IMMS revised Flashcards

1
Q

What is the structure of DNA? (coiling)

A

double helix
coils around nucleosomes and coils again into supercoils
then into chromosomes

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2
Q

What are the 4 DNA bases and their pairing?

A

Adenine binds to thymine (2 H bonds)
Guanine binds to cytosine (3 H bonds)

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3
Q

How many chromosomes are there?

A

46
22 pairs then sex chromosomes

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4
Q

Structure of chromosomes

A

Long arm (q)
Short arm (p)
Centromere controls movement at division
Telomere seals tip
Each chromosome contains hundreds of genes

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5
Q

What stains can be used to see chromosomes?

A

Giemsa: G banding
Quinacrine: Q banding

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6
Q

What does mitosis do?

A

Producing two daughter cells genetically identical to parent cell
Growth
Replace dead cells

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7
Q

What are the stages of the cell cycle?

A

G1
S phase
G2
Mitosis

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8
Q

Are mitotically inactive cells in the cell cycle?

A

No
They are in G0

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9
Q

What happens in interphase?

A

Cell grows
Replication of cytoplasmic organelles and DNA

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10
Q

When in the cell cycle does DNA replication occur?

A

S phase

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11
Q

What happens in prophase?

A

Chromatin condenses into chromosomes
Centrosomes nucleate microtubles and move to opposite poles of nucleus

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12
Q

What happens in prometaphase?

A

Nuclear membrane breaks down
Microtubules invade nuclear space
Chromatids attach to microtubules

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13
Q

What happens in metaphase?

A

Chromosomes line up along equatorial plane (metaphase plate)

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14
Q

What happens in anaphase?

A

Sister chromatids separate and are pushed to opposite poles of the cell

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15
Q

What happens in telophase?

A

Nuclear membranes reform
Chromosomes unfold into chromatin
Cytokinesis begins

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16
Q

Why is mitosis clinically relevant?

A

Categorising tumours as benign or malignant
Detecting chromosomal abnormalities
Grading malignant tumours

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17
Q

What does meiosis produce?

A

4 genetically different daughter cells
2 divisions

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18
Q

Where can mitosis and meiosis occur?

A

Mitosis can occur in all cells
Meiosis can only happen in gametes

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19
Q

How are sperm produced?

A

Primordial germ cells undergo mitoses to produce spermatogonia
Meiotic divisions commence at puberty
cytoplasm divides evenly
After meiosis II four equal gametes
Millions of mature sperm continuously produced

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20
Q

How long does sperm production take?

A

60-65 days

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21
Q

How are ova produced?

A

Primordial germ cell undergoes mitosis in utero to produce oogonia
First meiotic division in utero
Process suspended until ovulation in future
Second meiotic division only at fertilisation

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22
Q

Does the cytoplasm divide equally in ova?

A

No
1 egg and 3 polar bodies that apoptose

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23
Q

What is non-dysjunction?

A

Failure of chromosome pairs to separate in Meiosis I or sister chromatids to separate properly in meiosis II

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24
Q

What is trisomy 21?

A

Downs syndrome

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25
What is gonadal mosaicism?
Occurs when precursor germline cells to ova or spermatozoa are a mixture of two or more genetically different cell lines One cell line is normal, the other mutated Increasing risk with advancing paternal age Parent is healthy, but the fetus may have a genetic disease
26
What does genotype mean?
genetic constitution of an individual
27
What does phenotype mean?
Appearance of an individual that results from the interaction of the environment and genotype
28
What does allele mean?
One of several alternative forms of a gene at a specific locus
29
What do homozygous and heterozygous mean?
Homo: alleles at locus the same Hetero: alleles at locus different
30
What does hemizygous mean?
only one copy of a gene rather than the usual two copies e.g. men on an X chromosome
31
What is a rare disease?
Affects 1 in 2000 people
32
Signs of rare disease
Group of congenital abnormalities Extreme presentation of common conditions Neurodevelopmental delay or degeneration early Extreme pathology
33
What is the karyotype for a girl with Edwards syndrome?
47, XX, +18
34
What is the karyotype for a girl with Downs?
47, XX, +21
35
What is the karyotype for a girl with Patau?
47, XX, +13
36
What is the karyotype for Turners?
45, X
37
What is translocation?
A type of chromosome mutation where part of one chromosome is transferred to another part of the same chromosome or a different one
38
What can deletion of 5p cause?
Cri du chat
39
What can a deletion of 15q cause?
Prader Willi Angelman
40
What is FISH?
Fluorescence in situ hybridisation Probe labelled with fluorochrome Separate DNA Hybridize probes onto DNA
41
How does microarray work?
Probe DNA Add to slide Look under fluorescent microscope at colour ratios
42
What are constitutional abnormalities?
Occur at gametogenesis and affect most all in body Heritable
43
What are acquired abnormalities?
Changes occur during lifetime Malignant changes in malignant tissue Not heritable
44
How can cytogenetics help in acquired abnormalities?
Confirm malignancy Classification of disease Prognosis Monitoring
45
What is gene deregulation?
Juxtaposition of genes to a regulating gene Alters regulation Can result in increased transcription
46
What are fusion/hybrid genes?
Breakpoints occur within 2 genes Genes fuse and give rise to a hybrid gene
47
What are multifactorial conditions?
Diseases that are due to a combination of genetic and environmental factors
48
What is heritability?
The proportion of the aetiology that can be ascribed to genetic factors as opposed to environmental factors
49
Characteristics of multifactorial inheritance
incidence of the condition is greatest amongst relatives of the most severely affected patients risk is greatest for the first degree relatives and decreases rapidly in more distant relatives If there is more than one affected close relative then the risks for other relatives are increased
50
What do genome wide association studies do?
compare the frequency of markers in a sample of patients and a sample of healthy controls Look for markers that is seen more frequently in the disease population Sequence that area to try to identify the gene and allele associated with the increased likelihood of developing the condition
51
What environmental agents can affect embryogenesis?
Drugs and Chemicals Maternal Infections Physical agents Maternal Illness
52
What are some examples of simple molecules?
Sugars Lipids Amino acids
53
What are some examples of macromolecules?
Haemoglobin DNA Glycogen Rhodopsin Collagen
54
What are the different types of carbohydrate?
Monosaccharide Disaccharides Oligosaccharides Polysaccharides
55
What are some sugar derivatives?
Aminosugars e.g. glucosamine Alcohol-sugars e.g. sorbitol Phosphorylated e.g. glucose-6-phosphate Sulphated e.g. heparin
56
What bond holds amino acids in proteins together?
Peptide
57
What are the 2 types of glycosidic bonds and where are they found?
OH, O-glycosidic in di-,poly- and oligosaccharides NH, N-glycosidic in DNA and nucleotides
58
What are oligosaccharides?
contain 3-12 monosaccharides Products of digestion of polysaccharides, or part of complex protein/lipids
59
What is the structure of a disaccharide?
contain 2 monosaccharides joined by an O-glycosidic bond
60
What are polysaccharides + 2 examples?
Formed by thousands of monosaccharides joined by glycosidic bonds E.g. starch, glycogen
61
What are proteoglycans?
long, unbranched polysaccharides radiating from a core protein
62
What is the structure of lipids?
Straight C chains (mostly 16-20) with a methyl group and a carboxyl group at the ends Ester bonds
63
What makes up a nucleotide?
nucleotide sugar (ribose/deoxyribose) phosphate group
64
What is the structure of amino acids?
Building blocks of proteins (20 different) C with amine group, carboxyl group and side chain (R) Charge determined by all 3, changes with the pH of the environment Side chain often determines polarity
65
What makes up a nucleoside?
Nitrogenous base Sugar Joined in N-glycosidic bond
66
Properties of peptide bonds
Very stable Cleaved by proteolytic enzymes Partial double-bond Flexibility around C atoms not involved in bond, allows multiple conformations. Usually one preferred native conformation, determined mainly by the type of side chains
67
What is a protein?
A protein is a large polypeptide, usually from a few 10s to 1000s aminoacids Huge variety of functions arises from huge number of different 3D shapes
68
What forces can keep the shape of proteins?
Van der Waals forces Hydrogen Bonds Hydrophobic Forces Ionic bonds Disulphide bonds
69
What are van der waals forces?
Weak attractive interactions between atoms due to fluctuating electrical charges important when two macromolecular surfaces fit closely in shape
70
What are H bonds?
Interaction between dipoles, involving an hydrogen and an oxygen/nitrogen/fluorine Allow weak interactions with other chains
71
What are ionic bonds?
Occur between fully or partially charged groups. Weakened in aqueous systems by shielding by water molecules and other ions in solution
72
What is the primary structure of proteins?
Linear sequence of aa linked by peptide bonds
73
What is the β pleated sheet?
Formed by H-bonds between linear regions of polypeptide chains 2 or more segments of a polypeptide chain line up next to each other, forming a sheet-like structure held together by hydrogen bonds Can be parallel or antiparallel
74
What makes up the secondary structure of a protein?
α helix and β pleated sheet
75
What is the α helix?
The carbonyl (C=O) of one amino acid is hydrogen bonded to the amino H (N-H) of an amino acid that is four down the chain Pulls the polypeptide chain into a helical structure R groups free to interact
76
What is the tertiary structure of a protein?
overall 3D conformation of the protein Forces involved include electrostatic, hydrophobicity, H-bonds, and covalent bonds
77
What is the quaternary structure of a protein?
Three dimensional structure of a protein composed of multiple subunits E.g. haemoglobin and DNA polymerase
78
What is sickle cell anaemia?
a genetic disorder that is characterized by the formation of hard, sticky, sickle-shaped red blood cells, in contrast to the biconcave-shaped red blood cells
79
What is the structure of haemoglobin?
Tetramer of 2 identical dimers Each dimer is 1 alpha and 1 beta chain four heme groups surrounding a globin group, forming a tetrahedral structure
80
What is euchromatin?
Actively transcribing cellular DNA light staining
81
What is heterochromatin?
Transcripitionally inactive cellular DNA Dense staining often adjacent to nuclear membrane Highly condensed
82
Which bases are purines and pyramidines?
Purine: A & G, 2 rings Pyramidine: T, C, U, 1 ring
83
What is the immunoglobulin structure?
2 identical small (light) + 2 identical large (heavy) polypeptide Chains joined by disulphide bonds Both light and heavy regions contain variable and constant regions V regions interact to produce single antigen binding site at each branch
84
What does antiparallel mean for DNA?
The two strands of DNA run in opposite directions On one strand the 5 C of the sugar is above the 3 C, so this strand runs in the 5' to 3' direction Other, 3' above 5' so runs 3' to 5' direction
85
Process of DNA replication
- DNA helicase disrupts binding to open into replication fork - Leading strand runs 3' to 5', lagging is 5' to 3' - RNA primer bonds to leading at 3' end - Leading strand replicated by polymerases, continuous - Lagging strand binds with multiple primers, polymerase adds DNA (okazaki fragments), discontinuous - When both strands formed, exonuclease removes primers and replace with bases - DNA Ligase joins lagging strand up - Telomerase catalyses synthesis of new telomeres at ends
86
What is the structure of the DNA double helix?
Purine bonded to pyrimidine so equidistant Stacked bases stabilised by Van der Waals and hydrophobic effects Phosphate groups on outside, 3rd -OH on phosphate is free and dissociates a H+ at physiological pH, so DNA -ve charge Contains major and minor grooves where bases can interact with other molecules
87
Which enzymes and proteins work to open and unwind DNA?
Helicase opens it Single stranded binding proteins keep it open Topoisomerase unwinds supercoil
88
Function of DNA
Template and regulator from transcription and protein synthesis Structural basis of heredity and genetic disease
89
What is the P53 protein?
Transcription factor that regulates cell cycle and apoptosis Halts replication in cells that have suffered DNA damage Loss of both p53 alleles common in tumours
90
What does DNA polymerase do?
synthesize DNA only in the 5′ to 3′ direction needs a primer to initiate synthesis
91
What is the structure or a eukaryotic ribosome?
80S split into 60S and 40S subunits 60S subunit contains 5S, 28S and 5.8S rRNAs complexed with proteins 4OS contains 18S
92
What is the structure of a prokaryotic ribosome?
70S split into 50S and 30S subunits
93
What does DNA helicase do?
hydrolyses ATP to break bonds and unwind DNA double helix
94
What does DNA primase do?
synthesises a small RNA primer, which acts as a ‘kick-starter’ for DNA polymerase
95
What does DNA topoisomerase do?
Uncoils DNA
96
What is the leading strand in DNA replication?
The newly formed strand from DNA polymerase In a 5' to 3' direction
97
What does DNA ligase do?
Joins okazaki fragments to form lagging strand of DNA
98
What are the 3 stages of DNA replication?
Initiation Elongation Termination
99
What happens during initiation of DNA replication?
DNA helicase unwinds DNA Replication begins at replication fork DNA primase synthesises an RNA primer for DNA polymerase to attach
100
What happens during elongation in DNA replication?
DNA polymerase adds free nucleotides to the 3' end of the primer (reads 3-5, synthesises 5-3) Creates new strand running 5' to 3' which becomes leading strand RNA primers added to other template strand (lagging) and DNA polymerase synthesises in fragments (okazaki)
101
What happens in termination in DNA replication?
Either when two rep forks meet or no more template to synthesize RNAase H removes primers from lagging and DNA ligase joins all the fragments to create a strand New strands are bound and synthesised
102
What does DNA nuclease do in replication?
catalyze the cleavage of phosphodiester bonds
103
What is a DNA substitution?
when one or more bases in the sequence is replaced by the same number of bases
104
What is a DNA deletion?
when a base is deleted from the sequence
105
What's the difference between DNA and RNA?
RNA is single stranded (can sometimes helix with itself) DNA is present in cells at all time, many mRNA species only accumulate following cell stimulation RNA chains are shorter RNA contains a ribose sugar RNA contains uracil not thymine RNA is more resistant to UV damage
106
What is insertion in DNA mutations?
when a base is added to the sequence.
107
What is a point mutation in DNA?
a change in one base in the DNA sequence
108
What does tRNA do?
tRNA carry amino acids to ribosomes, and check that they are incorporated in the right poistion
109
What is the structure of mRNA?
long, single-stranded molecule consisting of nucleotides attached by phosphodiester bonds 4 nitrogenous bases: A,U,G,C
110
What are the stages of DNA transcription?
Initiation Elongation Termination
111
Which enzyme catalyses transcription?
RNA polymerase
112
What happens in initiation of transcription?
RNA polymerase attaches to and moves along the DNA molecule until it recognises a promoter sequence (may be multiple promoter sequences within a DNA molecule) Transcription factors bind to the promoter sequences with RNA polymerase. RNA polymerase unwinds a portion of the DNA exposing bases on both sides
113
What happens in elongation of transcription?
Template strand is read in a 3′ to 5′ direction, other DNA strand is the coding strand. RNA polymerase uses incoming ribonucleotides to form the new mRNA and catalyses the formation of phosphodiester bonds between adjacent ribonucleotides Bases can only be added to the 3′ end, so the strand elongates in a 5’ to 3’ direction.
114
What happens in termination of transcription?
Elongation continues until the RNA polymerase encounters a stop sequence. RNA polymerase releases the DNA template Mature mRNA made
115
Where does translation take place?
In the cytoplasm
116
What are some features of the genetic code?
- Degenerate but unambiguous: many AA specified by more than one codon, but each codon specifies only one AA - Universal - Non-overlapping and without punctuation: codons do not overlap and each nucleotide is only read once
117
What is translation?
The process by which the genetic code contained within a mRNA molecule is decoded to produce a specific sequence of amino acids in a polypeptide chain.
118
What are the key components needed for translation?
mRNA, ribosomes, and transfer RNA
119
Where are the anticodon and AA on the tRNA?
Every tRNA molecule possesses an anticodon that is complementary to the mRNA codon, and at the opposite end lies the attached amino acid
120
What is the process of translation?
start codon (5’AUG) is recognised At 5’ cap of mRNA, 40s subunit of the ribosome binds larger 60s subunit binds to complete the initiation complex tRNA binds to A site of ribosome, adds AA and leaves ribosome translocates down mRNA polypeptide growing at P site stop codon
121
What is the purpose of mRNA splicing?
allows the genetic sequence of a single pre-mRNA to code for many different proteins, conserving genetic material
122
What is changed in mRNA splicing?
Removal of introns (non-coding sequences) Joining together of exons (coding sequence)
123
What happens during pre-translational mRNA processing?
5′ Capping Polyadenylation Splicing
124
How is gene expression initiated?
Transcription factors at promoter region. Transcription complex forms at TATA box Helix opens, DNA strands separate RNA polymerase II starts building mRNA
125
What factors turn off gene expression?
Activation of repressors (inhibitors of RNA polymerase binding) Each step of RNA transcription or processing finds no longer actively produced transcription and processing proteins. Complexes do not form anymore for lack of phosphorylation. Enzymes no longer activated RNA stability
126
What is Mendel's law of dominance?
Every gene has 2 alleles that code for a trait. In heterozygotes, one allele is dominant meaning it will always show, one is recessive and is masked by the dominant allele
127
What is Mendel's law of segregation/separation?
Allele pairs separate/segregate randomly from each other during meiosis – each cell has a single allele for each trait
128
What is Mendel's law of independent assortment?
Traits are transmitted to offspring independently of one another
129
What is Mendelian inheritance?
Autosomal and sex-linked Dominant and recessive
130
What is non-Mendelian inheritance?
Imprinting Mitochondrial inheritance Multifactorial Mosaicism
131
What are the categories of genetic disorders?
Chromosome abnormalities Single gene disorders Multi-factorial and polygenic disorders
132
What is an autosome?
Any chromosome, other than the sex chromosomes (X or Y), that occurs in pairs in diploid cells
133
What is an allele?
One or more alternative forms of a gene at a given location (locus)
134
What does homozygous mean?
Presence of identical alleles at a given locus
135
What does heterozygous mean?
Presence of two different alleles at a given locus
136
What does allelic heterogeneity mean?
different mutations within the same gene result in the same clinical condition e.g. cystic fibrosis an individual with an autosomal recessive condition may be a compound heterozygote for two different mutations
137
What does autosomal recessive mean?
Disease manifest in the homozygous state
138
What are the typical features of an autosomal recessive condition?
Male and females affected in equal proportions Affected individuals only in a single generation Parents can be related, i.e. consanguineous
139
What are some examples of autosomal recessive conditions?
Haemochromatosis Sickle cell CF
140
What is the most common gene for CF mutation?
F508 Approx 80% of cases
141
What does autosomal dominance mean?
Disease manifest in the heterozygous state
142
What are some typical features of autosomal dominance?
Male and females affected in equal proportions Affected individuals in multiple generations Transmission by individuals of both sexes, to both sexes
143
What does penetrance mean in genetics?
% of individuals with a specific genotype showing the expected phenotype
144
What does expressivity mean?
Refers to the range of phenotypes expressed by a specific genotype
145
What does anticipation mean in genetics?
genetic disorder affects successive generations earlier or more severely, usually due to expansion of unstable triplet repeat sequences Example – Myotonic Dystrophy
146
What does somatic mosaicism mean?
Genetic fault present in only some tissues in body
147
What does gonadal/germline mosaicism mean?
Genetic fault present in gonadal tissue
148
What does late-onset mean?
Condition not manifest at birth, classically adult-onset
149
What does sex-linked mean?
Condition inherited in AD pattern that seems to affect one sex more than another Example – BRCA1/2
150
What does lyonization mean?
X inactivation Usually only in one of 2 in women
151
What is the disorder in prada-willi?
deletion of paternal genes absence of active paternal genes – maternal uniparental disomy
152
What is the disorder in angelman?
loss of function of maternal UBE3A due to point mutation or deletion paternal uniparental disomy
153
What does homoplasmy mean?
a eukaryotic cell whose copies of mitochondrial DNA are all identical normal healthy tissue
154
What does heteroplasmy mean?
there are multiple copies of mitochondrial DNA in each cell level of heteroplasmy can vary between cells in the same tissue or organ, from organ to organ within the same person, and between individuals in the same family
155
What causes mitochondrial genetic disorders?
mutations in the mitochondrial DNA (15%) mutations in nuclear genes, whose gene products are imported into the mitochondria
156
What does an out of frame deletion do?
Clearly disrupts protein Deletion not a multiple of 3
157
What does an in frame deletion do?
Whole codon deleted AA missing
158
What happens with a non-sense DNA mutation?
Change codon to stop Out of frame deletion produces a stop codon either at deletion site or further along RNA detaches from the ribosome and is eliminated
159
What's a mis-sense varient?
Single base substitution Changes the type of amino acid in the protein May or may not be pathogenic
160
What does locus heterogeneity mean?
Variants in different genes give the same clinical condition
161
What does allele heterogeneity mean?
Lots of different variants in one gene e.g. cystic fibrosis
162
What happens with a gain of function disorder?
Increased gene dosage Increased protein activity
163
What is a loss of function disorder in genetics?
Only one allele functioning
164
What are dominant negative variants in genetic mutation?
Where the protein from the variant allele interferes with the protein from the normal allele
165
What is predictive testing?
Testing healthy at-risk family members for a previously identified familial variant – often dominant
166
What is pre-natal testing?
Genetic test performed in pregnancy where there is a increased risk of a specific condition affecting the fetus Chorionic villous sample or amniocentesis
167
What are the roles of genetic testing?
To confirm a clinical diagnosis To give information about prognosis To inform management Allow pre-symptomatic/predictive testing in close relatives Carrier testing To give accurate recurrence risks Prenatal diagnosis
168
What does Sanger sequencing do?
Uses PCR to amplify regions of interest followed by sequencing of products Useful for single gene testing
169
Downsides of Sanger sequencing?
Slow Expensive
170
Positives of Sanger sequencing?
Very accurate The gold standard
171
What does next gen sequencing allow?
allows rapid sequencing of targeted gene panels generates millions of short DNA fragments fast low cost per gene
172
What does anabolic mean?
synthesise larger molecules from smaller components
173
What does catabolic mean?
break down larger into smaller molecules provides energy
174
What are the 4 pathways for metabolism?
Biosynthesis Fuel storage Oxidative Waste disposal
175
Are biosyntheis and fuel storage anabolic or catabolic?
Anabolic
176
Are oxidation and waste disposal anabolic or catabolic?
Catabolic
177
What are the 3 main dietary energy sources?
Carbohydrates Lipids Proteins
178
What happens to excess energy intake?
Store as triglycerides in adipose (approx 15kg) Store as glycogen (up to 200g in liver & 150g in muscle), 80g in the liver after overnight fast Store as protein in muscle (approx 6kg).
179
How much energy per gram of carb and protein?
4kcal
180
How much energy per gram of lipid?
9kcal
181
How much energy per gram of alcohol?
7kcal
182
What is basal metabolic rate?
A measure of the energy required to maintain non-exercise bodily functions
183
What are some functions included in BMR?
respiration, contraction of the heart muscle, biosynthetic processes, repairing & regenerating tissues, ion gradients across cell membranes
184
What are the conditions for measuring BMR?
Post-absorptive (12 hour fast) Lying still at physical and mental rest Thermo-neutral environment (27 – 29oC) No tea/coffee/nicotine/alcohol in previous 12 hours No heavy physical activity previous day Establish steady-state (~ 30 minutes)
185
What factors can decrease BMR?
Age (old) Gender (female) Dieting/Starvation Hypothyroidism Decreased muscle mass
186
What factors increase BMR?
Body weight (BMI) (higher) Hyperthyroidism Low ambient temp. Fever/infection/chronic disease
187
What intake does the NHS recommend for BMR?
25-35 kCal/kg/day for patients who are not severely ill or injured, nor at risk of re-feeding syndrome
188
How much glucose does the brain require?
150g of glucose a day
189
After an overnight fast, how much glycogen does the liver have?
80g glycogen
190
What happens during an overnight fast?
Insulin decrease Glycogenolysis
191
What happens after a few days of starvation?
Insulin low Cortisol increases Gluconeogenesis: from glycerol, AA and lactate
192
What happens after 4 days of starvation?
Liver makes ketones from fatty acids Brain adapts BMR decreases
193
What is the recommended alcohol intake?
not to regularly drink more than 14 units of alcohol a week
194
What is the recommended protein intake?
0.8g/kg/day protein
195
What is recommended saturated fat intake?
Men: 30g Women: 20g a day
196
What is homeostasis?
maintenance of a constant internal environment
197
What is autocrine communication?
Cells talking to themselves messenger molecules bind with receptors in the cell where they are produced
198
What is paracrine communication?
Cells talking to neighbour cells Signal diffuses across gap between cells Inactivated locally, so doesn’t enter the blood stream
199
What is endocrine communication?
Cells talking to cells elsewhere in the body Hormones
200
Examples of paracrine communication
Interleukins Platelet derived growth factor
201
What is a hormone?
Molecule that act as a chemical messenger
202
Structure of peptide hormones
Made of amino acids Vary in size from few amino acids to small proteins Some have carbohydrate side chains (glycoproteins) Hydrophillic (like water)
203
How fast are peptide and steroid hormone responses produced?
Peptides fast Steroids slow
204
What do ribosomes do?
Translate mRNA into protein
205
What does the golgi apparatus do?
Mediates protein sorting to specific sites
206
What happens in the mitochondria?
TCA cycle Oxidative phosphorylation
207
What happens at the sER?
No ribosomes Site of lipid synthesis Some drug metabolism
208
What happens at the rER?
Studded with ribosomes Site of protein synthesis
209
What do the cell microtubules do?
Give structure to cell
210
What makes up the phospholipid bilayer?
Phospholipids (hydrophillic head, hydrophobic tail inwards) Cholesterol Proteins (extrinsic and intrinsic) Glycoproteins
211
What is the structure of phospholipids?
Phosphate head: charged, hydrophillic Fatty acid tail: non-polar, hydrophobic
212
What can freely move through the phospholipid bilayer?
Water (aquaporins) Gases (CO2, N2, O2) Small uncharged polar molecules
213
What is the phospholipid bilayer impermeable to?
Ions (Na+, K+, Cl-, Ca2+ etc.) Charged Polar molecules (ATP, Glucose-6-phosphate) Large uncharged polar molecules (Glucose)
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What uses simple diffusion to get across membranes?
Blood gases, water Urea, free fatty acids Ketone bodies
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What uses facilitated diffusion to get across membranes?
Glucose (hexose sugars) GLUT family
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What uses primary active transport to get across membranes?
Ions (Na+, K+, Ca2+, H+, HCO3-) Water-soluble vitamins
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What uses secondary active transport to get across membranes?
Glucose (hexose sugars) Symporters (Na+ + X)
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What does the membrane potential mean?
Potential difference across the cell membrane generated by differential ion concentrations of key ions K+ major determinant
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What plays a major role in K+ homeostasis?
Kidneys and aldosterone
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Why is temperature important for the cell membrane?
Too cold – proteins slow down; membrane less fluid Too hot – proteins denature; increased membrane fluidity
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Why is pH regulation important for cell membranes?
Both extremes damage protein Inhibits cell function
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Why is the cell membrane selectively permeable?
Maintains the internal environment
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What are some features of the channel proteins in the cell membrane?
Narrow aqueous pore Selective: size and charge dependent Passive May be gated (voltage or ligand) Usually ions (e.g. Na+, K+) or water (aquaporins) going through
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What are some features of the carrier proteins in the cell membrane?
Specific binding site Carrier undergoes a conformational change Different types: Uniport – single substance Symport – two substances in the same direction Antiport – two substances in the opposite direction Active (pumps) or passive
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What are the 3 main forces driving things across the membrane?
Chemical Electrical Electrochemical
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How does the chemical driving force work?
Based on concentration differences across the membrane Force directly proportional to the concentration gradient
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How does the electrical driving force across the membrane work?
Membrane potential Based on the distribution of charges across the membrane Only charged substances e.g. Na+, K+ Force depends on size of membrane potential and charge of the ion
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How does the electrochemical driving force work?
Combines the chemical and electrical forces Net direction is equal to the sum of chemical and electrical forces Only charged substances e.g. Na+, K+
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What are the 2 types of passive transport?
Simple diffusion Facilitated diffusion (mediated by proteins)
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What happens in passive transport?
Does not require an input of energy Substance moves down its gradient (high to low) E.g. glucose via GLUT4
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How does active transport work?
Requires an input of energy Substance moves against its gradient (low to high) Primary and secondary
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What happens in primary active transport?
Directly uses a source of energy, commonly ATP E.g. sodium potassium atpase
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What does the sodium potassium pump do?
Pumps 3 Na+ out of the cell, 2 K+ into the cell
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What happens in secondary active transport?
Transport of a substance against its gradient coupled to the transport of an ion (usually Na+ or H+), which moves down its gradient Uses energy from the - generation of the ions - electrochemical gradient (usually by primary active transport) E.g. Na+/Glucose SLGT
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What is cAMP?
A secondary messenger
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What is a coenzyme?
cannot in themselves catalyze a reaction but can help enzymes to do so Bind with the enzyme protein molecules to form active enzymes
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What is a splice site mutation?
affects the accurate removal of an intron
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What is ATP?
a high-energy molecule composed of adenine (purine base), ribose, and three phosphate groups
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Steps of glycolysis
Glucose Glucose-6-phosphate Fructose-6-phosphate Fructose-1,6-bisphosphate DHP and Glyceraldehyde-3-phosphate 1,3-bisphosphoglycerate 3-phosphoglycerate 2-phosphoglycerate Phosphoenolpyruvate Pyruvate
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What is the rate-limiting step of glycolysis?
Fructose-6-phosphate to fructose-1,6,bisphosphate ATP to ADP Catalysed by phosphofructokinase 1 Irreversible
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What are the 3 irreversible steps of glycolysis?
Glucose to glucose-6-phosphate (hexokinase) Fructose-6-phosphate to fructose-1,6-bisphosphate (PFK1) Phosphoenolpyruvate to pyruvate (pyruvate kinase)
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What steps form ATP in glycolysis?
1,3-bisphosphoglycerate to 3-phosphoglycerate forms 2 ATP Phosphoenolpyruvate to pyruvate forms 2 ATP
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Which steps of glycolysis require ATP?
Glucose to glucose-6-phosphate Fructose-6-phosphate to fructose-1,6-bisphosphate
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Which step of glycolysis produces water?
2-phosphoglycerate to phosphoenolpyruvate
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Which step of glycolysis produces NADH?
G3P to 1,3-bisphosphoglycerate
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Where does glycolysis occur?
Cytoplasm of all cells
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What is the ATP exchange in glycolysis?
2 ATP used 4 ATP made
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What happens in glycolysis if there isn't enough oxygen?
Lactate dehydrogenase removes H from NADH to make pyruvate Also makes lactate and NAD+ NAD+ keeps glycolysis going
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What enzyme gets Acetyl CoA from pyruvate?
Pyruvate dehydrogenase
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What enzymes regulate glycolysis?
Kinases PFK1 main regulator
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What enzymes regulate the krebs cycle?
4 Dehydrogenases
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Where does Krebs take place?
Occurs in mitochondrial matrix Aerobic conditions
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What does Krebs do?
Generates 30-36 ATP Provides final common pathway for oxidation of carbohydrates, fat & protein via acetyl CoA Produces intermediates for other metabolic pathways
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Stages of Krebs cycle
Acetyly CoA combines with oxaloacetate Citrate Isocitrate alpha-ketoglutarate succinyl-CoA succinate fumarate malate back to oxaloacetate
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What regulates pyruvate dehydrogenase?
ATP and NADH, acetyl coa inhibit ADP and pyruvate activate
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What regulates citrate synthase?
ATP, NADH, Citrate, Succinyl CoA inhibit ADP stimulates
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What is the rate limiting step in Krebs?
Isocitrate to alpha-ketoglutarate Enzyme: isocitrate dehydrogenase NADH and CO2 out
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Which steps in Krebs produce NADH?
Isocitrate to alpha-ketoglutarate alpha-kg to succinyl-CoA malate to oxaloacetate
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Which step in Krebs produces FADH2?
Succinate to fumarate
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Which steps in Krebs produce CoA?
Acetyl and oxaloacetate to citrate Succinyl-CoA to succinate
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Which steps in Krebs send out CO2?
Isocitrate to alpha-ketoglutarate alpha-kg to succinyl-CoA
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What inhibits and stimulates isocitrate dehydrogenase?
ATP and NADH inhibit ADP stimulates
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Where does oxidative phsophorylation occur?
Occurs in the inner mitochondrial membranes aerobic conditions
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How does oxidative phosphorylation work?
NADH and FADH2 donate their electrons Electrons passed down chain Energy generated and used to pump H+ into intermembrane space Electrochemical gradient between intermembrane space and matrix Protons reenter matrix via ATP synthase Energy from this makes ATP from ADP