Metabolism Flashcards
1
Q
What is metabolism ?
A
the sum of all chemical reactions in a cell needed to survive , grow and reproduce
2
Q
How do enzymes catalyse reactions that happen at higher temperatures ?
A
they lower the activation energy
3
Q
What happens during catabolic reactions ?
A
breakdown foodstuffs into smaller molecules
4
Q
How does catabolism play a dual role ?
A
energy is released as well as small molecules being released
5
Q
What happens during anabolic reactions ?
A
the energy released from catabolism is used to produce new molecules
6
Q
What is the thermic effect of food ?
A
a high amount of energy is needed to process the food that the net amount of energy released is small
7
Q
What is the units for the energy released from food ?
A
kCal per gram
8
Q
How do organisms extract energy from food ?
A
oxidation
9
Q
What is oxidation ?
A
the removal of electrons
10
Q
What is reduction ?
A
the addition of electrons
11
Q
In chemical reactions how do reduction and oxidation occur ?
A
simultaneously
12
Q
How is energy conserved in reactions ?
A
the number of electrons is conserved
13
Q
What can activated carriers store ?
A
chemical groups
electrons
14
Q
What do activated carriers do ?
A
they act as the link between catabolism and anabolism
15
Q
Energetically favourable reactions ….
A
… can drive unfavourable reactions
16
Q
How does NAD store energy ?
A
in the from of 2 high energy electrons and H atoms
17
Q
What is the precursor of NAD ?
A
niacin vit B3
18
Q
What does NAD deficiency cause ?
A
pellagra - magneta tongue
19
Q
What does FAD deficiency cause ?
A
angular stomatitis
20
Q
During oxidation what happens to ATP
A
ADP is turned to ATP
21
Q
During reduction what happens to ATP ?
A
ATP is turned to ADP
22
Q
How is ATP generated ?
A
in the ETC of substrate level phosphorylation
23
Q
Which chemical groups can activated carriers hold ?
A
acetyl
methyl
carboxyl groups
24
Q
What are the 4 types of enzymatic control ?
A
allosteric
hormonal
rate limiting step
substrate supply
25
What is the rate limiting step ?
an irreversible reaction
| the enzymes that catalyse the reaction are strictly regulated
26
What are allosteric effectors ?
they bind away from the active site
| they can inhibit/activate enzyme activity
27
What is product feedback inhibition ?
when the product of the reaction can act on an earlier component to diminish the response
28
What is hormonal control of enzymes ?
phosphorylation of enzymes that is hormone mediated
| enzyme induction - producing more enzyme - transcription and translation levels are effected
29
Which amino acids are phosphorylated when proteins are phosphorylated ?
serine
tyrosine
threonine
30
`Which enzyme controls protein phosphorylation ?
protein kinase
| protein phosphatase
31
What does compartmentalisation allow ?
metabolic reactions to be controlled separately
32
Where does glycogenesis occur ?
cytosol
33
What are the 3 steps of glycogenesis ?
donor formation
elongation
branching
34
What enzymes are involved in glycogenesis ?
glycogen synthase
| Branching enzyme
35
What is the activated donor in glycogenesis ?
UDP-glucose
36
What activates glycogen synthase ?
Glucose 6 Phosphate
| ATP
37
What inhibits glycogen synthase ?
Glucagon
Adrenaline
they phosphorylate glycogen synthase inactivating it
38
Where does glycogenolysis occur ?
cytosol
39
What is the first step of glycogenolysis ?
removal of glucose units from glycogen
40
What happens after glucose 6 phosphate is made ?
in the liver it is converted to glucose by glucose 6 phosphatase
41
How does debranching happen ?
debranching enzyme removes the distal 3 units
amylo alpha 1,6 glucosidase removes the alpha 1,6 link
this releases free glucose
can be phosphorylated by hexokianse
42
What are the enzymes involved in glycogenolysis ?
glycogen phosphorylase
glucose 6 phosphatase
debranching enzyme
amylo alpha 1,6 glucosidase
43
What stimulates glycogen phosphorylase ?
glucagon and adrenaline
| they phosphorylate
44
Describe a phosphorylation cascade ?
the presence of adrenaline or glucagon in tge blood can cause ATP to be converted to cAMP
cAMP activates protein kinase
protein kinase inhibits Glycogen Synthase
protein kinase phosphorylates phosphorylase kinase
phosphorylase kinase activates Glycogen phosphorylase
45
What are the 2 phases of glycolysis ?
energy investment
| energy generation
46
What are the steps in the energy investment phase ?
Glucose is phosphorylated by hexakinase to glucose 6 phosphate
this isomerises to fructose 6 phosphate
this is converted to fructose 1,6 bisphosphate by phosphofructokinase
this splits into an equilibrium of dihydorxyacetone phosphate and glyceraldehyde 3 phosphate
47
What are the steps in the energy generation phase ?
glyceraldehyde 3 phosphate changes into 1,3 bisphosphoglycerate
this changes into 3 phosphoglycerate
this then changes into 2 phosphoglycerate
this then turns into phosphoenoylpyruvate in dehydration
this is the turned into pyruvate by pyruvate kinase
48
What is the yield of glycolysis per every molecule of glucose ?
2 pyruvate
2 net ATP
2 G3P
49
Where is glucokinase found ?
in the liver
50
What is the cori cycle for ?
What happens to glucose under anaerobic conditions
51
What are the steps of the cori cycle ?
Glucose 6 phosphate is converted to Pyruvate (glycolysis)
pyruvate is converted to lactate by lactate dehydrogenase
the lactate is taken to the liver
converted back to Pyruvate
made into the glucose in gluconeogenesis
52
The glucose made in the cori cycle can be used for what ?
glycolysis
53
Where does the link reaction happen ?
mitochondrial matrix
54
What conditions does the link reaction happen under ?
Aerobic
55
What is the link reaction ?
pyruvate is converted to acetyl coA in an irreverisble oxidative decarboxylation
catbon dioxide comes off
coA comes in
56
What catalyses the link reaction ?
pyruvate dehydrogenase complex
57
What is also made in the link reaction ?
NADPH - for biosynthesis
58
What is substrate level phosphorylation ?
Direct formation of ATP from the phosphorylation of ADP
59
What is oxidative phosphorylation ?
ATP is formed in the ETC as electrons are transferred from electron carriers to molecular oxygen
60
Where does the TCA cycle occur ?
mitochondrial matrix
61
What are the steps in the TCA cycle ?
```
Acetyl coA condenses with oxaloacetate to form citrate
citrate to isocitrate
isocitrate to alpha-ketoglutarate
alpha- ketoglutarate to succinyl coA
succinyl coA to succinate
succinate to fumarate
fumarate to Malate.
```
62
What are the 3 enzymes in the TCA cycle ?
Citrate synthase
isocitrate dehydrogenase
alpha-ketoglutarate dehydrogenase complex
63
What is also produced in the TCA cycle ?
GDP-GTP-ATP
FAD-FADH2
NAD-NADH
CO2
64
What are the 2 steps of the pentose phosphate pathway ?
irreversible oxidative phase
| reversible non oxidative phase
65
What is the irreversible oxidative phase ?
glucose 6 P combines with water and 2x NADP
| makes ribulose 5 phosphate carbon dioxide and 2xNADPH
66
What catalyses the irreversible oxidative phase ?
glucose 6 phosphate dehydrogenase
67
Where does the pentose phosphate pathway occur ?
cytosol
liver
adrenal cortex
mammary glands
68
What is the reversible non oxidative phase ?
ribulose 5 phosphate can be turned into Glyceraldehyde 3 phosphate
Ribose phosphate to make nucleic acids
fructose 6 phosphate which can isomerise back to glucose 6 phosphate
69
Where does the pyruvate in gluconeogenesis come from ?
lactate
| alanine
70
What are the steps in gluconeogenesis ?
```
2 x pyruvate
2 x Oxaloacetate
2 x phosphoenoylpyruvate
equlibrium of dihydroxyacetone phosphate and glyceraldehyde 3 phosphate
fructose 1,6 bisphosphate
furctose 6 phosphate
glucose 6 phosphate
glucose
```
71
What enzymes are involved in gluconeogenesis ?
pyruvate carboxylase
PEP carboxykinase
Fructose 1,6 bisphosphotase
glucose 6 phosphatase
72
What do amino acids consist of ?
carbon skeletons - ketoacids
| to which an amino group can be attached
73
What is transamination ?
the formation of one amino acid from another by transfer of an alpha amino group
74
Which enzymes catalyse transamination ?
aminotransferase
75
Where are aminotransferase enzymes found ?
in the cytosol and the mitochondria
76
What do aminotransferase enzymes catalyse specifically ?
transfer of an alpha amino group to an alpha ketoacid
77
What does transamiantion require ?
vitamin b6 - pyridoxine
78
How is glutamate made via transamination ?
from alpha ketoglutarate which receives an alpha amino group to become glutamate
79
How can aspartate be made from glutamate ?
glutamate transfers its alpha amino group to become alpha ketoglutarate
the group is recived by oxaolacetate (a ketoacid) which becomes aspartate
80
How are aminotransferases subject to product feedback inhibition ?
high amounts of aspartate (the product) can turn off the enzyme
81
As the demand for amino acids increases what can happen ?
enzyme induction in the liver as demand for specific amino acids increases
82
How is tyrosine made ?
from the essential amino acid phenylalanine by
| phenylalanine hydrolase
83
What does a build up of phenyalanine lead to ?
formation of phenyl ketones
leads to CNS damage
can saturate transporters in the blood brain barrier so that other molecules cant enter the brain
84
what are the consequences of phenylketonuria ?
they have to stop protein break down and therefore require high energy foods (fat/sugar)
85
How can phenylketonuria occur ?
no phenylalanine hydrolase - tyrosine cant be made and therefore phenylalanine builds up
86
Which amino acids are described as being glucogenic ?
amino acid that end up as TCA cycle intermediates - they ultimately end up as oxaloacetate
87
Which amino acids are described as being ketogenic ?
amino acids that become intermediates in ketogenesis (acetoacetate production)
88
What does it mean to be solely ketogenic ?
they make acetoacetate only
89
what does 3 phosphoglycerate turn into ?
pyruvate via glycolysis
90
What does pyruvate get converted into ?
acetyl coA
91
what does acetylcoA get converted into ?
acetoacetate - a ketone body
92
Which amino acids are purely ketogenic ?
leucine
lysine
tryptophan
they enter at acetoacetate
93
How is ammonia formed ?
protein turnover
inactivation of neurotransmitters
exercise
protein brekadown
94
Why must ammonia be removed from the tissues ?
it is toxic
95
How is ammonia removed from cells ?
it is converted to urea in the liver
| removed from cells that cant make urea
96
How is ammonia removed from the brain ?
alpha ketoglutarate is converted to glutamate by glutamate dehydrogenase
this uses up one ammoium ion
the glutamate is then converted to glutamine by glutamine synthase - this used another ammonium ion
this is taken to liver where glutamine is converted back to glutamate by glutaminase , this releases another ammonium ion
the second ion is removed via oxidative deamination
97
How is ammonia removed from the muscles ?
alpha ketoglutarate is converted to glutamate using an ammonium ion and glutamate dehydrogenase
glutamate is transaminated to alanine using pyruvate
alanine is taken to the liver
in the liver alanine is converted back to glutamate
98
Which enzyme catalyses the conversion of glutamate tioalanine via transamination ?
alanine amino transferase
99
What is oxidative deamination ?
glutamate is converted alpha ketoglutarate via glutamate dehydrogenase to release another ammonium ion
100
What happens to the ammonium ions released in the liver ?
they enter the urea cycle
101
What happens in the urea cycle ?
toxic ammonia is converted to the urea in the liver
102
For every molecule of urea how many ammonium ions are removed ?
2
103
What is citrulline ?
it is formed when carbamoyl phosphate combines with ornithine
104
How is ornithine formed ?
arginase catalyses the reaction by which arginine is converted into ornithine releasing urea
105
Where does the urea cycle happen ?
in the liver
| partly in cytosol and partly in mitochondria
106
What happens in the urea cycle ?
carbon dioxide and ammonium combine to form carbamoyl phosphate - this is catalysed by carbamoyl phosphate synthase
carbamoyl phosphate is transferred to ornithine to form citrulline
exits mitochondria on a carrier
citrulline and aspartate combine to make arginosuccinate
arginosuccinate is converted to arginine relasing fumarate
arginate is converted to ornothine again by arginase which releases the urea
107
What is the rate limiting step in the urea cycle ?
carbon dioxide + ammonium to give carbamoyl phosphate catalysed by carbamoyl phosphate synthase
108
What is the source of aspartate ?
the fumarate released from the conversion of arginosuccinate to arginine
fumarate is converted to malate
malate is oxidised to oxaoloacetate
oxaloacetate is transaminated to form aspartate using glutamate.
109
What happens in the lipolysis of triglycerides ?
triglycerides are converted into fatty acids and glycerol by lipase
110
What happens to the glycerol ?
it is taken to the liver where
glycerol is phosphorylated to glycerol phosphate by glycerol kinase
glycerol phosphate is converted to dihydroxyacetone phosphate
this splits into an equilibrium with glyceraldehyde 3 phosphate
glyceraldehyde 3 phosphate is converted to glucose in gluconeogenesis
111
What happens during the activation of fatty acids ?
fatty acids + coA gives fatty acyl coA
| catalysed by fatty acyl coA synthase
112
How is fatty acyl coA transported into the mitochondria ?
the CAT shuttle
113
What is the CAT shuttle ?
acyl coA changes into coA
at the same time acyl carnitine is made from carnitine
acyl carnitine is taken into the mitochondria on a translocase carrier
acyl carnitine becomes carnitine as the coA becomes acyl coA for oxidation
114
Describe beta oxidation of fatty acetyl coA ?
acetyl coA is oxidised to transenoyl coA
transenoyl coA is hydrated to betahydroxyacyl coA
this is oxidised to betaketoacylcoA
this is thiolysed into acetyl coA and an acycl CoA which is now 2 carbons shorter
115
Where does beta oxidation take place ?
mitochondria
116
Describe ketogenesis ?
acetyl coA is compressed with another molecule of acetyl coA to make acetoacetyl coA
this is converted to HMG-coA via HMG-coA synthase
this is converted back to acetyl coA and acetoacetate is given off and this turns into B-hydroxybutarate.
117
What is the first step in fatty acid synthesis ?
transport from the mitochondria into the cytosol
118
How is citrate transported into the cytosol ?
citrate breaks down into acetylcoA and oxaloacetate
acetylcoA is used for fatty acid synthesis
oxaloacetate breaks into malate
malate is made into pyruvate
pyruvate enters the mitochondria
pyruvate turns into oxaloacetate
this turns back into cirate
119
What happens in the activation of acetyl coA ?
acetyl coA is converted into malonyl coA via acetyl coA carboxylase using carbon dioxide
120
What is fatty acid synthase ?
it is a dimer of acyl carrier proteins
| they accept malonyl coA and acetyl coA when the coA is released
121
What are the 4 steps of reaction in adding 2 carbon units ?
condensation
reduction
dehydration
condensation
122
What happens in condensation ?
the malonyl ACP and the acetyl ACP combine to form acetoacyl ACP which is 2C
123
7 cycles of these reactions leads to what being formed ?
16 acyl chain - palmitate when cleaved off the ACP
124
How many ATP are produced in the oxidation of palmitoyl coA ?
```
there are 7 cycles of Beta oxidation
this makes 7 FADH2 7NADH and 8 acetyl coA
each NADH makes 2.5 ATP
Each FADH2 makes 1.5 ATP
in the TCA cycle - 7.5 ATP
1.5 ATP
1 ATP
multiply by 8 - 108 ATP
```
125
What is the yield of one round of the TCA cycle ?
1 FADH2
3 NADH
1 GTP
126
What is the yield of one beta oxidation ?
1 FADH2
1 NADH
1 acetyl co A - at the end get 2 as they both are acetyl coA
127
How are unsaturated fatty acids made ?
elongation beyond 16 carbons requires oxidases which introduce double bonds
128
What is cholesterol ?
a 27 carbon steroid molecule made from acetyl coA
129
How is cholesterol synthesised ?
formation og HMG by HMG coA reductase
| HMG is converted to squalene which is made into cholesterol
130
What stimulates HMG-coA Reductase ?
high insulin: glucagon as phosphorylation inactivates the enzyme
131
How are fatty acids transported
by being attached to albumin
132
How are triglycerides transported ?
lipoproteins
133
how is cholesterol transported ?
lipoproteins
134
What does a lipoprotein do ?
```
phospholipid bilayer
unesterified cholesterol
esterified cholesterol
hydrophobic core
apo proteins
```
135
What chylomicrons do ?
transport triglycerides from ingested fats to the rest of the body
136
What do chylomicrons contain ?
triglyceride
cholesterol
apo protein B48
137
What is the action of chylomicrons ?
they steal Apo protein CII and Apo protein E from HDL
this activates lipoprotein lipase in the endothelial surface of vasculature
hydrolyses the triglycerides
138
What happens to the chylomicrons when the triglycerides have been depleted ?
they return the apo protein CII to HDL
139
What happens to the Apo B48 and Apo E ?
they return to the liver for degradation
140
What do VDL and IDL do ?
transport lipids from the liver to the rest of the body
141
Where are VDL and IDL made ?
hepatocytes
142
What do VLDL and IDL contain ?
triglycerides
cholesterol
Apo 100
143
What do VLDL and IDL do when released into circulation ?
steal apo CII and Apo E from HDL
| allows lipoprotein lipase to hydrolyse the triglycerides
144
What happens as the TAG is removed from the VDL ?
the apo CII is returned to HDL
| VLDL becomes IDL
145
What do IDL remnants do ?
go back the the liver
146
What happens to IDL remaining in circulation ?
receives cholesterol from HDL
| donates phospholipids and TAG to HDL
147
What does LDL do ?
transports cholesterol to peripheral tissues
148
What does Apo E do ?
binds to LDL receptors on peripheral cell
LDL enters the cell by endocytosis
in the cell LDL fuses with lysosomes - cholesterol released
149
Where is HDL made ?
in the liver
150
What does HDL contain ?
phospholipid and Apo proteins
151
What does HDL do ?
accepts free cholesterol from the peripheral cells
| passes it onto VLDL./IDL to become LDL
152
What are the other roles of HDL ?
source of apo proteins for chylomicrons and VLDL
| can carry cholesterol back to the liver
153
What are genetic dyslipidameias ?
elevated blood triglyceride or cholesterol due to abnormal lipid metabolism
could be due to faulty lipoprotein lipase
154
What is the hormonal response to a food deficit ?
```
blood glucsoe decreases
so insulin decreases
glucagon decreases
noradrenlaine increases
cortisol increases
overall - insulin:glucagon decreases
```
155
What food stores are metabolised for energy ?
glycogen
adipose tissue
muscle amino acids
156
What is the mechansim for topping up blood glucose between meals ?
blood glucose decreases
glucagon/ noradrenaline decrease
liver glycogenolysis - glucose released into the blood
157
What does the release of glucagon and noradrenaline do to key enzymes ?
glycogen synthase is inhibited
| glycogen phosphorylase activated
158
How long do liver glycogen stores last ?
12 hours
159
What happens to top up blood glucose after ?
gluconeogenesis
muscle amino acids are transmaminated to alanine
this goes to the liver
alanine is transaminated back to pyruvate
this is converted to glucose in gluconeogenesis
160
How is alanine converted to pyruvate ?
transamination
alanine donated alpha amino group to alpha ketoglutarate - become glutamate
the alanine becomes pyruvate
the glutamate can be used in the removal of ammonia in the urea cycle
161
What does glucagon do to key enzymes ?
pyruvate kinase is inhibited - glycolysis inhibited
| Fructose 1,6 BPase is stimulated - gluconeogenesis
162
What does acetyl coA do to key enzymes ?
inhibits pyruvate dehydrogenase complex - stop production of more acetyl coA
pyruvate carboxylase activated by acetyl coA - gluconeogenesis
163
What is the consequence of using ,muscle amino acids for gluconeogenesis ?
decreased protein synthesis
| increased production of urea in urea cycle
164
After depletion of liver glycogen how much protein and urea is lost daily ?
12-14 g N
| 80g of protein
165
What activates lipase ?
a decrease in insulin
166
What does lipase do ?
lipolysis - break down of lipids to fatty acids and glycerol
167
What can glycerol be used for ?
gluconeogenesis
168
What happens to the fatty acids ?
they can undergo Beta oxidation in the liver or the muscle to make acetyl coA
169
What is the consequence of rapid fat break down ?
not enough oxaloacetate to combine with acetyl coA to enter the TCA cycle
acetyl coA is redirected to ketogenesis in the HMG-coA cycle - in the liver
170
How long after initial food deficit are ketone bodies produced ?
3 days
171
What can ketone bodies be used for ?
they are a source of fuel for brain and cardiac muscle
| enzyme induction occurs in the brain and cardiac muscle - utilise the ketone bodies for energy
172
What is adaptation ?
when the brain can get 50% of its energy frome ketone bodies and there isnt a need fro glucose
173
What does adaptation include ?
```
no requirement for glucose
rate of gluconeogenesis decreases
less amino acids sued
decreased nitrogen loss
less than 5g a day loss
```
174
In trauma how is information conducted to the brain ?
baroreceptors
pain receptors
sensory receptors
175
What happens once trauma is detected by the brain ?
There is a change in the hormone profile -
glucagon , NA and cortisol are increased
reduced insulin to glucagon ratio
176
What is starvation ?
hypoglycaemia
increased ketogenesis
small protein losses when adapted
177
What is trauma ?
Hyperglycaemia due to increased cori cycle activity
blunted ketone body formation
marked protein loss - no adaptation
178
Why is their hyperglycaemia in trauma ?
insulin resistance due to high levels of catabolic hormones
increased cori cycle activity
increased gluconeogenesis due to raised glucagon and cortisol
179
Describe the cori cycle ?
```
glucose 6 phosphate
converted to pyruvate
converted to lactate
taken to the liver
made into pyruvate
glucose via gluconeogenesis
the glucose cant et in due to the high insulin resistance - contributes to hyperglycaemia
```
180
Why is their marked protein loss in trauma ?
increased protein loss because less ketone bodies to use as fuel
181
What fuels the immune system in trauma ?
glutamine
reduced rate of protein synthesis
increased cytokine activity results in catabolism
182
What are the traits of DM ?
hyperglycaemia and ketoacidosis
183
What does insulin promote in a non-diabetic ?
GLUT-4 transporter which transports glucose into cells
| this promotes glycogenesis
184
Why does blood glucose increase due to DM ?
blood glucose increases due to more catabolic hormones
cells are deficient in glucose because no GLUT-4
glycogenolysis and gluconeogenesis occur
185
What happens to amino acids in DM ?
the amino acids are lost from the muscle to fuel gluconeogenesis
insulin would have uptaken it for anabolic reactions
186
What does decreased insulin mean ?
lipase is active
| high rate of lipolysis and therefore high amount of fatty acids in the blood
187
What happnes to the fatty acids ?
they are oxidised in the muscle or the liver
by beta oxidation to form acetyl coA
the acetly coA can also be used to mske ketone bodies
188
What happens in a non diabetic to control lipolysis ?
acetoacetate - a ketone body stimulates insulin which will turn lipase off
189
Why does lipolysis continue in diabetics ?
there is no insulin for acetoacetate to stimulate hence lipase remains active and lipolysis will continue
190
What is the diabetic diet ?
low in sugars and fat
| high in fibre , fruit and veg
191
What is the diabetic diet associated with ?
low rates of dental caries
192
What can type 2 diabetes lead to an increased risk of ?
periodontal disease
193
How is fructose metabolised ?
the slow muscle route - Glucose 6 phosphate isomerising to fructose 6 phosphate and then fructose 1,6 BP which splits into the equilibrium of DHAP and G3P
the fast hepatic route - fructose is phosphorylated by hepatic fructokinase into fructose 1 phosphate and then converted unto DHAP by fructose 1 phosphate aldolase
194
What is fructosuria ?
absence of hepatic fructokinase
this mean the hepatic fast route cant be taken for fructose metabolism
instead the slow muscle route is taken and this leads to a build up of fructose in the blood which spills into the urine
195
What us hereditary fructose intolerance ?
absence of fructose 1 phosphate aldolase
the fructose 1 phosphate cant be converted to DHAP
inorganic phosphate is trapped
phosphate is needed to phosphorylate glycogen phosphorylase and fructose 1,6 BPase
this means glycogenolysis and gluconeogenesis cant occur
results in hypoglycaemia
196
What are the sources of fructose ?
sucrose
avoid anything with sucrose
people with HFI have a low sugar diet - therefreo good DMFT
