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MRCOG Part 1 > Biochemistry > Flashcards

Biochemistry Flashcards

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1
Q

Eukaryotic cells

A

Protista, fungi, plants, animals
10-100μm
Nucleus - spherical, largest organelle, surrounded by double membrane nuclear envelope, contains nucleolus (that synthesizes ribosomal RNA) and genetic material
Chromosome is linear molecule with histone proteins
Plasma membrane - phospholipid bilayer, semi-permeable with receptor proteins
+- cell wall
Cytoplasm - for cellular shape and integrity, has cytoskeletons (for cytokinesis and endocytosis) and membrane-bound organelles (endoplasmic reticulum rough w ribosomes or smooth, golgi apparatus, mitochondria (powerhouse with maternal genetic material, self-replicating), lysosomes and peroxisomes (digestive enzymes, acidic)
Cell division mitosis or meiosis

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2
Q

Prokaryotic cells

A

Mainly bacteria
1-10μm
No membrane bound organelles
No nucleus, nuclear material lies in cytoplasm
Chromosome usually circular
Can carry plasmids
Most have cell wall
No mitochondria
Cell division by binary fission

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3
Q

Signal transduction

A

Where external stimulus to cell is converted to specific cellular response eg activation of genes, metabolic alterations, proliferation of cell
Can be ms (ion influx) to days (gene expression)
Then intracellular signal transduction via second messengers

Signalling molecules - hormones, growth factors, cytokines, chemokines, neurotransmitters, extracellular matrix components
Act on cellular receptors - cell surface (endocrine via blood, paracrine to local cells, autocrine to own cell producing hormone) or intracellular

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4
Q

Cell surface receptors

A

Ion-channel-linked receptors - voltage-gated (Na/Ca/K) or ligand gated (nicotinic acetylcholine, GABA, 5-HT, glycine)

Enzyme-linked receptors - to activate tyrosine protein kinase, receptors for growth factors (tyrosine kinase, tyrosine phosphatase, guanylyl cylase, histidine kinase, serine)

G protein-coupled receptors - to activate G proteins (guanine nucleotide-binding proteins), have 3 subunits α β γ, only in eukaryotes (rhodopsin-like, secretin, metabotropic glutamate, cAMP)

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5
Q

Adrenergic receptors

A

In G protein-coupled receptor family
Promote glycogenolysis and gluconeogenesis from adipose tissue and liver

α antagonists
β antagonists

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6
Q

α antagonists

A

For BPH/HTN

α1 eg tamsulosin, prazosin, doxazosin
- activation of phospholipase C, so increasing IP3 and diacylglycerol, to increase intracellular Ca
- drugs -> smooth muscle relaxation (ureter, urethral sphincter, uterus) and smooth muscle contraction of GI tract, vasodilation of arteries and veins, inhibit glycogenolysis and gluconeogenesis

α2 mainly in research
- inactivation of adenylate cyclase leading to decreased intracellular cAMP

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7
Q

β antagonists

A

β1
- activation of adenylate cyclase, increased intracellular cAMP, activate protein kinase A
- chronotropic and inotrophic effect on heart, renin release, lipolysis in adipose tissue

β2
- smooth muscle relaxation (bronchi, uterus, detrusor, GItract), contracts anal sphincter, vasodilatory

β3
- lipolysis in adipose

eg NON-SELECTIVE propanolol, CARDIOSELECTIVE β1 atenolol, metoprolol, bisoprolol, MIXED α1β1 labetalol carvedilol

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8
Q

α and β agonists

A

α1 agonist - phenylephrine, noradrenaline

α2 agonist - clonidine

β1 agonist - noradrenaline, isoprenaline, dobutamine

β2 agonist - salbutamol, isoprenaline, terbutaline

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9
Q

Acetylcholine

A

Neurotransmitter in brain and ANS
Only neurotransmitter at neuromuscular junction
eg nicotinic and muscarinic receptors
Both PREganglionic sympathetic and parasympathetic fibres are cholinergic
All POSTganglionic parasymp fibres are cholinergic
All POSTganglionic symp fibres are adrenergic

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10
Q

Nicotinic receptors

A

Ionotrophic receptors
Form ligand-gated ion channels in plasma membrane on postsynaptic side of NMJ
No secondary messengers
Muscle type or neuronal type
Stimulation -> excitatory postsynaptic potential in neurones

Agonists - acetylcholine, choline, nicotine, suxamethonium
Antagonists - pancuronium, tubocurarine, atracurium

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11
Q

Muscarinic receptors

A

G protein-coupled receptors
5 subtypes - M1 exocrine and CNS, M2 heart, M3 blood vessels lungs and salivary glands, M4 CNS

M2 and M4 decrease intracellular cAMP
M1, M3, M5 upregulate phospholipase C and so inositol triphosphate and intracellular Ca
Work to increase exo and endocrine secretions, decrease HR, reduce cardiac contractility, smooth muscle contraction (bronchoconstriction), vasodilation, eye accommodation and pupillary constriction

Agonists - acetylcholine, muscarine, pilocarpine
Antagonists - atropine, scopolamine, ipratropium, tolterodine, oxybutinin

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12
Q

Acetylcholine receptor blocking agents

A

Non-depolarizing - work by blocking the binding of ACh to receptor - tubocurarine, pancuronium

Depolarizing - by depolarizing plasma membrane of skeletal muscle fibre - suxamethonium

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13
Q

Intracellular receptors

A

eg cytoplasmic and nuclear receptors

Exclusively intracellular receptors are steroid hormone, thyroid hormone, retinoic acid, vitD3 receptors

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14
Q

Intracellular second messengers

A

Ca ions
Lipophilic messengers - diacylglycerol, IP3
cAMP - synthesized from ATP by adenylate cyclase, activates protein kinase A
cGMP - synthesized from GTP by guanylate cyclase, activate protein kinase G, relaxes smooth muscle, degraded by phosphodiesterases
NO

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15
Q

NO

A

= endothelium-derived relaxing factor
- vasodilatation, modulation of hair cycle, penile erection

Biosynthesized from L-arginine -> NO + L-citrulline, catalysed by nitric oxide synthase NOS
3 types of NOS - endothelial (calcium-calmodulin dependent, 10s half life, acts on vascular smooth muscles, expressed by syncytiotrophoblasts), inflammatory (calmodulin INdependent, secreted by bacterial cell wall and neutrophils after activation by TNF or interferonγ), brain

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16
Q

Mechanism of action NO

A

Stimulate cGMP
Activates protein kinase G
Phosphorylates myosin light chain phosphatase
Inactivates myosin light chain kinase
Dephosphorylates myosin light chain
Smooth muscle relaxation

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17
Q

Carbohydrates

A

Made of carbon, hydrogen, oxygen only
Can be converted into fat, but fat cannot be converted into glucose
ATP stores energy, can be hydrolysed to release

Monosaccharides - fructose, glucose, galactose
Disaccharides - maltose, sucrose, lactose
Oligosaccharides - ABO blood groups
Polysaccharides - amyolse, glycogen

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18
Q

Glucose

A

C6H12O6
The ONLY subtance that can undergo anaerobic metabolism
2g/kg/day requirement, brain needs at least 25g/day in starvation or 100g/day normally
Low Km value (= high affinity of transporter protein)

Maltose = 2 units of glucose
Lactose = glucose + galactose (by lactase enzyme)
Sucrose = glucose + fructose (by sucrase enzyme)

Lactate is converted to glucose via Cori cycle

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19
Q

Glucose sources

A

Glycogen - stored in muscle (if G6PD can’t release into circulation) and liver, stores last 24hrs
Muscle protein conversion
Breakdown of other carbohydrates

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20
Q

Glucose metabolism

A

Anaerobic
- glycolytic pathway
- in cytosol
- end product is lactate
- produces 2mol ATP per mol glucose

Aerobic
- glucose -> pyruvate via glycolysis
- pyruvate -> acetyl coA via pyruvate dehydrogenase (irreversible)
- acetyl-coA enters tricarboxylic acid cycle -> energy rich molecules then used in oxidative phosphorylation
- yields 36-38mol ATP per mol glucose
- in mitochondria

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21
Q

Glycolysis

A

Converts glucose to pyruvate, in aerobic and anaerobic conditions
- double phosphorylation
= Embden-Meyerhof pathway

glucose -> glucose-6-phosphate -> fructose-6-phosphate -> F 1,6-biphosophate -> glyceraldehyde 3-P -> 1,3 diphosphoglycerate -> 3-phosphoglycerate -> 2, phosphoglycerate -> phosphoenol pyruvate -> pyruvate -> lactate

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22
Q

TCA pathway

A

Tricarboxylic acid cycle
= Kreb’s cycle / citric acid cycle

  1. acetyl coA (2C) + oxaloacetate (4C) -> citrate (6C), using citrate synthase - regulated/inhibited here
  2. citrate (6C) -> isocitrate (6C), using aconitase
  3. isocitrate (6C) + NAD+ -> ketoglutarate (5C) + CO2 + NADH + H+, using isocitrate dehydrogenase
  4. ketoglutarate (5C) + NAD -> succinyl coA (4C) + CO2 + NADH + H+, using ketoglutarate dehydrogenase
  5. succinyl-coA (4C) + GDP -> succinate (4C) + GTP, using succinyl-coA synthetase
  6. succinate (4C) + FAD -> fumarate (4C) + FADH2, using succinate dehydrogenase
  7. fumarate -> malate, using fumarase
  8. malate (4C) + NAD -> oxaloacetate (4C) + NADH + H+, using malate dehydrogenase

Citrate
Is (isocitrate)
Krebs (ketoglutarate)
Starting (succinylcoA)
Substrate (succinate)
For (fumarate)
Making (malate)
Oxacloacetate

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23
Q

Tisssues that can undergo anaerobic metabolism

Study These Flashcards
A

RBCs - no intracellular organelle, entirely depends on glucose, CANNOT use fat/ketones/amino acids
Retinal cells
Kidney medulla
Skeletal muscles

24
Q

Cori cycle

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A

Converts lactate (from anaerobic metabolism) back to glucose
In liver
Important - produces ATP and prevents build up of lactic acid

25
Features of gestational diabetes
Loss of insulin sensitivity Hyperglycaemia Increased plasma fatty acids Increased plasma ketone bodies Fetal macrosomia Increased risk of developing T2DM later Diagnosis - fasting glucose of >5.6 OR - 2hour level >7.8
26
Triglycerides
Fuel store Dehydrated = 1 molecule glycerol, 3 molecules free fatty acid Stored in adipocytes Transported by chylomicrons
27
Fatty acids
β oxidation in mitochondria Metabolized to acetyl coA Essential fatty acids - linoleic acid, linolenic acid (both unsaturated)
28
Phospholipids
Main component of cell membrane 3 groups - lecithin, sphingomyelin, cephalins
29
Ketone bodies
By-products of fatty acid metabolism (fatty acid -> acetyl coA -> ketone bodies) Synthesized in liver and kidney Consist of β-hydroxybutyrate, acetoacetic acid, acetone (excreted in urine and lung) Fuel for intermediate or prolonged starvation All (except acetone) can be converted to acetyl coA
30
Limitations of fat
Not metabolized by brain (except ketone bodies) Not metabolized anaerobically Cannot synthesize glucose
31
Adipose tissue
White - stores energy Brown - lots of uncoupled mitochondria which do not produce ATP, produces heat
32
Amino acids
2 functional groups - amine and carboxyl Acid and base at the same time Zwitterion = neutral charge amino acid ion (at certain isoelectric point the number of positive and negative charges are equal). - +ve charge from protonated amine group - -ve charge from deprotonated carboxyl group Can be precursors, eg tryptophan -> serotonin, glycine -> porphyrins, arginine -> NO, tyrosine -> L-DOPA -> dopamine and noradrenaline
33
Subclasses of amino acids
Total 20 in humans, 10 are essential - lysine - leucine - isoleucine - valine - methionine - phenalynine - tryptophan - threonine (arginine + histidine are essential dependent on age/health) Grouped into acidic, basic, aromatic, sulphydryl, imino, hydroxyl, aliphatic
34
Detoxification
1st Amino acid -> glutamic acid -> carbamyl phosphate Then urea cycle in liver: 1. mitochondria Carbamyl phosphate + ornithine -> citrulline -> arginosuccinate + aspartate 2. cytoplasm Arginosuccinate -> arginine -> urea + ornithine
35
Proteins
Polymerized amino acids, linked by peptide bonds 3 classes - globular (soluble, form enzymes), fibrous (structural), membrane (receptors) Primary structure - amino acid sequence with peptide bonds Secondary structure - 3D form of primary structure, held by hydrogen bonds Tertiary structure - overall shape of single protein molecule, held by disulphide bonds, controls basic function of protein Quaternary structure - arrangement of multiple folded protein molecules
36
Haemoglobin
1 haem ring + 4 globin rings (2α, β, γ, or δ subunits) - if α then chromosome 16 (short arm), if β then chromosome 11 (short arm) - synthesized in mitochrondira and cytosol of immature RBCs - also found in non-erythroid cells eg dopaminergic neurones in substantia nigra, macrophages, alveolar cells, kidney mesangial cells - haem is metabolised to bilirubin and cytosol of immature RBCs
37
Subtypes of Hb
Embryo - Gower 1, Gower 2, Portland Fetus - HbF (α2γ2) majority Hb by 12 weeks, 95% by birth then decline by 6months Adult - HbA (α2β2), HbA2 (α2δ2)(3%), HbF(α2γ2) Variant - HbS (sickle cell), HbC , HbH, Barts, HbE
38
Collagen
Secreted by fibroblasts and osteoblasts, from pro-collagen 4 subtypes - type 1 (bone/dermis/tendon) - makes up 50% of total body protein - type 2 (cartilage) - type 3 (fetal/cardiac/scar/synovium) - type 4 (basement membrane)
39
Classes of hormone
Endocrine/exocrine Amine-derived - catecholamines, thyroxine Peptide-derived - vasopressin, insulin, LH, FSH, TSH Phospholipid-derived (steroids) - testosterone, cortisol
40
Cholesterol
Ring-based structure 27 C atoms Transported by HDL and LDL (lipoproteins) Synthesized in endoplasmic reticulum via HMG-CoA reductase pathway Sourced from acetyl-CoA, plasma membrane cholesterol, plasma lipoproteins, intracellular lipid droplets
41
Steroids
4 rings - 3 have 6 C atoms, 1 has 5 C atoms Steroid receptors are a subclass of nuclear receptors, associated with HSP (heat shock protein) Work to increase gene transcription Hydrophobic 5 groups: Corticosteroids - mineralcorticoids (aldosterone) - glucocorticoids (cortisol) - androgen (DHEA) Gonadal - progestogens - oestrogens - androgens (testosterone)
42
Steroid synthesis
Cholesterol (C27) -> progestin (C21) -> androgen (C19) -> oestrogen (C18) Using enzymes cytochrome p450 complex, and hydroxysteroid dehydrogenase Rate limiting step is conversion of cholesterol to progestin, using enzyme cytochrome p450CSCC (cholesterol side chain cleavage) which lives in inner mitochondria Cholesterol cannot transverse aqueous space between mitochondrial membranes unaided, needs STAR (steroidogenesis acute regulatory, only in ovaries or testes) protein and PBRs (peripheral benzodiazepine receptors)
43
Cytochrome p450 complex
Variety of enzymes, including: 17-hydroxylase - catalyses pregnenolone -> 17α-hydroxy-pregnenolone -> DHEA - and progesterone -> 17α-hydroxy-progesterone -> androstenedione 21-hydroxylase - catalyses progesterone -> corticosterone - and 17α-hydroxy-progesterone -> cortisol
44
Hydroxysteroid dehydrogenase
HSD, 2 types: 3β-HSD - converts weak to strong steroid - catalyses pregnenolone -> pregnanedione, and 17α-hydroxy-pregnenolone -> 17α-hydroxy-progesterone, and DHEA -> androstenedione 17β-HSD - catalyses androstenedione -> testosterone, and oestrone -> oestradiol
45
Oestrogens
Phenol aromatic compounds 18 C atoms p450 aromatase catalyses testosterone -> oestradiol and androstenedione -> oestrone
46
Gonadal cells
Leydig cells produce testosterone, have 17β-HSD Theca cells produce androgens, does not have 17β-HSD Granulosa cells produce oestradiol, have 17β-HSD Luteal cells produce progesterone and oestradiol
47
Lipoid congenital adrenal hyperplasia
Autosomal recessive condition Due to mutations of genes for enzymes mediating the production of cortisol from cholesterol by adrenal glands - defect in 21-hydroxylase (95%), STAR protein, or cytochrome P450CSCC - so failure of steroid production and accumulation of large lipid droplets (cholesterol ester) in adrenal cortex (insufficient cortisol -> increased ACTH -> hyperplasia of adrenal cortex) Presents as ambiguous genitalia, natriuresis, precocious puberty/failure of puberty, infertility due to anovulation, virilisation, hypertension
48
Prostaglandins
Produced by all nucleated cells except lymphocytes Hydrophilic Vasomotor functions - vasoconstrictor - thromboxane, leukotriene - vasodilator - PGD, PGE2, PGF2, prostacyclin Non-vasomotor functions - PGE2 - pyrogenic, hyperalgesia, uterine contractions, increased gastric mucus, GI smooth muscle contraction or relaxation (dependent on receptor), bronchoconstriction or dilation (receptor) - PGF2 - uterine constriction, bronchoconstriction - prostacyclin - inhibition of platelet aggregation, bronchodilation
49
Prostaglandin synthesis pathway
Arachidonic acid (20C) - cyclo-oxygenase pathway -> prostaglandin H2 -> thromboxane A2, PGE2 and PGF2, prostacyclin - lipoxygenase pathway -> leukotriene
50
Prostaglandin dehydrogenase
Metabolises prostaglandins Found in lungs, ovary, testes, placenta
51
Prostaglandin receptors
G-protein receptors Seven-transmembrane domain EP receptor (PGE2) FP receptor (PGF2)
52
Clinical applications for prostaglandins
Induction of labour - PGE2, PGF2 Prevent closure of patent ductus arteriosus - PGE2 Treatment of Raynaud's, glaucoma, limb ischaemia, erectile dysfunction, peptic ulcers
53
Starvation
Obligate need to generate glucose to sustain cerebral energy metabolism (brain needs at least 25g/day) - by mobilizing glycogen stores and hepatic gluconeogenesis Initially - brain, RBCs, WBCs, renal medulla can only use glucose for their metabolism 12hours - fall in insulin, rise in glucagon, glycogenolysis in liver, muscle glycogen -> lactate then conversion in Cori's cycle to glucose 24hours - glycogen stores depleted, gluconeogenesis with protein catabolism of skeletal muscle 48hours - TAG (fat) oxidation by lipolysis, releases glycerol which can be converted to glucose and fatty acids (FAs then converted to ketones in liver) 2-3 weeks - CNS adapts to using ketones as primary fuel source to reduce muscle breakdown
54
Serum progesterone levels in diagnosis of pregnancy
NICE does NOT suggest use of serum progesterone measurements as an adjunct to diagnose either viable intrauterine pregnancy or ectopic pregnancy RCOG suggest <20nmol/l strongly suggestive non-viable pregnancy >60nmol/l suggestive intrauterine pregnancy
55
Cell organelles
Mitochondria - energy (ATP) production Golgi Apparatus - storing, packaging and modification of proteins Endoplasmic Reticulum - Rough: Protein assembly, folding & quality control - Smooth: Folding of proteins and transport in vesicles, and synthesis of lipids & role in gluconeogenesis via G6DP Nucleus - contains chromosomes, cell command centre via regulation of gene expression Ribosome - translation of mRNA into protein
56
Vitamin K
Fat soluble vitamin that is stored in the liver and adipose tissues. Other fat soluble vitamins are A, D and E. It is essential for the synthesis of: - Clotting factors (X)10,(IX) 9, 7(VII), 2 (II) = 1972 (1o, 9,7, 2) - Proteins C, S and Z - Osteocalcin and GLA proteins
57
Organelles function
Nucleus: DNA Storage Mitochondria: Energy production Smooth Endoplasmic Reticulum (SER): Lipid production; Detoxification Rough Endoplasmic Reticulum (RER): Protein production; in particular for export out of the cell Golgi apparatus: Protein modification and export Peroxisome: Lipid Destruction; contains oxidative enzymes Lysosome: Protein destruction

MRCOG Part 1 (14 decks)

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