Liver - metabolism Flashcards
(142 cards)
1
Q
which enzyme converts glucose to glycogen?
A
glycogen synthase
2
Q
In which organs does AMP-activated protein kinase phosphorylate key enzymes?
A
liver, heart, muscle, adipose tissue
3
Q
what are the effects of AMP-activated kinase phosphorylating key enzymes?
A
AMP = signal of low energy state
increase in energy providing pathways
inhibit anabolic/ synthetic pathways
4
Q
does glucagon stimulate or inhibit glycogen breakdown and how?
A
stimulates by phosphorylation of a protein that activate glycogen phosphorylase
5
Q
which enzyme converts acetyl CoA to malonyl CoA?
A
acetyl coA carboxylase
6
Q
what stimulates acteyl coA carboxylase?
A
insulin (high insulin levels –> store fats)
7
Q
Which 3 compounds inhibit the conversion of acetyl coA to malonyl coA?
A
AMPK, glucagon, adrenaline
8
Q
when are carbohydrates converted to fatty acids?
A
excess carbohydrates
9
Q
where does fatty acid and lipid synthesis occur?
A
mainly in the liver
also in adipose tissue
breast tissue during lactation to decrease the strain on the body
10
Q
where does the link reaction take place?
A
mitochondria
11
Q
what is pyruvate converted into in anaerobic conditions?
A
lactate
12
Q
which compound from the krebs cycle is converted into acetyl CoA in the cytoplasm?
A
citrate
13
Q
where does fatty acid synthesis take place in the cell?
A
cytoplasm
14
Q
what is the key control point for fatty acid synthesis?
A
acteyl coA carboxylase (acetyl coA –> malonyl coA)
15
Q
what are fatty acids combined with to form triacylglycerols?
A
glycerol 3-phosphate
16
Q
how is acetyl coA converted into malonyl coA?
A
ATP and CO2 required
enzyme = acetyl coA carboxylase
17
Q
which enzyme combines C4 chains with more malonyl coa?
A
fatty acid synthase
18
Q
how many carbons in palmitate?
A
16
19
Q
where are fatty acids modified and stored?
A
endoplasmic reticulum
20
Q
where are triacyclglyerides made?
A
endoplasmic reticulum
21
Q
what happens to lipids in adipose tissue?
A
stored in cytosol
22
Q
what happens to lipids in the liver?
A
packaged into VLDLs –> blood –> adipose tissue for storage or peripheral tissue for energy
23
Q
which happens to lipids in peripheral tissues?
A
used as an energy source
24
Q
what are the 2 steps involved in fatty acid metabolism?
A
- carrier needed to transport fatty acyl CoA from cytosol into matrix
- B oxidation
25
where does B oxidation of fatty acids occur?
mitochondrial matrix of liver hepatocytes
26
which fatty acids can diffuse across the cell membrane without a carrier?
those with fewer than 12C chains
27
what products are produced from fatty acid metabolism?
ATP, NADH, FADH, acetyl coA
28
which cofactors are involved in B oxidation and what happens to them?
FAD and NAD get reduced to FADH and NADH
29
how are fatty acids activated before they are transported across the cell membrane?
ATP required to activate them to fatty acyl coA
30
what controls fatty acid oxidation?
the transport of fatty acids across cell membranes by carnitine carriers
31
when is breakdown of fatty acids inhibited?
when high levels of malonyl coA (signalling high energy state)
high levels inhibit acyl-transferase -1 so fatty acids are not transferred to carnitine carriers
32
which enzyme is required for fatty acid synthesis?
acetyl coA carboxylase
33
overall how many ATP molecules are produced per palmitoyl coA molecule?
108
34
what is produced with each turn of b oxidation?
1 acetyl coA (NADH, FADH)
35
Is fatty acid oxidation aerobic or anaerobic and why?
aerobic because NADH and FADH are oxidised by the krebs cycle etc. which are aerobic processes
36
when does ketone body formation occur?
excess acetyl coA for example when the body breaks down fats for energy when fasting or in uncontrolled diabetes
37
why can acetyl coA not be metabolised via the krebs cycle?
starvation state so krebs cycle intermediates are depleted
38
what are the steps in ketone body formation?
2 acteyl coA --> acetoacetyl coA --> HMGcoA --> acetoacetate --> acetone and 3-hydroxybutyrate
39
where does ketone body formation occur?
mitochondria of liver cells
40
what are the 3 ketone bodies?
acetoacetate, acetone, 3-hydroxybutyrate
41
which organ can use ketone bodies for energy?
brain oxidises ketone bodies for energy
42
what is cholesterol used for?
component of cell membranes
| synthesis of hormones, bile, vitamin D etc
43
what are the 2 sources of cholesterol?
```
from the diet (egg yolk, liver, meat)
and synthesis (75%)
```
44
where is cholesterol synthesised?
in almost all tissues but mainly the liver
| to some extent in the small intestine
45
how do plant sterols and stanols helps to lower plasma cholesterol levels?
they inhibit cholesterol uptake from the gut
46
how many stages are there to cholesterol biosynthesis?
4
47
which is the most important step?
1st stage
48
where do statins inhibit cholesterol synthesis?
inhibit HMG coA reductase enzyme
49
what is required for cholesterol synthesis?
ATP
50
what happens during the 1st stage of cholesterol synthesis?
acetyl coA --> mevalonate (C6)
51
what happens during the second stage of cholesterol synthesis?
mevalonate --> phosphorylated isoprene units (C5) = activation
52
what happens in the 3rd stage of cholesterol synthesis?
6 isoprene units polymerised --> C30 chain (squalene)
53
what happens in the final stage of cholesterol synthesis?
cyclisation --> ring structure (lanosterol) --> cholesterol
54
which 3 compounds are isoprenoids?
isopentylpyrophosphate
geranylpyrophosphate
farnesylpyrophosphate
55
what is prenylation?
adding a farnesyl or geranyl lipid chain that anchors the small G protein to the intracellular face of the lipid membrane
56
which isoprenoid produces Ras small GTPase?
FPP - farnesylpyrophosphate
57
which isoprenoid produces Rho small GTPase?
GGPP - geranylgeranylpyrophosphate
58
what do Ras and Rho affect?
cell signalling functions
| gene expression
59
what are the pleiotropic effects of statins?
antioxidant properties
inhibit inflammatory responses
stabilise atherosclerotic plaques
improve endothelial dysfunction
60
how is the rate of cholesterol synthesis controlled?
controlling ACTIVITY or AMOUNT of HMG-coA reductase
61
what happens to the activity of HMG-CoA reductase when energy levels are low?
glucagon inhibits phosphorylation of the enzyme so inhibits synthesis
62
which 2 factors control the activity or amount of HMG-coA reductase?
energy levels and cholesterol levels
63
how do energy levels effect cholesterol synthesis?
alter the activity of HMG-coA reductase
64
how do high cholesterol levels inhibit the synthesis of cholesterol?
alter the amount of HMG-coA reductase present
inhibit trasncription
stimulate degredation
65
why do high energy levels increase cholesterol synthesis?
insulin stimulates phosphoylation of HMG-CoA reductase
66
how does insulin affect the amount of HMG-coA reductase present?
stimulates transcription of the enzyme
67
how does cholesterol effect SREBP?
high levels of cholesterol inhibit the release of SREBP from the ER, which binds to sterol response unit of gene coding for HMG-coA reductase and is therefore required for its synthesis
68
how is cholesterol removed from the body?
cannot be broken down so can only be excreted
| secreted in bile --> excreted in faeces
69
which 3 common diseases are linked with excess cholesterol?
coronary heart disease
steatohepatitis
alzheimers disease
70
how are mono- and poly-unsaturated fats beneficial?
reduce CHD risk and may have other benefits
71
why are saturated fats bad?
they increase the levels of LDL cholesterol in the blood
72
How do trans fats affects lipoprotein levels?
increase the levels of LDLs and reduce the levels of HDLs
73
what effect does dietary cholesterol have on lipoproteins?
can raise LDL levels but has less effect than others
74
how is cholesterol transported in the blood?
insoluble therefore transported by lipoproteins
75
what are the 4 types of lipoprotein and what are their roles?
Chylomicrons: dietary fats (cholesterol and triglycerides) transported from intestines to liver
VLDLs: lipids made in liver transported from liver to peripheral tissues
LDLs: main cholesterol carrier in blood for peripheral tissues
HDLS: cholesterol from peripheral tissues to liver (reverse cholesterol transport)
76
what is the significance of apolipoproteins?
specific protein embedded in surface of lipoproteins determine start and end points for cholesterol transport
77
which apolipoproteins do HDLs have?
Apo A-I and Apo A-II
78
which apolipoproteins do LDLs have?
Apo B and Apo E
79
how are LDLs taken up into cells?
LDL receptor binds Apo B-100 or Apo E
endocytosis of LDL and receptor
LDL released and LDL receptor recycled
80
how is LDL receptor activity controlled?
high levels of cholesterol inhibit synthesis of LDL receptor so reduced expression of LDL receptors on cell surface so more LDLs circulating in blood
81
how can HDLs protect against atherosclerosis?
scavenges cholesterol from cells and LDLs and transports it to the liver
82
why do HDLs not cause atherosclerosis?
APo A apolipoproteins are resistant to oxidation
83
how do LDLs contribute to atheroclerosis?
oxidised LDLs = very inflammatory and atherogenic
| xs cholesterol deposited in arteries
84
which phospholipid does cholesterol form a raft with in membranes?
sphingolipids --> reduce membrane fluidity
85
what is Tangier disease?
lack of HDL --> at risk of CHD
86
What is familial hypercholesteraemia?
lack of LDL receptors
| mutations affecting LDL receptor or defective apo B100 so impaired binding of LDL
87
how is high cholesterol linked to alzheimers disease?
APOE4 allele --> increased risk
increased plasma cholesterol correlates with increased risk
accumulation of AB peptide in animal models
statin therapy and decreased alzheimers?
88
what is non-alcoholic steatohepatitis?
form of chronic liver disease
accumulation of triglycerides
associated with obesity and metabolic syndrome, use of some drugs, inherited metabolic disorders
insulin resistance --> increased insulin secretion --> stimulates fatty acid synthesis
89
how does fat accumulation in the liver affect the tissue?
leads to inflammation and fibrosis
90
what occurs in alcoholic steatohepatitis?
metabolism of high amounts of alcohol --> large amounts of NADH
fatty acid oxidation inhibited and excess triglyeride synthesis activated
91
why might non-alcoholic steatohepatitis occur?
insulin resistance, obesity, metabolic disorders
92
how do LDLs enter the subintimal space beneath the endothelium of blood vessels?
damage to endothelial cells from smoking or high blood pressure enables them to enter
93
how do LDLs become foam cells?
oxidised LDLs engulfed by macrophages --> foam cells
94
what is found within an atherosclerotic necrotic core?
cholesterol and necrotic cells damage
95
in which layer do athersclerotic plaques form?
tunica intima
96
what components form the fibrous cap of a plaque?
collagen and smooth muscle fibres
97
which components make the necrotic core prothrombotic?
collagen (I, III) --> GPVI on platelets
LPA --> P2Y on platelets
TF --> FVIII --> activates coagulation
98
how do macrophages assist in the degredation of the fibrous plaque cap?
secrete proteinase enzymes that degrade the cap
99
why does steatohepatitis occur?
impaired energy metabolism
| triglyercide export from liver is impaired --> accumulation of lipid droplets in hepatocytes
100
what does the surface layer of lipoproteins consist of?
phospholipids and free cholesterol
101
what does the hydrophobic core of lipoproteins consist of?
triglyceride and cholesterol esters
102
what carrier is required to convert glucose-1-phosphate into glycogen?
UDP --> UDP-glucose
103
what is the primer called that is required to build glycogen?
glycogenin
104
where are the 1-6 bonds in the glycogen molecule?
at the branch sites
105
where are the 1-4 glycosidic bonds in the molecule?
within the straight chains
106
what are the advantages of glycogen as a storage molecule?
can be broken down quickly and can be built quickly
107
which tissues store glycogen?
all to limited extent mainly the liver and skeletal muscle
108
why is glycogen stored in the liver?
stored until early fasting when it is broken down to release glucose for the body
109
why is glycogen stored in muscles?
to be broken down for muscle energy use
110
what is the control point of glycogen synthesis?
glycogen synthase
prevents synthesis/ use occurring simultaneously
glycogen synthase and glycogen phosphorylase are reciprocally controlled
111
what is the term for glycogen breakdown?
glycogenolysis
112
what does glycogen phosphorylase do?
removes glucose units from glycogen
113
what do additional enzymes do to break up glycogen?
remove branches
114
is ATP required to breakdown glycogen?
no, nor UDP
115
in which tissues can glucose-6-phosphate be broken down into glucose?
liver (and kidneys to some extent)
| not muscle as don't have the enzyme to convert glucose-6-phosphate into glucose
116
in which tissues in glycogen broken down?
liver, kidneys to some extent
117
what is 'hitting the wall'?
depletion of glycogen supplies
| slow adaptation to using fatty acids as oxygen supply
118
what is the energy supply for the final sprint in a marathon race?
glycogen
119
what happens when glycogen is depleted?
exhausation and collapse
120
what adaptation do muscles need for marathon running?
increase number of mitochondria
| increase storage of glycogen
121
why is a defect in glycogen synthesis fatal?
muscle cramps and weakness
122
what are the 2 phases of glycolysis?
preparative
| generative
123
which is produced by the preparative phase of glycolysis?
fructose 1,6 bisphosphate
124
what are the products of glycolysis?
ATP, NADH, pyruvate, water
125
what is the importance of phosphorylating glucose?
glucose is then unable to exit the cell and more glucose can enter along the concentration gradient
126
at which 2 points in glycolysis is ATP required?
glucose --> glucose-6-phosphate
| fructose-6-phosphate to fructose 1-6-bisphosphate
127
why is anaerobic glycolysis important?
enables cardiac myocytes to generate ATP in the absence of oxygen (short term survival of anoxic muscle)
128
which organ metabolises lactate?
liver
129
how many ATP molecules are produced per glucose in anaerobic glycolysis?
2
130
how does the liver use lactate?
lactate --> pyruvate --> gluconeogenesis
131
at which 2 points in glycolysis is ATP produced?
1,3-bisphosphoglycerate --> 3-phosphoglycerate
| phosphoenolpyruvate --> pyruvate
132
which step in glycolysis requires NAD?
glyceraldehyde 3-phosphate --> 1,3-bisphosphoglyerate
133
how are fructose and galactose metabolised?
broken down into compounds that enter glycolysis
134
is fructose and galactose metabolism under hormonal control?
no only glucosse
135
name 2 rare but life threatening inherited disorders with absence of enzymes from the pathways that metabolise sugars
hereditary fructose intolerance (1: 20,000 births)
| galactosaemia (1: 23000 births)
136
what are the 4 possible fates of glucose?
used to produce ATP for energy
conversion to glycogen for storage
synthesis of other cellular components
xs --> fatty acid synthesis --> storage
137
which organ relies on glucose for energy?
brain
138
what level should blood glucose be maintained at?
around 5mM
139
at what level can hypoglycaemia cause confusion and coma?
140
what happens if blood glucose increases above 8mM?
protein glycation --> long term vascular damage
141
what is excess anaerobic glycolysis indicative of and why?
tumours because they absorb glucose more rapidly and use anaerobic respiration
142
which scan shows up rapid glucose uptake and glycolysis?
PET scans
