IMMS Flashcards

1
Q

What is the purpose of mitosis?

A

Makes 2 genetically identical daughter cells
Growth
Replaces dead cells

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2
Q

Describe prophase and metaphase

A
  • Prophase: chromatin condenses into chromosomes, centrosomes nucleate microtubles and move to opposite poles of nucleus
  • Pro metaphase: nuclear membrane breaks down, chromatids attach to microtubules
  • Metaphase: chromosomes line up at equator
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3
Q

Describe anaphase and telophase

A

After metaphase:
- Anaphase: sister chromatids separate to opposite poles

  • Telophase: nuclear membranes reform, chromosomes uncoil to chromatin, cytokinesis starts
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4
Q

Key points of meiosis

A
  • 4 haploid daughter cells
  • genetically different, for diversity
  • 2 cell divisions
  • only in gametes
  • crossing over in prophase 1
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5
Q

Describe spermatozoa production

A

-Primordial germ cells undergo lots of mitoses to produce spermatogonia
-Meiosis begins at puberty
-Equal cytoplasm division, 4 gametes
-Millions constantly produced
-Takes 60-65 days

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6
Q

Describe egg production

A

-Primordial germ cell undergoes 30 mitoses to form oogonia
-Oogonia enter prophase of meiosis I by 8th month of intrauterine life, suspended
-Cells enter ovulation 10-50 years later
-Cytoplasm divides unequally – 1 egg and 3 polar bodies (that apoptose)
-Meiosis I is completed at ovulation
-Meiosis II only completed if fertilisation occurs

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7
Q

How does DNA coil into chromosomes?

A

-DNA winds around histones forming nucleosomes
-Nucleosomes coil into chromatin
-Chromatin coils into supercoils and chromosomes

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8
Q

What is euchromatin?

A

Actively transcribing cellular DNA
light staining

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9
Q

What is heterochromatin?

A

Transcripitionally inactive cellular DNA
Dense staining often adjacent to nuclear membrane
Highly condensed

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10
Q

What are the main parts of a chromosome?

A

P- short top arm
Q- long arm
Centromere- controls movement in division
Telomere- at tip, seals chromosome

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11
Q

Describe G-banding in chromosomes

A

Treated with trypsin
Stained with Giesma DNA-binding dye
Gives light and dark bands

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12
Q

What is the clinical relevance of cell division?

A
  • Detecting chromosomal abnormalities
  • Categorising tumours as B/M
    -Grading M tumours
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13
Q

What is nondisjunction?

A

Failure of chromosome pairs to separate in meiosis 1 or
Failure of sister chromatids to separate in meiosis 2

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14
Q

What is gonadal mosaicism?

A

Occurs when precursor germ line cells are a mixture of two or more genetically different cell lines
One cell line is healthy, one is mutated
Increases with parent’s age

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15
Q

Examples of gonadal mosaicism

A

More common in autosomal dominant or x linked
Osteogenesis imperfecta
Duchenne muscular dystrophy

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16
Q

Clinical relevance of mitotic spindle (drugs)

A

Taxol
Vinca alkaloids
Spindle poles- ispinesib

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17
Q

Clinical relevance of anaphase

A

Colchicine like drugs

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18
Q

Anagram for recognising rare disease

A

G - group of congenital abnormalites
E- extreme presentation of common conditions
N- neurodevelopmental disease/ early onset NG
E- extreme pathology
S- surprising lab results

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19
Q

What are constitutional chromosomal abnormalities?

A

Present from birth
Occurs at gametogenesis
Affects all cells
Heritable

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20
Q

What are acquired chromosomal abnormalities?

A

Changes occur during lifetime
Restricted to malignant tissue
Not heritable

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21
Q

What are fusion genes?

A

Breakpoints occur within two genes
Hybrid gene created
Chimaeric protein

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22
Q

What is gene deregulation?

A

Juxtaposition of gene to regulating gene
Altered regulation result in increased transcription and neoplastic growth

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23
Q

Define genotype

A

Genetic constitution of an individual

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24
Q

Define phenotype

A

appearance of individual (physical, biochemical, physiological) which results from interaction of genotype and environment

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25
How to karyotype cell/tissue types
-Obtain sample and add to culture medium + PHA -Incubate at 37 degrees for 48-72hrs -Add colcemid + hyptonic solution -Fix, mount on slide and stain cells
26
Genetics of Downs
47, XX/XY, +21 Trisomy 21 1/700 chance
27
Genetics of Edwards syndrome
47, XX/XY, +18 Trisomy 18 1/3000 chance
28
Genetics of Patau
47, XX/XY, +13 Trisomy +13 1/5000
29
Examples of sex chromosome abnormalities
47, XXY, Klinefelter, 1/1000 male births 47, XXX, Triple X, 1/1000 female births 45, X, Turner, 1/2500
30
What is reciprocal translocation?
-Involves the breakage of at least 2 chromosomes, with fragments exchanging -Chromosome number usually remains at 46 E.g. 46, XY, T(2:18) or Robertsonian
31
What is FISH?
-Fluorescent In-Situ Hybridization -DNA probe labelled with fluorochrom -Hybridized and area visible with fluorescent microscope -Used for diagnostic purposes
32
What is a deletion?
-loss of 1+ nucleotides -large deletions usually incompatible with survival -e.g. cri du chat
33
Role of cytogenetics
-confirmation of malignancy -classification of disease type -prognosis -monitoring
34
About microarrays
-simultaneous analysis of several million targets -short, fluorescent labelled oligonucleotides attach to microscope slides -hybridization of target DNA detected
35
What is array CGH?
-Comparative genomic hybridization -hybridization of patient and reference DNA
36
How do multifactorial risks vary in families?
- Dramatically higher in relatives - Degree of genetic relationship - Number of relatives affected - Severity
37
Characteristics of multifactorial inheritance
- incidence greatest amongst relatives of patients - greatest risk for first degree relatives, decreases with extended family - more affected relatives = higher risk
38
About macromolecules
- formed by simple molecules (amino acids, lipids, sugars) - have osmotic, optical, structural and enzymatic functions - heterogenous structures e.g. haemoglobin, DNA, glycogen
39
Types of carbohydrates
Monosaccharides Disaccharides Polysaccharides Oligosaccharides
40
About monosaccharides
- Chains of carbons, hydroxyl group and one carbonyl - aldose has a C1 aldehyde - ketose has a ketone - generally ring structures e.g. glucose, glyceraldehyde, ribose produced by digestion
41
Which glycosidic bond is found in carbs and nucleotides?
O-glycosidic in carbs N-glycosidic in nucleotides
42
About oligosaccharides
- Between 3-12 monosaccharides - Products of digestion of poly/ parts of complexes - n- linked sugars
43
About polysaccharides
- Thousands of MS with glyc bonds - Starch, glycogen
44
What are proteoglycans?
- long, unbranched PS radiating from core protein
45
About fatty acids
- Straight C chains with methyl and carboxyl groups at ends - Saturated or unsaturated
46
What are steroids?
- Cholesterol is precursor to all human steroids - Have a 4 ring structure called steroid nucleus
47
Nucleoside structure
A nitrogenous base joined to a sugar through a n-glycosidic bond
48
Nucleotide structure
Nucleoside + phosphate
49
Which bases are purines and pyramidines?
Purine: A & G, 2 rings Pyramidine: T, C, U, 1 ring
50
What are amino acids?
- Contain an amine group and a carboxylic acid group - Side chain (R) often determines polarity - Charge determined by all 3 components, can change at different pH
51
Properties of peptide bonds
- very stable - cleaved by proteolytic enzymes - partial double bond - flexibility around C atoms not in bond allows multiple conformations
52
What forces can hold proteins together?
- London (when close fit) - H bonds (between dipoles) - Hydrophobic (pack in protein interior) - Ionic (between charged groups) - Disulphide (covalent between cysteine R)
53
Primary structure of a protein
- linear sequence of aa - determines 3D conformation
54
Secondary structure of a protein
- alpha helices (H bonds between aa) - beta sheets (pleated or not, between linear polypeptide chains, parallel if strands run in same direction)
55
Tertiary structure of a protein
- overall 3D conformation of protein - contains range of forces - can change with pH
56
Quaternary structure of a protein
- association of individual polypeptide chain subunits - same non-covalent interactions as tertiary
57
About enzymes
- biological catalysts - binds the substrates, brings them at right orientation for reaction, releases products and remains unchanged
58
About myoglobin
- globular protein composed of a single polypeptide chain with 1 O2 binding site - present in heart and skeletal muscle - can bind the O2 released from haemoglobin
59
About haemoglobin
- tetramer composed of two different types of subunits, 2 alpha and 2 beta polypeptide chains - heme consists of planar porphyrin ring, Fe in centre binds to 4 N, Fe site of O2 binding
60
What is the immunoglobulin (antibody) structure?
- 2 identical small (light) + 2 identical large (heavy) polypeptide - Chains joined by disulphide bonds - Both light and heavy regions contain variable (V) and constant (C) regions - V regions interact to produce single antigen binding site at each branch - summary: supporting scaffold to display complementarity determining regions
61
How do the CDR of immunoglobulins work for binding?
- Wide range of reversible bonding between antigen and antibody - very close proximity of antigen surface and cdr - CDR has AA sequence that complements antigen
62
What is the portion of the antigen bound known as?
Epitope
63
Which bases pair and why is DNA base pairing good?
- Adenine and thymine, 2 H bonds - Cytosine and guanine, 3 H bonds - Purines flip over to be in correct orientation - Pairing allows one strand of DNA to serve as a template for other strand and also RNA
64
What does antiparallel mean?
- 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
65
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
66
Describe the process of DNA replication (S phase)
1. DNA helicase disrupts binding to open into replication fork 2. Leading strand runs 3' to 5', lagging is 5' to 3' 3. RNA primer bonds to leading at 3' end 4. Leading strand replicated by polymerases, continuous 5. Lagging strand binds with multiple primers, polymerase adds DNA (okazaki fragments), discontinuous 6. When both strands formed, exonuclease removes primers and replace with bases 7. DNA Ligase joins lagging strand up 8. Telomerase catalyses synthesis of new telomeres at ends
67
About DNA polymerase in DNA replication
- Reads 3' to 5', prints 5' to 3' - Deoxyribonuceloside triphosphates serve as substrates for addition of nucleotides
68
What is the function of DNA?
- Template and regulator from transcription and protein synthesis - Structural basis of heredity and genetic disease
69
Which enzymes/proteins work to open the strands of DNA?
- Helicase opens it - Single stranded binding proteins keep it open - Topoisomerase unwinds supercoil
70
List some forms of DNA damage
- Ionising radiation: damage bases, break phosphate backbone - UV: Damage bases, e.g. thymine dimers - Spontaneous insertion of wrong bases in rep
71
What is the p53 protein and what does it do?
- 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
72
Examples of drugs used in cancer to interfere with DNA replication
- Inhibitors of nucleotide synthesis: methotrexate - DNA polymerase inhibitors: cytosine arabinoside - DNA template damaging agents: cyclophosphamide - Inhibitors of DNA topoisomerase: doxorubicin
73
What is the structure of mRNA?
- long linear transcript - 5' CAP and Poly(A) tail
74
What is the structure of a prokaryotic ribosome?
- 70S split into 50S and 30S subunits - 50S contains 5S and 23S rRNAs - 30S contains 16S rRNA complexed with proteins
75
What is the structure of 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
76
What is the structure and role of tRNA?
- Carry AA to ribosomes to ensure incorporated into appropriate positions - Many AAs have more than one tRNA, tRNAs only have one AA for their anticodon - Very small, around 80 nucleotides
77
Describe process of transcription + mRNA splicing
1. RNA polymerase binds to transcription factor complex in promoter region 2. Helix unwinds, synthesis of RNA transcript is initiated 3. Elongation of RNA transcript, DNA template copied, strands rejoin as polymerase passes 4. Reaches stop codon, RNA polymerase detaches, single strand of pre-mRNA - end of transcription 5. mRNA splicing occurs to remove introns 6. mRNA leaves via nuclear pore into cytoplasm
78
Describe the process of translation
1. Complex forms between met-tRNA, ribosome and mRNA 2. Small ribosome subunit binds to 5' end of mRNA, scans until reaches start codon 3. tRNA binds to ribosome and amino acid added, peptide bonds 4. Polypeptide chains become larger and start to fold, end of translation
79
How is gene expression initiated
1. Transcription factors at promoter region. Transcription complex forms at TATA box 2. Helix opens, DNA strands separate 3. RNA polymerase II starts building mRNA
80
Roles of the RNA polymerases
I - produces most of the rRNAs II- produces mRNA III- produces small RNAs Same mechanism, recognize different promoters
81
What is chromosome 22q11 deletion syndrome?
DiGeorge syndrome/ Velocardiofacial syndrome 1 in 4-6,000 Congenital heart diseases -74% Palatal abnormalities- 69% Learning difficulties- 70-90% Immunodeficiency- 77% 90% de novo, 10% inherited
82
What is Mendelian inheritance?
Autosomal and sex-linked Dominant or recessive
83
What is non-Mendelian inheritance?
Imprinting Mitochondrial inheritance Multifactorial Mosaicism
84
Describe cystic fibrosis (genetics)
1 in 2,500 Autosomal recessive CFTR gene on7q31.2 Over 1,000 mutations- mutational heterogeneity
85
Examples of autosomal recessive diseases
Haemochromatosis CF Sickle cell Deafness
86
Describe X-linked inheritance
Genes carried on the X chromosome Usually only males affected No male to male transmission An affected male cannot have an affected son, but can have carrier daughters
87
What are mitochondrial genetic diseases?
Group of disorders caused by dysfunctional mitochondria Caused by mutations in mitochondrial DNA/ nuclear genes whose products are imported into the mitochondria
88
What does mRNA splicing allow?
If alternative splicing, different proteins can be made from the same gene Exon shuffling allows new proteins to be made, e.g. immune system
89
Types of variants in genes
- Deletions: whole gene or some exons - Duplications of gene or parts of gene - Splice site variants, frameshift mutations, affects accurate removal of an intron - Missense: base pair sub leads to different AA - Nonsense: sub leads to generation of stop codon and premature end of translation
90
Diseases caused by expansions of trinucleotide repeats
Huntington's - CAG Myotonic dystrophy - CTG, also example of anticipation Fragile X - CGG
91
What are loss of function variants?
- Only one allele functioning - Most recessive - Haploinsufficiency
92
What are gain of function variants?
- Increased gene dosage - Increased protein activity
93
What are dominant-negative variants?
Where the protein from the variant allele interferes with the protein from the normal allele
94
When would you carry out a diagnostic test?
Patient has signs and symptoms suggesting condition A molecular genetic test will confirm a diagnosis Issues informed consent
95
When would you carry out predictive testing?
Testing at risk family members for a previously identified familial variant
96
When would you carry out carrier testing?
Couple testing, individua not usually helpful Reproductive decision making Recessive or X-linked conditions
97
When would you carry out pre-natal testing?
Performed in pregnancy when there is an increased risk of foetus being affected Counselling issues CVS or amniocentesis
98
What is PGD?
Pre-Implantation genetic diagnosis 8-cell embryo has one cell removed under gentle suction Single cell free for analysis
99
What is Sanger screening?
Uses PCR to amplify regions of interest followed by sequencing of products Useful for single gene testing High cost per gene and time consuming Simple analysis but very accurate
100
What is next generation sequencing?
Massively parallel sequencing Can sequence whole genome in a day Multi gene panels Low cost per gene and fast Moderately accurate Huge amounts of data
101
What does metabolism refer to?
The sum of chemical reactions that take place within each cell in the organism
102
What are the 4 main metabolic pathways?
Biosynthetic- anabolic Fuel storage- anabolic Oxidative processes- catabolic Waste disposal- either
103
What are the uses of dietary components?
Body components Fuel stores Energy Waste products
104
What is the structure of ATP?
Adenine 5'-triphosphate Adenine Ribose 3 Phosphate groups
105
Purpose of ATP to ADP
Reaction is energetically favourable, negative Gibbs Hydrolysis Energy utilization E.g. biosynthesis, active ion transport, muscle contraction
106
Purpose of ADP to ATP
Energy production via oxidation of carbs, lipids, proteins
107
Brief description of glycolysis
Anaerobic breakdown of glucose to pyruvate Small amount of ATP from substrate level phosphorylation Occurs in cytosol
108
Brief description of Krebs cycle
Oxidation of acetyl CoA Coenzymes NADHand FADH2
109
Brief description of oxidative phosphorylation
Transduction of energy derived from fuel oxidation to high energy phosphate Generates large amounts of ATP
110
What is the equation for glycolysis?
Glucose + 2NAD + 2 Pi + 2ADP ----> 2 Pyruvate + 2NADH + 4H + 2ATP + 2H2O
111
Brief summary of the prep phase in glycolysis
Glucose. 2 ATP in, forms Fructose-1,6-bisphosphate
112
Brief summary of the ATP generating phase of glycolysis
2 triose phosphates, 2NADH 2ATP 2ATP generated, 2 pyruvate
113
Stages of glycolysis prep phase
-Glucose to (ATP to ADP, hexokinase) -Glucose 6-phosphate to (phosphoglucose isomerase) -Fructose 6-phosphate to (ATP to ADP, phosphofructokinase-1) -Fructose-1,6-bisphosphate to (aldolase) -Dihydroxyacetone phosphate or (triose phosphate isomerase) -glyceraldehyde 3-phosphate
114
Stages of glycolysis ATP generating phase
-Glyceraldehyde 3-phosphate to (triose phosphate dehydrogenase, 2 NADH + 2 H) -1,3-bis-phosphoglycerate to (ADP to ATP, phosphoglycerate kinase) -3-Phosphoglycerate to (phosphoglyceromutase) -2-Phosphoglycerate to (enolase, H2O out) -Phosphoenol pyruvate to (ADP to ATP, pyruvate kinase) -Pyruvate
115
What is regulated in glycolysis?
Hexokinase Phosphofructokinase-1 Pyruvate kinase Dehydrogenase
116
What is the rate limiting enzyme in glycolysis?
Phosphofructokinase-1 Controls the rate of glucose 6-phosphate into glycolysis Allosteric enzyme with 6 binding sites
117
What are allosteric activators and inhibitors?
Compounds that bind at sites other than the active site that regulate the enzyme through conformational changes that affect the catalytic site
118
What are the two main hormonal regulators of glycolysis and how does it work?
Insulin: activates key glycolytic enzymes Glucagon: inactiveates key glycolytic enzymes Indirect Glycolytic enzymes are sensitive to cell's energy levels
119
How is phosphofructokinase-1 regulated in glycolysis?
ATP: inhibits PFK1 AMP (when ATP is used up): activates PFK1 to make more ATP in glycolysis Citrate from Krebs: inhibits PFK1 as more energy isn't needed Fructose 2,6-bisphosphate: activates PFK1, also mediates effects of insulin and glucagon
120
Formula for glycolysis in anaerobic conditions
glucose + 2ADP + 2Pi → 2lactate + 2ATP + 2H2O + 2H+
121
What happens to pyruvate in anaerobic conditions?
Lactate dehydrogenase reaction Pyruvate reduced to lactate in cytosol, NADH required Lactate and H+ transported out of cell into interstitial fluid and diffuse into blood If exceeds buffering range of blood, lactate acidosis Reversible
122
What happens to pyruvate in aerobic conditions?
Irreversible In mitochondrial matrix, catalysed by pyruvate dehydrogenase pyruvate + CoA + NAD+ ------> acetyl-CoA + CO2 + NADH + H+ Inhibited by high concs of products Inactivated by phosphorylation, activated by phosphate removal
123
Brief description of Krebs/TCA
In mitochondrial matrix, aerobic aka tricarboxylic acid cycle Generates lots of ATP and intermediates for other metabolic pathways
124
Overall equation for Krebs
acetyl-CoA + 3NAD+ + FAD + GDP + Pi + 2H2O ------> 2CO2 + 3NADH + FADH2 + GTP + 3H+ + CoA
125
Describe the stages of the TCA cycle to succinyl CoA
-Acetyl CoA to (citrate synthase) -Citrate to (aconitase) -Isocitrate to (NAD+ to NADH + H+, CO2 out, isocitrate dehydrogenase) -alpha-ketoglutarate to (NAD to NADH + H+, CO2 out, alpha-ketoglutarate dehydrogenase) -Succinyl CoA
126
Describe the stages of the TCA cycle from succinyl CoA to oxaloacetate
-Succinyl CoA to (GDP +Pi to GTP, succinate thiokinase) -Succinate to (FAD TO FAD2H, succinate dehydrogenase) -Fumarate to (fumarase) -Malate to (NAD to NADH + H+, Malate dehydrogenase) -Oxaloacetate to -Acetyl CoA
127
TCA A... C... I... K... S... S... F... M... O...
Aceytl CoA Citrate Isocitrate alpha-ketoglutarate Succinyl CoA Succinate Fumarate Malate Oxaloacetate
128
Glycolysis G... G... F... F... D.../G... B... P... P... P... P...
Glucose Glucose 6-Phosphate Fructose 6-Phosphate Fructose 1,6-bisphosphate Dihydroxyacetone phosphate/ glyceraldehyde 3-phosphate 1,3-bisphosphoglycerate 3-phosphoglycerate 2-phosphoglycerate Phosphoenol pyruvate Pyruvate
129
Describe the regulation of enzymes in Krebs
Isocitrate dehydrogenase: inhibited by ATP, NADH, activated by ADP Citrate synthase: inhibited by ATP, NADH, Citrate, activated by ADP alpha-ketoglutarate dehydrogenase: inhibited by ATP, NADH, GTP, Succinyl CoA, activated by Ca2+
130
How is pyruvate dehydrogenase regulated?
Inhibited by: ATP, NADH, Acetyl CoA Activated by: ADP, pyruvate
131
Brief description of oxidative phosphorylation
In the inner mitochondrial matrix aerobic NADH and FADH2 through electron transport chain Produces O2 and ATP Releases majority of energy during cellular respiration
132
Describe the process of oxidative phosphorylatin
1. NADH or FADH2 donate electrons 2. electrons move along electron transport chain: accepted via reduction, move on (oxidation). NADH electrons move down complex I, complex III and complex IV 3. At each of the complexes, e- transfer is accompanied by proton pumping across membrane into inter membrane space 4. Drop in energy as electrons move down conc gradient 5. matrix more alkaline as H+ moved out, and more -ve so protons draw back in, via ATP synthase 6. 12 protons synthesize 3 ATP
133
What is adipose tissue specialised for?
85% fat Storage of energy-rich molecules
134
What is liver tissue specialised for?
metabolically active e.g. gluconeogenesis, removal of toxins
135
What is the cori cycle?
Metabolic route to get rid of lactate and keep producing energy anaerobically Lactate returns to liver and is reconverted to glucose via gluconeogenesis
136
What is gluconeogenesis?
Formation of new glucose by the liver Converts new non-carbohydrates to glucose, e.g. lactate, glycerol, AAs
137
Functions of insulin
-Promotes fuel storage after a meal -Promotes growth -Stimulates glucose storage as glycogen -Stimulates fatty acid synthesis and storage after a high-carb meal -Stimulates amino acid uptake and protein synthesis
138
Functions of glucagon
-Mobilisizes fuels -Activates gluconeogenesis and glycogenolysis during fasting -Activates fatty acid release from adipose tissue
139
Storage of dietary fuels: fat, carbohydrate, protein
Fat- adipose tissue (only 15% water) Carbohydrate- as glycogen in liver and muscles Protein- muscle (80% water)
140
What happens to excess energy intake?
- store as triglycerides in adipose (15kg) - store as glycogen (200g in liver, 150g in muscle), 80g in the liver after overnight fast - store as protein in muscle (6kg)
141
How much energy per gram of carb, protein, lipid, alcohol
Carbohydrates: 4kcal Protein: 4kcal Alcohol: 7kcal Lipid: 9kcal
142
What is BMR?
A measure of energy needed to maintain non-exercise bodily functions
143
List examples of non-exercise bodily functions for BMR
-Respiration -contraction of the heart muscle -biosynthetic processes -repairing and regenerating tissues -ion gradients across cell membranes
144
What are the conditions for measuring BMR?
- 12hour fast - lying still at rest - 27-29 degrees environment - no tea, coffee, nicotine, alcohol in previous 12 hours - no heavy physical activity previous day - establish steady state for 30 minutes
145
Factors decreasing BMR
Age Males lower than females Dieting/ starvation Hypothyroidism Decreased muscle mass
146
Factors increasing BMR
Higher BMI Hyperthyroidism Low ambient temp Fever/infection/chronic disease
147
What happens if starvation occurs for 2-4 days?
insulin drops, cortisol rises gluconeogenesis
148
What happens if starvation occurs for more than 4 days?
Liver makes ketones from fatty acids Brain adapts to using ketones BMR decreases
149
What is re-feeding syndrome?
Potentially fatal condition Severe electrolyte and fluid shifts as a result of a rapid reintroduction of nutrition after a period of inadequate nutritional intake
150
Function of vitamin C (ascorbic acid)
- collagen synthesis - improve iron absorption - antioxidant
151
Function of vitamin B12
- protein synthesis - DNA synthesis - regenerate folate - fatty acid synthesis - energy production
152
Function of vitamin B1
- B1 (thiamine): break down and release energy from food, keep NS healthy
153
Function of folate
-Helps to produce and maintain DNA and cells -Helps make enough RBCs -Enough folic acid reduces risk of baby having birth defects
154
Function of vitamin A
- Helps vision in dim light - Helps natural defence against infection - Promotes normal growth and development - Keeps skin healthy
155
Function of vitamin D
- increases amount of calcium and phosphorus your body absorbs from food - deposits calcium and phosphorus in bones and teeth to keep them strong and healthy
156
Function of vitamin E
- Helps maintain a healthy immune system and other body processes - Acts as an antioxidant and protects cells from damage
157
Function of vitamin K
- Makes proteins that cause our blood to clot - Involved in making body proteins for blood, bones and kidneys
158
Features of a prudent diet
-5 a day -5% max energy from free sugars -0.8g/kg/day protein -no more than 20g (women) 30g (men) saturated fat a day -no more than 2.4g sodium (6g salt) a day -avoid excess dietary supplementation -adequate calcium - no more than 14 units alcohol a week
159
Function of vitamin B2
(riboflavin): energy production from food
160
Function of vitamin B3
B3 (niacin): helps body to use fat, carbs and protein for energy, helps enzymes work
161
Function of vitamin B6
B6 (pyridoxin): helps make and use protein and glycogen, helps form haemoglobin
162
Function of vitamin B7
B7 (biotin): in small amounts, allows body to use protein fat and carbs from food, make fatty acid
163
What are the stages of lipid absorption and transport?
1. Bile salts emulsify dietary fats in the small intestine, forming mixed micelles 2. Intestinal lipases degrade triacylglycerols 3. Fatty acids and other breakdown products are absorbed by intestinal mucosa, bile salts left and resorbed 4. FAs converted into triacylglycerols, then incorporated with cholesterol and apoproteins to form chylomicrons 5. Move through lymphatic and bloodstream to tissues 6. Lipoprotein lipase releases FAs and glycerol 7. FAs enter cells
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Describe process of fatty acid activation
Pre-oxidation Acyl-CoA synthetase + energy from ATP FA ----> fatty acyl AMP intermediate and pyrophosphate (PPi) PPi cleaved to drive reaction forming fatty acyl CoA If acyl-CoA has less than 12C, it diffuses through mitochondrial membrane 12-14C are taken through mitochondria via carnitine shuttle
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Describe process of FA β-oxidation
Fatty acyl CoA ------> acetyl CoA for Krebs 1. Acyl CoA to (FAD to FADH2, acyl CoA dehyrdogenase) 2. trans fatty enoyl CoA to (H2O in, enoyl CoA hydratase) 3. L-β-Hydroxy acyl CoA to ( NAD+ to NADH + H+, β-hydroxy acyl CoA dehydrogenase) 4. β-keto acyl CoA to (CoASH in, β-keto thiolase) 5. Acetyl CoA
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Basic stages of reaction types in FA β-oxidation
1. Oxidation 2. Hydration 3. Oxidation 4. Thiolysis
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Where does acetyl-CoA go after FA oxidation?
Most goes to TCA cycle Some converted into ketones An excess leads to ketogenesis
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What is ketogenesis?
Metabolic pathway that produces ketone bodies
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What makes up the lipid bilayer?
Intergral proteins Peripheral proteins Glycolipids Glycoproteins Cholesterol to aid fluidity Phosolipids
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Describe channel proteins
Integral, span both layers Selective (size, charge etc...) Passive May be gated
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What is role of carrier proteins?
Transport large protein molecules
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What are the different types of carrier protein and their roles?
Uniport – single substance Symport – two substances in the same direction Antiport – two substances in the opposite direction
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Features of a carrier protein
Specific binding site Carrier undergoes a conformational change Active pumps or passive
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How does a chemical driving force across a membrane work?
Based on concentration differences across the membrane All substances have a concentration gradient Force directly proportional to the concentration gradient
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How does an electrical driving force work across a membrane?
Also known as 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 an electrochemical driving force work across a membrane?
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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How does passive transport work?
Does not require an input of energy Substance moves down its gradient (high to low)
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What are the 2 types of passive transport?
Simple diffusion e.g. gases Facilitated diffusion - mediated by proteins (channel or carrier)
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How is glucose taken up across a membrane?
GLUT4 carrier protein: Expressed in skeletal muscle and adipose tissue Glucose uptake by facilitated diffusion Expression upregulated by insulin
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What is GLUT1 and its deficiency?
GLUT1 present in many cells, including the brain, where it transports glucose across the blood-brain barrier via facilitative diffusion GLUT1 Deficiency Syndrome: - Very rare disorder - Mutations in gene that encodes GLUT1 - Less functional GLUT1 - reduces the amount of glucose available to brain cells - Symptoms include seizures, microcephaly, developmental delay
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How does active transport work?
Requires an input of energy Substance moves against its gradient (low to high)
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What is primary active transport?
Directly uses a source of energy, commonly ATP Common example is Na+/K+-ATPase: - Pumps 3 Na+ out of the cell, 2 K+ into the cell - Utilises the hydrolysis of ATP to ADP + Pi
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What is 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) Example is the Na+/glucose cotransporter proteins (SGLT)
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What do proteins in SGLT1 do?
Present in intestinal lumen and renal tubules Transports glucose from low to high concentration Na+/K+-ATPase generates a sodium gradient to enable co-transport of sodium and glucose
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What is glucose-galactose malabsorption?
Very rare disorder Mutations in SGLT1 Less functional SGLT1 -inability to transport glucose and galactose, resulting in their malabsorption Symptoms include severe, chronic diarrhoea, dehydration, failure to thrive
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What is cell signalling?
- Communication between cells takes place via signalling molecules e.g. hormones, neurotransmitters and growth factors - Signalling molecules bind to receptors: - Intracellular – e.g. steroid hormones - Cell-surface – e.g. peptide hormones - Second messengers (cAMP, IP3, DAG, Ca2+) - amplification - Affect gene expression in the nucleus either directly or through signalling cascades
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What is endocytosis?
Allow larger molecules that cannot diffuse through the lipid bilayer to cross the membrane Foreign material is engulfed within the cell membrane, which then forms a vesicle containing the ingested material
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What are the subtypes of endocytosis?
Phagocytosis- immune purposes e.g. bacteria Pincytosis – non-specific uptake of fluid surrounding the cell, allowing it to take in nutrients such as ions, enzymes and hormones Receptor-mediated endocytosis – uptake of specific target substances, such as iron, via their receptor
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What is exocytosis and how does it work?
Form of active transport through which large molecules are moved from the interior to the exterior of the cell Vesicles are packaged within the cell and transported to the cell membrane, where their phospholipid bilayers fuse Contents released outside the cell