Clinical Genetics And Biochemistry Flashcards
(239 cards)
1
Q
What is a transposon and how much of the human genome is made up of transposon repeats?
A
A mobile genetic element. 45% of human genome
2
Q
Are transposons well or poorly conserved?
A
Poorly conserved
3
Q
What are piRNAs?
A
Piwi protein interacting RNAs which control transposon activity. They are an example of non-coding RNA
4
Q
What is heterochromatin and how much of the human genome is made up of it?
A
Tightly packed repetitive DNA with little or no active gene expression. Stains darkly with giemsa stain. Makes up 6.7% of the human genome.
5
Q
What is euchromatin?
A
Loosely packed DNA with lots of active gene expression. Pale staining with giemsa.
6
Q
What is chromatin?
A
DNA and histones
7
Q
What makes up 3 - 4% of the human genome?
A
Non coding mRNA genes
8
Q
Is heterochromatin well or poorly conserved?
A
Poorly conserved
9
Q
What does non coding RNA do?
A
It regulates the expression of protein coding mRNA genes
10
Q
Give examples of non-coding RNA
A
PiRNA and microRNA. PiRNA regulates transposon activity. MicroRNAs can silence protein coding mRNA or stop translation
11
Q
What makes up 1.2% of the human genome?
A
Protein coding mRNA gene
12
Q
Are RNA genes well or poorly conserved?
A
Well conserved
13
Q
What are the three types of mutations?
A
Pathogenic
Non-pathogenic (polymorphism)
Conferring disease susceptibility (risk allele)
14
Q
What is a polymorphism?
A
Non-pathogenic mutation
15
Q
What are the 5 types of disease causing mutations in DNA and chromosomes?
A
SNPs (single nucleotide polymorphism aka point mutation)
Indels (small insertions or deletions)
CNV (copy number variants, large indels)
Microsatellites (dynamic) (expansion or contraction of tandemly repeated DNA)
Minisatellite (expansion or contraction of tandemly repeated DNA)
16
Q
Which disease causing mutations are associated with repetitive DNA?
A
CNV
Microsatellites
Minisatellites
17
Q
What is a SNP?
A
Single nucleotide polymorphism. It is pathogenic if it changes the open reading frame or is found in the promoter or regulatory region as this will change the amount of mRNA produced.
18
Q
What is an indel?
A
Small insertions or deletions. SNP indel = 1 nucleotide inserted or deleted. Micro indel = more than 1 nucleotide inserted/deleted
19
Q
What is a CNV?
A
Large indel, duplication or inversion
20
Q
What are micro and mini satellites and which of them is dynamic?
A
Contractions or expansions of tandemly repeated DNA. Microsatellites are dynamic.
21
Q
What is a Barr body?
A
Chromatin of an inactive X chromosome. It is seen as a blob of condensed chromatin at the edge of the nucleus of a cell in interphase.
22
Q
What is a manifesting heterozygote?
A
A female carrier of an X linked recessive condition who shows some symptoms due to skewed X inactivation
23
Q
What does hemizygous mean?
A
A boy with one affected X chromosome in an X linked recessive condition
24
Q
What is a true homozygote?
A
Have inherited 2 copies of the same mutation (usually due to consanguineous mating)
25
What is a compound heterozygote?
Inherited 2 different mutations but has phenotype of homozygote (most homozygotes are actually compound heterozygotes, unless consanguineous mating is involved)
26
What is consanguineous mating?
1st cousin mating
27
What is a dynamic mutation?
The mutation increases in length between the parent and the child e.g. Microsatellites
28
What is genomic imprinting? Give an example
Where expression of an allele is dependent on its parental origin e.g. Paternal 15q12 deletion causes Prader-Willi syndrome in boys. Maternal 15q12 deletion causes angelman syndrome in girls.
29
7 Location of mutations in protein coding genes
```
Enhancer
Promoter
Start codon
Exon donor consensus
Exon acceptor consensus
Stop codon
Poly A tail
```
30
8 Location of mutations in protein coding genes
```
Enhancer
Promoter
Start codon
Intron donor consensus
Intron acceptor consensus
Within an exon
Stop codon
Poly A addition signal
```
31
What is the point of the untranslated region of a gene?
It is where microRNAs look for sequences to regulate gene expression
32
What happens if there is a mutation in the enhancer or promoter region of a gene?
There will be an increase or decrease in gene product
33
What happens if there is a mutation at the start codon?
No translation of abnormal translation
34
What happens if there is a mutation at the intron donor consensus (beginning of intron) or intron acceptor consensus (end of intron)?
Incorrect splicing
35
What is an intron?
Non coding section of a gene
36
What is an exon?
Coding section of a gene
37
What happens if there is a mutation in the stop codon?
Translation will not be stopped and the protein will get bigger
38
What happens if there is a mutation in the poly A addition signal?
mRNA will not be polyadenylated resulting in less stable mRNA and hence less protein
39
What is the poly A tail added to?
It is added to mRNA to increase its stability
40
What effects can a mutation have on a protein?
Loss of function (little/no protein produced or faulty protein produced)
Gain of function (harmful product or enhanced function or new function)
Dominant negative (mutant protein interferes with function of wild type protein e.g. Mutation in one collage oligomer will disrupt the whole collagen structure)
41
What is snRNA?
Small nuclear RNA. It is involved in splicing.
42
What can mutations in miRNA cause?
Autosomal deafness
| EDICT (eye disease)
43
What can mutations in snRNA cause?
MOPD type 1 which is a type of primordial dwarfism
44
What is long ncRNA?
Long non coding RNA (>200 bp)
45
What do mutations in long ncRNA cause?
Aplastic anaemia
46
What is a SNP RFLP?
Restriction fragment length polymorphism. Gain/loss of a restriction site.
47
What is a transition?
SNP which results in a purine to purine change (A to G) or a pyrimidine to pyrimidine change (T to C)
48
What is a purine
Adenine and guanine
49
What is a pyrimidine
Cytosine and thymine
50
Which bases bind together?
A binds T
| G binds C
51
What is a transversion
Where a SNP results in a purine (A or G) being swapped for a pyrimidine (C or T) or vice versa
52
What is a synonymous SNP?
Silent mutation (amino acid remains the same)
53
What is a non-synonymous SNP?
Results in a different amino acid with very different properties from the original one
54
What is a Missense mutation?
Changes in the coding sequence result in one amino acid being swapped for another. Can be conservative or non-conservative.
55
What is a conservative Missense mutation?
Changes in the coding sequence result in an amino acid change. The new amino acid has similar properties to the old one.
56
What is a non-conservative Missense mutation?
Changes in the coding sequence result in a change in amino acid, the new amino acid does not have similar properties to the old one
57
What does a SNP indel cause?
A frameshift mutation, since it inserts/deletes 1 nucleotide (ie not a multiple of 3).
58
What causes a frameshift mutation?
Inserting/deleting a number of nucleotides which is not a multiple of 3
59
What is a nonsense mutation?
It causes insertion of a premature stop codon
60
What are the 3 methods of detecting SNPs?
Restriction digest followed by gel electrophoresis (SNP RFLP only)
ARMS (primers)
Microarray
61
Glycogenesis
Glycogen formation from glucose
62
Glycogenolysis
Glycogen breakdown to form glucose and glucose-6-phosphate
63
Gluconeogenesis
Production of glucose from other metabolic pathways (especially glucose from pyruvate)
64
What is glycolysis?
Anaerobic conversion of glucose to pyruvate
65
What are the products of glycolysis?
Net 2 ATP
2 pyruvate
2 NADH
66
What are the 3 stages of glycolysis?
Glucose to fructose-1-6-bisphosphate
DHAP to glutaraldehyde
Glutaraldehyde to pyruvate (occurs twice)
67
How many carbon atoms in pyruvate?
3
68
Where and how is glycolysis controlled?
At the formation of glucose-6-phosphate
At the formation of fructose-1,6-bisphosphate. Phosphofructokinase is regulated by fructose-2,6-bisphosphate. Lots of glucose = lots of fructose-2,6-bisphosphate which activates phosphofructokinase. Vice versa for low glucose.
69
What are the only tissues that have an absolute requirement for blood glucose for metabolism?
Rbc
Brain
70
What energy source can the brain use in starvation?
Ketones from fatty acid breakdown
71
When does most gluconeogenesis occur?
Sleep
72
Where is most glycogen stored?
Mainly in muscle but some in liver
73
Where is glycogen made?
Liver
74
Where is most glycogen stored?
Mainly in muscle but some in liver
75
When does most gluconeogenesis occur?
Sleep
76
What energy source can the brain use in starvation?
Ketones from fatty acid breakdown
77
What are the three steps of glycolysis which have a large negative delta G and are essentially irreversible?
Hexokinase
Phosphofructokinase
Pyruvate kinase
78
What is hexokinase inhibited by?
Glucose-6-phosphate
79
What is phosphofructokinase inhibited by?
Citrate and ATP
80
What is phosphofructokinase activated by?
Fructose-2,6-bisphosphate
| And AMP
81
What is pyruvate kinase inhibited by?
Alanine and ATP
82
What is pyruvate kinase activated by?
Fructose-1,6-bisphosphate
83
What are all steroid hormones synthesised from?
Cholesterol
84
What are 3 classes of steroid hormone?
Corticosteroids (glucocorticoids such as cortisol) (mineralocorticoids such as aldosterone)
Androgens
Estrogens
85
Where does steroid synthesis occur?
Adrenal cortex
Testes
Ovaries
86
Which enzymes are involved in steroid synthesis?
Members of the cytochrome P450 oxidase family
87
Which gene codes for enzymes involved in steroid synthesis?
CYP11
88
What are symptoms of diabetes?
```
Unexplained weight loss
Polyuria
Polydipsia
Blurred vision
Fatigue
Thrush
Slow healing of cuts
Ketone smell on breath due to ketoacidosis
```
89
What is the main difficulty in recognising diabetes symptoms?
Habituation
90
What is the main difference in symptoms between type 1 and type 2 diabetes?
Type 1 symptoms develop quickly
91
Compare insulin and glucagon levels in type 1 diabetes?
Insulin levels are low
| Glucagon levels are high
92
What is the 1st step in diagnosing diabetes?
Glucose in urine test
93
What conditions are associated with type 2 diabetes?
```
Central obesity
High triglycerides
Low HDL cholesterol
High fasting glucose
High blood pressure
```
94
What is impaired glucose tolerance?
More insulin secreted as insulin receptors lose sensitivity
95
How do adipocytes contribute to insulin resistance?
They secrete adipokines which increase insulin resistance and they inhibit secretion of adiponectin which increases insulin sensitivity
96
What acute complications are associated with type 1 diabetes?
Hypoglycaemic coma (too much insulin or insufficient glucose from diet)
Ketoacidosis (coma)
97
What are chronic complications of diabetes?
Retinopathy and cataracts
Neuropathy and nephronopathy caused by diabetic microangiopathy. For type 2 diabetes major causes of death are stroke and peripheral vascular disease.
98
What are the 4 mechanisms of glucose mediated damage?
Production of ROS
Protein kinase C
Non-enzymatic glycation of proteins
Polyol pathway
99
How are blood glucose levels measured?
Using immobilised glucose oxidase which generates hydrogen peroxide which generates a colour change
100
What is HbA 1c?
Haemoglobin A which has been non-enzymatically modified by glycation
101
How does insulin resistance lead to type 2 diabetes?
Overproduction of insulin, high glucose levels and free fatty acid levels damage beta cells. (Beta cells die with age but obesity and insulin resistance increase rate of death)
102
What is meant by an unsaturated fat?
Double bonds in the fatty acids
103
What is a triacylglyceride made up of?
3 fatty acid chains bound to a glycerol by ester linkages
104
Compare fat and glycogen as energy stores?
7 x more energy in 1 gram of fat compared to 1 gram of glycogen because glycogen carries water for hydration. Also triacylglycerols are more reduced so release more energy when oxidised. The body can only store less than one day's worth of glycogen whereas fat stores can meet energy requirements for months
105
Where is fat found in the body?
Under the skin
In the abdominal cavity
Mammary glands
106
What is brown fat?
Fat found in newborns. Contains more mitochondria so appears brown
107
What are adipocytes?
Cells that store large amounts of triacylglycerols as fat droplets
108
What 4 functions does cholesterol have?
It maintains membrane fluidity
It is the precursor for steroid hormones
It is the precursor for bile acids
It is the precursor for vitamin D
109
Where does cholesterol come from
Half is synthesised de novo and half is from the diet
110
Where are the major synthesis sites for cholesterol?
Liver
Intestine
Skin (waterproofing)
111
What is the starting point for cholesterol synthesis?
Acetyl CoA
112
What is the main role of vitamin D?
Calcium homeostasis
113
What is the difference between cholesterol and cholesteryl esters?
Cholesteryl esters are more hydrophobic and cannot be incorporated into membranes
114
What is a PEST sequence?
An amino acid sequence on cell cycle proteins that targets them for rapid degradation
115
Names the types of mutations associated with repetitive dna in order of size
Microsatellites
Minisatellites
Copy number variants
116
What is anticipation?
When a disease gets more severe with each generation (associated with microsatellites which are dynamic)
117
How big are microsatellites?
Less than 100bp
118
Name a disease caused by microsatellites
Huntingtons
119
What techniques can be used to analyse microsatellites?
Southern blots
| Triplet repeat primed pcr
120
How big are minisatellites?
1 - 400kb
121
Name a disease caused by minisatellites
Myoclonus epilepsy. There is a minisatellite repeat in the promoter region of the cystatin b gene
122
What do CNVs arise from?
Low copy repeats
123
Name 3 diseases associated with CNVs
```
Haemophilia A (x linked recessive)
Prader willi (imprinting deletion of 15q12)
Angelman (imprinting deletion of 15q12)
```
124
How are CNVs detected?
CGH microarrays
FISH
Karyotyping
125
Why is colchicine used in karyotyping?
It stops the cell cycle in metaphase
126
Which dye is used in karyotyping?
Giemsa
127
What causes down syndrome?
Trisomy 21
128
What does it mean to be homozygous for a minisatellite or microsatellite?
Same number of repeats
129
What does it mean to be heterozygous for microsatellites and minisatellites?
Different numbers of repeats
130
What is a haplotype?
Alleles which are inherited together
131
Which type of screening is used to test for cystic fibrosis and sickle cell disease?
ASO hybridisation
132
Which tests are used to screen for dystroglycanopathies
Multiplex pcr
| MAPH
133
Where in a cell is glucose-6-phosphate converted to glucose?
ER
133
In which cells is it possible for glucose-6-phosphate to be converted to glucose?
Kidney cortex, beta cells, liver, muscle
133
Why are 5 proteins required to generate glucose from glucose-6-phosphate?
3 transport proteins, 1 glucose-6-phosphatase and 1 stabilising protein
134
In terms of glucose homeostasis what are the anabolic hormones?
Insulin
135
In terms of glucose homeostasis what are the catabolic hormones?
Glucagon, cortisol and catecholamines (adrenaline and noradrenaline)
136
Which cells secrete glucagon?
Alpha cells of the islets of langerhans in the pancreas
137
Which cells secrete insulin?
Beta cells of the islets of langerhans
138
What carries out the exocrine function of the pancreas?
Acini
139
What is the morphological difference between alpha and beta cells?
Alpha cells are larger and found at the periphery of the islets of langerhans
Beta cells are smaller and found at the centre of islets of langerhans
140
What do delta cells of the islets of langerhans secrete?
Somatostatin which inhibits growth hormone
141
What do pp cells of the islets of langerhans secrete?
Pancreatic polypeptide
142
Describe how insulin goes from preproinsulin to insulin?
It is secreted as preproinsulin in the ER where the signal peptide is cleaved to form proinsulin. Then the c peptide is cleaved in the secretory granule to form insulin (same process for glucagon, secreted from preproglucagon)
143
Describe the structure of insulin
Alpha and beta chain held together by 2 disulfide bonds
144
What are the 2 ways insulin can exist?
Monomer
| Hexamer
145
What are triggers for insulin secretion?
Increased blood glucose levels
GI hormones
Glucagon
Parasympathetic stimulation (ACh)
146
Where is insulin stored?
Granules in beta cells in islets of langerhans in the pancreas
147
What happens to insulin when it reaches target cells?
It binds to insulin receptors, gets internalised, dimerises, aggregates, autophosphorylates and phosphorylates effector proteins
148
Which tissues does insulin target?
Liver
Adipose tissue
Muscle
149
What effects does insulin have on the liver?
Stimulates glycolysis, synthesis of glycogen, fatty acids, TAGs, VLDLs. Supresses gluconeogenesis
150
What effect does insulin have on adipose tissue?
Stimulates fatty acid synthesis
| Upregulates glut4 for more glucose uptake
151
What effect does insulin have on muscle cells?
Increases glycogen synthesis
Increases amino acid uptake and protein synthesis
Upregulates GLUT4 for more glucose uptake
152
What is the cause of type 1 diabetes mellitus?
Autoimmune destruction of beta cells
153
What triggers glucagon secretion?
Low blood glucose conc
| Some GI hormones
154
What decreases glucagon secretion?
High blood glucose
High FFA in blood
High insulin
Somatostatin
155
What is the half life of glucagon?
5 minutes
156
In which organs is glucagon degraded?
Liver and kidneys
157
Which tissues does glucagon affect?
Liver and adipose
158
How does glucagon affect the liver?
Stimulates gluconeogenesis
Stimulates breakdown of glycogen
Inhibits glycolysis (inhibiting PFK-1 with citrate and pyruvate kinase with alanine)
Inhibits production of glycogen
Inhibits lipogenesis (inhibition of acetyl coA carboxylase)
159
What effect does glucagon have on adipose tissue?
Stimulates lipolysis (cAMP activation of hormone lipase which converts TAGs to FFA and glycerol, FFA undergo beta oxidation to produce ATP. Glycerol is converted to glucose by gluconeogenesis).
160
Which tissues are affected by adrenaline?
Liver and muscle
161
What affects on glucose homeostasis does adrenaline have?
Similar effects to glucagon. Stimulates gluconeogenesis and inhibits glycogen and fat synthesis
162
Which receptors does adrenaline bind to in the liver?
Alpha receptors
163
Which receptors does adrenaline bind to in muscle?
Beta receptors
164
Where is adrenaline and noradrenaline stored?
Granules in adrenal chromaffin cells
165
What is non-enzymatic glycation of proteins?
Where glucose binds to valine and lysine side chains forming advanced glycation end products. Receptor for advanced glycation end products causes inflammation
166
What is the polyol pathway?
Where glucose is converted to sorbitol by aldose reductase. Sorbitol accumulates in cells that do not possess sorbitol dehydrogenase. Sorbitol accumulation causes cataracts and neuropathy by reducing myo-inositol uptake
167
What are the treatments for type 2 diabetes mellitus?
Acarbose
Metformin
Sulphonylureas
168
What does acarbose do?
Slows breakdown of carbohydrates in the gut by inhibiting alpha glucosidase
169
How does metformin work?
Affects insulin signalling and sensitivity
170
How do sulfonylureas work?
Increase sensitivity of beta cells to glucose to increase insulin synthesis
171
What are the steps in cortisol production?
Cholesterol to pregnenolone to cortisol
172
Which enzyme converts cholesterol to pregnenolone?
Desmolase
173
Which enzyme converts pregnenolone to cortisol?
A cytochrome p450 oxidase
174
Where is cortisol produced?
The zona fasciculata of the adrenal cortex
175
What is cortisol bound to in the blood?
Corticosteroid binding globulin or albumin
176
How does cortisol affect the immune system?
Decreases circulating leukocytes and impairs b cell and t cell response
177
What 6 things does cortisol affect?
```
Metabolism
Central nervous system
Immune system
Cardiovascular system
Connective tissue
Bone and calcium metabolism
```
178
What is cortisol's affect on the central nervous system?
Increased appetite
Decreased libido
Insomnia
179
What effect does cortisol have on connective tissue?
Inhibits fibroblasts leading to loss of collagen, thinning of skin and easy bruising
180
How does cortisol affect the cardiovascular system?
Increases cardiac output
181
How does cortisol affect bone and calcium metabolism?
Inhibits bone formation
Decreases calcium uptake from the gut
Increases parathyroid release
182
What is also secreted with ACTH?
MSH
183
How do pyrimidine and purine de novo synthesis differ?
Pyrimidine the ring is built and added onto activated ribose. Purine the ring is built onto activated ribose
184
What is the starting point for pyrimidine synthesis?
Carbomoyl phosphate
185
How is de novo pyrimidine synthesis regulated?
ATCase is allosterically inhibited by CTP
186
How is oritidylate converted into UMP?
Decarboxylation
187
How is UTP converted to CTP?
Amidation
188
How is dUMP converted to dTMP?
Methylation - this step is blocked by anticancer drugs
189
What is needed for the salvage pathway for purines?
APRT
| HPRT
190
What is lesch-nyhan syndrome?
Loss of HPRT activity so loss of salvage pathway for purines. Mental deficiencies and self destructive behaviour
191
What is the defect in severe combined immunodeficiency?
ADA deficiency.
192
What are the treatments for SCID?
Bone marrow transplant
PEGylated ADA injection
Gene therapy
193
How does allopurinol treat gout?
It inhibits xanthine oxidase which is an enzyme in uric acid production from purines
194
How is glycerol converted to glucose in gluconeogenesis?
Glycerol kinase converts it to glycerol 3 phosphate. Which is then converted to DHAP which is then converted to glucose
195
Why is glutamine required for nucleotide synthesis?
Provides NH4 for amidation of UTP to CTP in pyrimidine synthesis.
Provides NH4 for amidation of activated ribose in the first step of purine synthesis to form 5-phosphoribosyl-1-amine
196
How are ribonucleotides converted to deoxyribonucleotides?
Reduction using NADPH and catalysed by ribonucleotide reductase
197
Which enzyme is used in the salvage pathway for pyrimidines?
Phosphoribosyl transferase
198
What happens to triacylglycerols in the lumen of the intestine?
They are hydrolysed by lipases to fatty acids and monoacylglycerols which diffuse into mucosal cells
199
In terms of dietary fat digestion what happens in mucosal cells?
Monoacylglycerols and fatty acids are converted to TAGs again and are packages into chylomicrons with cholesterol and apolipoprotein c-11. Chylomicrons then move into the lymph and blood
200
What happens to chylomicrons in capillaries?
Apo c-11 activates lipoprotein lipases which hydrolyse TAGs to fatty acids and glycerol. Glycerol goes to the liver for glycolysis or gluconeogenesis. Fatty acids either go to the muscle for beta oxidation or adipose tissue for storage
201
How are fatty acids transported in the blood?
Bound to albumin
202
Where does beta oxidation take place?
Mitochondria or peroxisomes
203
How are substances activated for fatty acid degradation/synthesis?
Attached to carrier protein
204
What is the carrier protein for fatty acid degradation?
Coenzyme A
205
What is the carrier protein for fatty acid synthesis?
ACP
206
What is the product of fatty acid activation?
Acyl coA
207
Which enzyme carries out fatty acid activation?
Acyl coA synthetase
208
Where does fatty acid oxidation occur?
Mitochondrial membrane
209
What is used to transport acyl coA into mitochondria?
Carnitine
210
What does carnitine acyltransferase I do?
Attaches acyl coA to carnitine
211
What does carnitine acyltransferase II do?
Recycles carntine out of the mitochondrial matrix
212
What is the end product of beta oxidation?
An acyl coA which is 2 carbons shorter and acetyl coA
213
How many steps in beta oxidation?
4
214
What occurs in step 1 of mitochondrial beta oxidation?
Oxidation catalysed by acyl coA dehydrogenase. FADH2 is formed
215
What are the 4 steps of mitochondrial beta oxidation?
Oxidation
Hydration
Oxidation
Cleavage
216
What happens to acetyl CoA formed in beta oxidation?
It enters the citric acid cycle where is it converted to water and carbon dioxide. The electrons formed are used in oxidative phosphorylation to form ATP
217
What is MCAD deficiency
Medium chain acyl dehydrogenase deficiency. Cannot breakdown acyl coA chains of lengths C6 - C12
218
What are the symptoms of MCAD deficiency?
Fat accumulation in the liver
Low blood glucose levels
High blood octanic acid levels
High concs of C6 - C12 carboxylic acids in urine
219
When is beta oxidation in peroxisomes used?
For very long chain fatty acids
220
What is the inheritance of MCAD?
Autosomal recessive
221
How is beta oxidation in peroxisomes different to beta oxidation in mitochondria?
In peroxisomes hydrogen peroxide is made in the first step rather than FADH2. Hydrogen peroxide is immediately broken down by catalase. No ATP is produced, only heat.
222
What is x linked adrenoleukodystrophy?
Lack of transporters for v long chain fatty acids = accumulation of v long chain fatty acids in blood and death
223
What is zellweger syndrome?
Lack of peroxisomes = v long chain fatty acids in blood = death
224
What are the fates of acetyl coA?
Citric acid cycle
Forms ketone bodies in the liver when oxaloacetate is consumed in Gluconeogenesis
Used for fatty acid and cholesterol synthesis
225
Where are ketone bodies formed?
Liver
226
Name some ketone bodies?
Acetone
Acetoacetate
D-3-hydroxybutyrate
227
What is the affect of ketone body formation?
Ketoacidoisis and coma due to decrease in blood pH
| Ketone smell on breath
228
Where does fatty acid synthesis take place?
Cytoplasm of liver cells and adipocytes
229
How is acetyl coA transported from the mitochondrial matrix to the cytoplasm for fatty acid synthesis?
Via citrate
230
What is the first committed step (irreversible) in fatty acid synthesis?
Acetyl coA is converted to malonyl coA. Catalysed by acetyl coA carboxylase and requires ATP
231
Which enzyme produces acetyl-CoA and malonyl coA?
Transacyclase
232
What is the role of desatuare?
Adds double bonds to fatty acids
233
Which enzymes are used in cholesteryl ester synthesis?
Acyl coA cholesterol acyl transferase
234
What is used to treat high cholesterol?
Resins and statins
235
How do statins work?
They are competitive inhibitors of HMG-coA reductase, they increase the number of LDL receptors, they stabilise atherosclerotic plaques, they are anti-inflammatory, they improve endothelium
236
What is the enterohepatic cycle?
Bile salts are reabsorbed in the small intestine and returned to the liver by the hepatic portal vein where they returned to circulation
237
What do resins do?
Prevent reabsorption of bile salts in the intestine and hence inhibit the enterohepatic cycle. Also increase LDL receptors
