotase
Thermodynamically spontaneous
221
What does pyruvate need to be converted to first before step 10 of glycolysis? What enzyme is needed? What else is needed?
Oxaloacetate
Pyruvate carboxylase
ATP + CO2
222
How is step 10 reversed in gluconeogenesis. Pyruvate has already been converted to oxaloacetate using pyruvate carboxylase. What next?
End product
Enzyme
Require components
Oxaloacetate-> phosphenolpyruvate +CO2
Phosphoenolpyruvate carboxykinase PEPCK
GTP drives it
223
What mainly controls rate of gluconeogenesis?
Hormonal control (glucagon and insulin)
224
What inhibits PEPCK and fructose 1,6 bisphosphotase?
Insulin
225
What stimulates PEPCK and fructose 1,6 bisphosphotase
Glucagon
226
In diabetes, what is the outcome of gluconeogenesis?
No insulin means gluconeogenesis is stimulated, contributing to hyperglycaemia
227
The TCA cycle occurs where
Mitochondria
228
What is the Acetly coa converted into by going through the TCA cycle
2 CO2
229
What does the TCA produce?
Some ATP, some NADH, FADH2,GTP
| Precursors for biosynthesis
230
What does the TCA not function without
O2
231
How many ATP are directly produced from TCA
2
232
After the TCA how many net molecules of ATP have been produced?
4
233
In the TCA Acetly Coa is converted into what by getting added on to what?
Acetyl coa (c2) + oxaloacetate (c4)-> citrate (c6)
234
Citrate is converted into ISO citrate in the TCA. What is the next step?
Enzyme
Products
Isocitrate(C6)-> alpha ketoglutarate (C5)+CO2
Isocitrate dehydrogenase
NAD+ -> NADH
235
Alpha ketoglutarate (C5) in the TCA (converted form iso-citrate) goes on to form what?
Enzyme
Products
Alpha ketoglutarate (C5) + CoA -> Succinyl-CoA (C4) + CO2
Alpha ketoglutarate dehydrogenase
NAD+ -> NADH
236
```
Succinylcholine CoA (C4)(in TCA) is converted to what
What are the products
```
Succinate (C4)+ CoA
| GDP-> GTP
237
What is converted to oxaloacetate in the TCA
Malate
238
In the TCA what molecules are precursors for amino acids (and where amino acids can feed into TCA)
Malate
Oxaloacetate
Alpha ketoglutarate
Succinate
239
What molecule in the TCA goes on in the synthesis of haem?
Succinate
240
What molecule in TCA goes on to form fatty acids?
Citrate
241
At the end of TCA what has happened to the original glucose molecule
All C-C bonds broken
All C atoms oxidised to CO2
All C-H bonds broken
H atoms transferrred to NADH or similar
242
What is the electron transport chains purpose?
Released energy providing free energy to drive ATP synthesis with oxidative phosphorylation
243
What do PTCs set up in the ETC
The proton motive force
244
What is the proton motive force?
Electrochemical gradient of protons on the intermembrane space, wanting to move to the inner membrane
245
Once the PTC have set up the PMF, what happens
ATP synthase provides the only route back. It drives the synthesis of ATP
246
How much energy is actually used in moving the H+ across the membrane? What happens to the rest
30% the rest is lost as heat
247
How is the ETC regulated?
If atp is high there is no substrate (ADP) for atp synthase to use, this increases the H+ in the intermembrane space, this stops the H+ pump (reverse with low atp)
248
What do uncouplers do in relation to the ETC
Increase permeability of the mitochondrial membrane to protons, dissipating the PMF
249
What does brown adipose tissue have to generate heat
Thermogenin (ETC uncoupler)
250
What is creatine phosphate
Small energy store in cardiac and skeletal muscle
251
When is creatine phosphate production favoured/
When atp is high
252
How is creatine phosphate produced
| Enzyme
Creatine + ATP-> creatine phosphate and adp
| Creatine kinase
253
What is creatinine?
How's it made
What do its levels indicate
It's a breakdown product of creatine and creatine phosphate
Non enzymatic change
High levels seen when muscle breakdown levels high (could be due to large muscle mass or pathological)
254
What does a high blood creatine and a low urine creatine indicate?
Impaired kidney function
255
What is iron stored in the liver as?
Ferritin and haemosiderin
256
What is ferritin?
Protein with capacity of about 4500 iron ions
257
The iron stored as a complex in haemosiderin differs from ferritin stored iron how?
It is physiologically acitive
258
What is ferritin?
Protein with capacity of about 4500 iron ions
259
What's DMT1
Duodenal metal transformer 1- transports ferrous iron
260
Where calcitonin produced?
Parafollicular cells of the thyroid
261
What does calcitonin do?
Reduce blood calcium levels, opposing parathyroid hormone
262
What's fatty acyl synthase?
Multi enzyme protein that catalyses fatty acid synthesis
263
What surgery is used for pituatry tumours?
Transphonoidal
264
When is blood cortisol tested?
Midnight
265
What is TAILS in reference to microcytic anaemia causes?
```
Thalassaemia
Anaemia of chronic disease (can be normo)
Iron defficent anaemia
Lead poisoning
Sideroblastic anaemia
```
266
What are the endocrine cells of the pancreas?
Islets of langerhann
267
What phosphate is hydrolysed for work in atp
Y
268
What is the action of metformin?
Inhibit hepatic gluconeogenesis lowering plasma glucose
269
What are the 4proteins of the RBC cell membrane
Ankyrin, spectrin, protein 4.2 and band 3
270
What vitamin protects against lipid peroxidation?
Vitamin E
271
What's a broken fragmented rbc called
Schistocyte
272
If Gibbs free energy is below 0 the reaction is what?
Exergonic
273
Equation for BMI
Kg/ height in M squared
274
Where is the energy bond in ATP
Between beta and gamma phosphate
275
10 calories is how many kilojoules?
42 (x4.2)
276
What's carbohydrates general formula?
(CH2O)n
277
What is the formulae for aldehyde?
| What is it for keto group?
C=OH aldehyde
| C=O keto
278
What are the disaccharides sucrose, maltose and lactose made up of?
Sucrose- glucose and fructose
Maltose glucose x2
Lactose- galactose and glucose
279
What are routine maintainance iv fluids made up of?
1mmol/kg/day of Na+, K+ and Cl-
| 30ml/kg/day of water
280
A deficency in vitamin a results in what?
Xerophthalmia
281
Deficency in vit d results in what
Rickets
282
Deficency in vit E results in what?
Neurological abnormalities
283
Deficency in vitamin K results in what
Clotting abnormalities
284
Examples of dietary fibre include?
Cellulose, lignin, pectins, gums
285
Cellulose is a polymer of what?
Glucose with beta 1,4 bonds
286
What's the RDI fibre
18g
287
What are some risks of low dietary fibre
Constipation, bowel cancer.
| High fibre decreases cholesterol
288
What is daily energy expenditure comprised of?
BMR+ diet induced thermogenesis + Physical activity
289
What's BMR
Energy required to maintain cellular function
290
What's BMI
Kg/M2
291
What's an alternative measure to BMI
Waist hip ratio
292
What's kwashiorkor disease
Low protein dietary resulting in insufficient plasma oncotic pressure and oedema
293
What is pancreatic amylases role when a disaccharide attaches to the brush border?
Breaking alpha 1,4 glycosidic bonds
294
What's isomaltases role when a dissacharide attaches to the brush border?
Breaking alpha 1,6 glycosidic bonds
295
What is primary lactase deficency likely due to/
Absence in lactate persistence allele
296
What's secondary lactase deficency likely due to?
Injury to the small intestine eg crohns or ulcerative colitis
297
How is glucose absorbed into intestinal epithelial cells?
Sodium dependent glucose transporter 1 SDGL1
298
Once the sodium dependent glucose transporter has taken glucose into the cell what puts it into the blood supply?
GLUT 2
299
GLUT2 receptors for glucose are located were? What's important about them?
Kidney
Liver
Pancreatic
Small intestine
They arent regulated by insulin
300
GLUT4 receptors are found where for glucose?
Striated muscle and adipose tissue
301
What are some cells that have an absolute glucose requirement? And why is that?
RBC- no mitochondria
Neutrophil- mitochondria needed for resp burst
Inner kidney medulla- low o2
Lens of eye
302
What does the CNS use for energy
Primarily glucose, also ketone bodies
303
Where does glycolysis take place?
Cytosol
304
What are the 2 stages of glycolysis
Investment -2atp
| Payback +4 atp
305
What's the difference between hexokinase and glucokinase
Hexokinase is not in the liver and is inhibited by its product G6P
306
What happens to glucose uptake in cancer cells? Why is that relevant?
Increases up to 200x
| Imaging with radioactive hexokinase
307
How is PFK regulated?
Allosterically in muscle by ATP: ADP ratio
| Hormonally in liver by insulin: glucagon ratio
308
What is glycerol 3 phosphates role?
Convert dihydroxyacetone-P to glycerol phosphate for TAG synthesis
309
What is BPG mutase role?
Conver 1-3 BPG to 2-3 BPG
310
What is the purpose of lactate production?
Regenerate NAD+
311
When is the conversion of lactate back to pyruvate by LDH impaired?
Alcohol metabolism
Liver disease
Thiamine defficency
312
A lactate of 2-5mm is what? What happens?
Hyperlactaemia, no change in PH due to buffering capacity of blood
313
When lactate exceeds 5 mmol what happens
PH change of blood
314
What are the 3 enzymes of galactose metabolism
Galactokinase
Uridyl transferase
UDP galactose epimerase
315
What enzymes are involved in fructose metabolism? What do there defficencies result in?
Fructokinase (fructosemia)
| Aldolase ( F1P accumulation and liver damage)
316
What is the role of the PPP
Produce C5 intermediate
| Source of NADPH for biosynthesis
317
Main enzyme in the PPP
G6PDH
318
How is pyruvate kinase controlled in glycolysis
Insulin:glucagon ratio
319
How else is glycolysis controlled, not at an enzymatic level?
Metabolically by NADH;NAD ratio
320
PDH is a large multienzyme complex made of how many enzymes?
What deficency is it sensitive too (req for its cofactors)?
What does it do?
5
B1 vitamin
Reduce pyruvate to Acetly coa
321
With a deficency in PDH what is seen in the blood?
Lactic acidosis
322
What inhibits PDH, what activate it?
Inhibit: Acetly coa, Citrate (forward product), NADH, ATP (high energy)
Stimulate: pyruvate, ADP, NAD+, insulin
323
What does Acetly coA combine with in the TCA to form?
Combines with oxeloacetate to form citrate
324
What are the 2 steps in TCA where CO2 is lost? What enzymes facilitate this?
Isocitrate-> ketoglutarate (isocitrate dehydrogenase)
| Alpha ketoglutarate-> succinyl coa (alpha ketoglutarate dehydorgenase)
325
How many cycles of the TCA for each molecule of glucose?
2
326
What are present in the mitochondria to set up the PMF
Proton translocating complexes PTC
327
How is the electron transport chain regulated?
In high ATP there is less substrate for ATP synthase to use, H+ builds up in the intermembrane and this inhibits the PTC pump
328
What is the difference between an inhibitor of the ETC and an uncoupler?
An inhibitor blocks the ETC resulting in no PMF
| Uncouplers increase the permeability of the mitochondira to protons resulting in less effective PMF generation
329
What does brown adipose tissue have a lot of for heat production
Thermogenin
330
What are some key features of oxidative phosphorylation
Requires membrane complexes
Indirect energy coupling
Can't occur in abscence of oxygen
Minor process in atp generation
331
What are some key features of substrate level phosphorylation
Requires enzymes
Direct energy coupling
Can occur without o2
Minor process of atp production
332
What do phospholipids have as well as the carbon, hydrogen and oxygen you would see in a lipid?
P and N
333
The average man 70kg would approx how much TAG? How much would an obese 100kg man have roughly?
15kg
| 45kg
334
A chylomicron can go where? Where can it not go?
Adipose tissues for storage
Consumer tissue for utilisation of fatty acids
Can't go RBC, WBC (mitochondria needed) or brain as BBB
335
How can excess glucose be stored as fat?
Converted to glycerol 1 p
| Combine with fatty acyl coa in esterfication
336
Why are there essential polyunsaturated fats like linolenic acid?
Because the body cant synthesise double bonds after c9 compound.
337
What are the 3 steps in fatty acids metabolism and where are they occuring
1- fatty acyl coa synthase links CoA to the fatty acid (outside mito)
2. Carnitine shuttle transports into mitochondria (inhibited by malonyl coa)
3. Beta oxidation
338
How can glycerol be utilised? Both anabolically and catabolically.
1. Glycerol kinase enzyme used to make glycerol phosphate in liver
2. Then can anabolically combine with fatty acids to make tag or be synthesised into DHAP and enter glycolysis
339
How can acetyl CoA be used anabolically and catabolically
Catabolic- TCA
Anabolic- fatty acid synthesis (fatty acyl synthase and Acetly coa carboxylase)
Cholesterol/ ketone bodies (HMG CoA +/- reductase or lyase)
340
If insulin is high what is more likely to be formed cholesterol or ketone bodies?
Cholesterol
341
If glucagon is high what is more likely to be formed from HMG?
Ketone bodies rather than cholesterol
342
What is the target of statins?
HMG CoA reductase
343
What are 2 outcomes of high ketone bodies?
Ketoacidosis (acetoacetate and beta hydroxybutyrate strong organic acids)
Ketouria (above renal threshold)
344
How are lipids hydrolysed in digestion?
Pancreatic lipases
345
Hormone sensitive lipase is upregulated how?
Increased glucagon
346
How are fatty acids carried to tissues for utilisation?
Bound to albumin as fatty acid complex
347
What is the general formula for esterfication
Glycerol 1-P +fatty acyl coA-> TAG
348
What's the general formula of lysis of a TAG
TAG-> fatty acid (bound to albumin in blood)+ Glycerol
349
How is a fatty acid re-esterfied?
Conversion to fatty acyl coa
350
Where are ketone bodies synthesised?
Liver mitochondira
351
What's HMG CoA synthase role?
To make HMG CoA from Acetly CoA
352
What's the calorie requirement for the BMR of average person of 70kg
1700 (x4.2 for kj)
353
What's an exergonic reaction?
Releases energy, -ve Gibbs
354
Is NAD+ reduced?
No its oxidised
355
What is an indicator of muscle breakdown?
Creatinine
356
What does creatine kinase enzymatically work on?
Conversion of creatine to phosphocreatine
357
What is alcohol broken down into (end product after acetaldehyde dehydrogenase) what is that then used for?
Acetate-> acetyl coa for glycolysis or tag synthesis
358
What other things can oxidise alcohol?
Cyp450- cypb2e
| Catalase in brain
359
How many units of alcohol are recommended per week?
How many in half a pint?
How quickly do we get rid of alcohol
14 spread over at least 3 days
1 unit, 8g alcohol
7g per hour
360
What do free radicals damage?
Nucleic acids, proteins, lipids.
361
Is hydrogen peroxide a free radical?
No but can create hydroxyl radical when it reacts with iron in Fenton reaction
362
How can ROS damage DNA
React with base resulting in modified base that can cause mispairing
React with sugar backbone causing strand break
363
How can ROS damage protein
Damage backbone causing fragmentation
| Damage side chain altering function
364
What bonds can ROS cause?
Inappropriate disulphide bonds
365
What effect can ROS have on lipids?
Lipid peroxidation
366
What uses resp burst?
| What's released?
Neutrophils, macrophages
| Superoxide, hydrogen peroxide
367
How does superoxide dismutase and catalase work together to manage ROS
Superoxide dismutase converts superoxide to H2O2 and oxygen
| Catalase converts H2O2 to H2O and oxygen
368
What does glutathione (GSH) have that makes it an antioxidant?
What enzyme?
An electron to donate with the help of enzyme glutathione peroxidase.
It makes a double bond with another GSH to make GSSG
369
How is GSSG converted back to GSH for anti-oxidant properties?
What enzyme
What else does it need and where does it get it from?
Glutathione reductase
| Needs NADPH from PPP
370
Why do you get Heinz bodies with G6PDH defficency
No NADPH to regenerate glutathione resulting in ROS damage to haemoglobin
371
Why do you get damage to the lens of the eye with galactasamia
Aldose reductase uses up all NADPH so glutathione regen cant happen and ROS damage lens
372
How do Vit E and Vit C work together as antioxidants
Vit E is a free radical scavenger. Vit C regenerates vit E to its active form
373
How is paracetemol normally metabolised? Not in toxic dose
Conjugation with glucorinide or sulphate and then excreted
374
What happens when there is toxic levels of paracetemol?
NADPQ1 accumulates. Direct toxic effect to lipids, proteins, dna.
Also decreases glutathione leading to ROS damage
375
What is given in paracetemol overdose? Why
Aceylcysteine to replenish glutathione
376
What is a measure of oxidative Dave
Amount of 8-oxo-dog
377
What is chronic granulomatous disease a result of?
Genetic defect in NADPH oxidase complex.
No NADPH means no resp burst
Enhances susceptibility to bacterial infection
378
Some symptoms of galactosaemia?
```
Hepatomegally
Renal failure
Seizures
Hypoglycaemia
Cataracts
```
379
Name a glucogenic, ketogenic and either type of amino acid
Glucogenic- glycine
Ketogenic- leucine
Both- isoleucine
380
What makes up an amino acid?
| What bonds do they form?
Amine group, carboxyl group and a variable r region
| Peptide bonds
381
What coenzyme do aminotransferases from
B6 vitamin derivative
382
Why does a UTI smell?
Bacteria breakdown releasing ammonia
383
How can high levels of ammonia give us issues?
Disrupts cerebral blood flow
Makes ph more alkaline
Interferes with amino acid neurotransmitters
384
What important nitrogen containing compound is found in skeletal muscle?
Creatine
385
Why is meat protein a favourable source of amino acids
Has all essential aminos
386
What do most amino transferase use as substrate and product? What's the exception
Most use conversion of alpha ketoglutarate to glutamate
| Aspartate aminotransferase uses oxaloacetate to aspartate
387
What does ALT do?
| What does AST do?
ALT- alanine to glutamate
| AST- glutamate to aspartate
388
What is deammination?
Liberation of amino group as free ammonia
389
What enzymes can deaminate?
Amino acid oxidases
Glutaminase
Glutamate dehydrogenase
390
Defects in the urea cycle result in what generally?
Hyperammonia
| Accumulation or excretion of urea cycle intermediates
391
What are 2 mechanisms for disposal of ammonia from tissues?
1. Combine with glutamate to make glutamine. Travels to liver where glutaminase converts it back. Or to kidney where ammmonia directly excreted
2. Combine with pyruvate to make alanine. Travel to liver where ALT transaminases it
392
What is phenylketonuria a defficency of?
Phenylalanine hydroxylase
393
What is the outcome of phenylketonuria (due to defficent in phenylalanine hydroxylase)
```
Phenylketones in urine
Less tyrosine (phenylalanine converted product)
```
394
What's homocystinuria a defficency in?
Cystathione beta synthase
395
In homocystinuria what accumulates?
Methionine and homocysteine
396
What's normal blood glucose level
5mmmol/litre
397
What's a marker for diabetes?
Glycated haemaglobin c
398
What's the central protein in glycogen?
Glycogenin
399
What enzyme converts glucose 1 phosphate to UDP glucose for glycogen storage?
G1p uridyltransferase
400
How do muscles keep the glucose 6 phosphate within the muscle when it has been broken down from glycogen?
Lack of glucose 6 phosphotase enzyme
401
How is muscle glucagon alloserically regulated?
AMP an activator of glycogen phosphorylase
402
Importantly what do LDL lack and what does that result in?
They lack apoC and apoE. They are not efficiently cleared by the liver.
Longer half life increases susceptibility to oxidative damage and therefore the chance of getting taken up by macrophages to form foam cells.
403
What do cells requiring cholesterol express?
| What acts as a ligand for this receptor
LDL receptors
| ApoB-100 on LDL acts as ligand
404
What is LDL receptor expression controlled by?
Cholesterol concentration of the cell
405
What's the difference between a Micelle and a liposome
Micelle is single layer of phospholipid and liposome double
406
What is cholesterol essential for? 3
| How is it transported around the body? What enzyme
Components of membranes modulating fluidity
Steroid precursor
Bile acid precursor
Transported as cholesterol ester
Enzyme LCAT
407
What does a lipoprotein have?
| What are the 5 distinct classes?
Phospholipid monolayer
Peripheral and integral apolipoproteins
Cargo- TAG, cholesterol ester, DEAK
VLDL, IDL, LDL, HDL, chylomicron
408
When are chylomicrons normally present in the blood?
4-6h after a meal
409
What apolipoproteins are important in VLDL, IDL, LDL and HDL?
ApoB in VLDL, IDL, LDL
| ApoAI in HDL
410
How does a chylomicron know to deposit its cargo to adipocytes and muscle?
ApoC binds to lipoprotein lipase.
411
What apolipoproteins binds to hepatocytes?
apoE
412
What is HDL role?
Reverse cholesterol transport. Removes cholesterol from cholserol laden cells.
ABCA1 protein within cell facilitates transfer of cholesterol to HDL
Converted to ester with LCAT
413
What is the fate of mature HDL?
Taken up by liver
Scavenger receptor on cells requiring cholesterol
Exchange cholesterol for TAG with VLDL via cholesterol exchange transfer protein
414
What do chylomicrons transport?
VLDL
LDL
HDL
Chylo- TAG from diet
VLDL- TAG from liver
LDL- cholesterol from liver
HDL- excess cholesterol
415
What are 3 clincal signs of high levels of blood cholesterol?
Xanthelasma- yellow eyelid patches
tendon Xanthoma- nodules on tendon
Corneal Arcus- white circle around eye
416
Treatment of hyperlipoproteinaemias ?
States- inhibit HMG CoA Reductase
Bile salt sequestrant- forces liver to produce more bile acids using up cholesterol
DIet and exercise
417
What does protein deficency in children results in?
Growth failure
Impaired physical development
Impaired mental development
Negative nitrogen balance
Oedema due to lack of albumin
Increased risk of infection due to reduced immunoglobulin
Anaemia due to reduced haemoglobin synthesis
Fatty liver due to reduced Lipoprotein synthesis
418
Why are the CNS and heart particularly succeptible to damage in low energy stages, ie ischaemia
Both lack fuel storage therefore require constant supply (CNS specifically glucose and ketone)
419
What would skeletal muscle use in times of anaerobic metabolism?
Glycogen as fuel
| Myoglobin for oxygen
420
A 30 year old woman presenting with stomach pain and diarrhoea after smashing 15 litres of milk likely has what?
Lactase defficency
421
How is lactate processed in the heart compared to the liver?
Heart- pyruvate from lactate is oxidised via TCA
| Liver- could be oxidised but most pyruvate gets converted to glucose.
422
When raised lactate seen?
Raised production- meal, shock, exercise, heart disease
| Reduced utilisation- liver disease, thiamine defficency, alcohol metabolism
423
What is the specific need for glycolysis in RBC (apart from energy)
Production of 2,3 BPG from 1,3 BPG
424
What is the specific use of glycolysis in adipose cells (not energy production)
Glycerol phosphate production from dihydroxyacetone phosphate for esterfication of fatty acids
425
What is PDH relation under control mechanisms for? What does it ensure?
Acetyl coa from beta oxidation of fart acids rather than glucose as Acetly coa inhibits it
Enzyme activated when there is plenty of glucose to catabolise (insulin)
Ensures glucose isn't rapidly used up
426
What is used in the ETC to move protons from the inside to the outside of the inner membrane?
Free energy
427
What is required for ketone synthesis
Fatty acids available for oxidation following excessive lipolysis
Fall in plasma insulin
428
What is inadequate for fatty acid oxidation in alcohol metabolism?
NAD+ as acetaldehyde and alcohol dehydrogenase produce NADH
429
Why do TAGS accumulate with alcohol (in liver)
Increased TAG synthesis and a reduced capacity for the liver to export these due to lower lipoprotein synthesis
430
How are superoxide radicals produced in the mitochondria
During oxidative phosphorylation about 0.1 - 2% of electrons do not reach the end of the electron transport chain and they prematurely reduce oxygen to from superoxide radicals (O2 -).
431
Name some agents that protect the cell against reactive oxygen species
```
Superoxide dismutase
Catalase
Glutathione
NADPH
Antioxidant C and E vit
```
432
What is the relationship between NADPH and glutathione
NADPH reduces oxidise glutathione to its reduced form via the enzyme GSH reductase
433
How is the respiritory burst created in leukocytes
Produced by a member a bound enzyme complex termed NADPH oxidase
434
What is an early step in the catabolism of amino acids?
Removal of amino group to be converted to uraea
435
What do ketogenic amino acids produce?
Acetly Coa
436
What do glucogenic amino acids produce
Products that can be used fro glucose synthesis
437
What are L and D amino acid oxidases
Enzymes that have low specificity to convert amino acids to keto acids and NH3
438
What is Glutaminase?
High specificity enzyme that converts glutamine to glutamate and NH3
439
What is glutamate dehydrogenase?
High specificity enzyme that catalyses the reaction of glutamate to alpha ketoglutarate and NH4
440
What precursors can be used for gluconeogenesis
Lactate
Pyruvate
Glycerol
Amino acids
441
What enzyme means liver can export glycogen breakdown products but muscle cant?
Glucose 6 phosphotase
442
Why are TAG more efficient as energy storage than Glycogen?
They are hydrophobic and anhydrous
Whereas glycogen is polar and is stored in water
Also taG more reduced so more energy
443
What is required before beta oxidation can occur of fatty acids
Activation by linking to CoA (requires ATP)
| Carnitine transporter
444
What are some key benefits of lipogensis and fatty acid degredsation not being simple reversal of each other
has more flexibility as different substrates and intermediate
Better controlled as not reciprocal
445
How are TAGS obtained from chylomicrons and VLDLS
Extracellular lipoprotein lipase in capillary beds of tissue
Hydrolysis to fatty acid and glycerol
Fatty acid taken up and re-esterfied to TAG using glycerol from glucose metabolism
446
How is cholesterol obtained from LDL
Receptor mediated endocytosis
447
Why would an individual with a defect in enzyyme lethicin cholesterol acyltrasnferase produce unstable lipoproteins ?
Lipoproteins only stable in spherical shape dependent on ratio of core to surface lipids
Stability restored when suraface lipid converts to core lipid (by LCAT)
Converts cholesterol on surface to cholesterol ester
Deficency results in instability and therefore deposition
448
What is catabolism? Key features
Oxidative and exergonic
| Generates ATP, reducing power and building blocks
449
What is anabolism?
Reductive and endergonic, synthesis of macromolecules
450
What are the bodies normal fuels?
| And special fuels?
Normal- glucose in the form of circulating glucose and glycogen
Fatty acids stored as TAG
Special- amino acids- ketogenic or glucogenic
Ketone- from fatty acids
Lactate- conversion to glucose via cori cycle
451
What's an advantage of using lactate for energy? What cycle?
Cori cycle
| No investment phase as goes in as G6P
452
What are some key points regarding the TCA cycle
4 carbon oxaloacetate and 2 carbon pyruvate make 6 carbon citrate
Isocitrate the key enzyme- inhibited by NADPH and acitvated by ADP
NADH and FADH2 are made and GTP made from substrate level
453
What are some key points re the ETC
Electrons in intermembrane space to pump H+
| Complex 1,3,4 move the H+
454
What are some key points to fatty acid oxidation?
Linked to coenzyme A by fatty acyl coa synthase
Carnitine shuttle to inner membrane that is inhibited by malonyl coa (a fatty acid synthesis intermediate)
Produces NADH and FADH2 and acetate that goes on to Acetly coa
455
What are some key points to ketone body production
Made in liver mitochondria from acetyl coa
| Glucagon activates and insulin inhibits
456
What's the order in which the body uses up fuels as you go from fed to starvation
Glucose-> glycogen->fat-> amino acids, glycerol and lactate-> ketones
457
When glucose is low how is glucose sparred from the muscles?
No glut 4 on cell therfore fatty acids used
458
What happens hormonaly in starvation?
Glucagon and cortisol released causing breakdown of protein and fat
Reduction of insulin and anti insulin affects (preventing cells using glucose)
Glycerol from fat enters gluconeogensis to spare porotein breakdown
459
In muscles how much to myosin atpase account for atp turnover?
70%
460
How would energy systems be used in sprinting
Initial creatine phosphate stored
| Followed by anaerobic glycolysis and muscle glycogen
461
How does exercising muscle get its glucose?
Amp causes glut 4 translocation
462
Fatty acids can sustain exercise for how long? What limits them?
48H
| Carnitine shuttle
