Biochemistry Flashcards
Which cell adhesion molecule binds lymphocytes?
L-selectin
Which cell adhesion molecule binds platelets?
P-selectin
Which cell adhesion molecule binds endothelial cells?
E-selectin
When is B-hCG detectable in blood?
8 days post-fertilisation
When is B-hCG detectable in urine?
10 days post-fertilisation
Whether a miscarriage is managed expectantly or medically, when should a repeat urinary pregnancy test be performed?
Urinary pregnancy test 3 weeks later
What factors shift the oxygen dissociation curve for fetal haemoglobin to the right?
1) Increased temp
2) Increased H+
3) Increased 2,3 DPG
4) Increased pCO2
What factors shift the oxygen dissociation curve for fetal haemoglobin to the left?
1) Increasing pCO
2) Decreased temp
3) Decreased H+
4) Decreased 2,3 DPG
What are the major biochemical buffers in intracellular fluid?
1) Protein; 2) Phosphate
What is the major biochemical buffer in blood and interstitial fluid?
Bicarbonate
How much ATP does anaerobic respiration yield?
2 ATP
How much ATP does aerobic respiration yield?
30-32 ATP (traditionally thought to be 38 ATP)
What pathway converts glucose to pyruvate?
Glycolysis
Where does gluconeogenesis occur?
Liver and kidneys
What is the name of the process that produces glycogen?
Glycogenesis
What is the name of the process that produces glucose?
Gluconeogenesis
What is Northern Blotting?
Molecular genetic technique to detect RNA
What is Southern Blotting?
Molecular genetic technique to detect DNA
What is Southwestern Blotting measuring?
DNA binding proteins
What is Western Blotting?
Used in protein analysis
What is Eastern Blotting?
Used to measure protein modifications, e.g. lipids or carbohydrates
In the extracellular fluids and plasma, what is a) the main cation, b) the main anion
a) sodium; b) chloride
In the intracellular fluid, what is a) the main cation, b) the main anion
a) potassium; b) phosphate
What happens in prophase?
Chromatin condenses to chromosomes (paired as chromatids). Mitotic spindle form.
What happens in metaphase?
Chromatids align at the equatorial plane
What happens in anaphase?
Chromatids pulled apart into 2 constituent daughter chromosomes
What happens in telophase?
New nuclear envelop forms around each daughter chromosome
What happens in cytokinesis?
Cells divide
What are the DNA bases?
Adenine; guanine; thymine; cytosine
What are the RNA bases?
Adenine, guanine; uracil; cytosine
Which DNA/RNA bases pair off?
Adenine with thymine or uracil
Guanine with cytosine
Where is AFP produced in a fetus?
Principally liver, also GI tract and yolk sac
What are the subphases of mitosis?
Prophase, metaphase, anaphase, telophase, cytokinesis
What state proceeds mitosis?
Interphase
What happens in interphase, prior to mitosis?
G1 = cells increase in size S = DNA replication G2 = cells increase in size
What are the 3 types of ketone bodies?
1) Acetone
2) Acetoacetic acid
3) Beta-hydroxybutyric acid
Which of the ketone bodies can be used for energy?
Acetoacetic acid and beta-hydroxybtyric acid
When are ketone bodies produced?
In times of carbohydrate restriction. They are produced in the liver from fatty acids
What is vitamin K used for?
Synthesis of proteins C, S and Z, and clotting factors X, IX, VII and II
What is fibrinogen activated by?
Thrombin
What is the normal rate of increase of b-HCG every 48 hours?
66%
What are the causes of prolonged PT and INR?
Factor V deficiency; warfarin therapy; liver failure; DIC
What are the Ca/phosphate/ALP/PTH levels in osteoporosis?
Ca - normal
Phosphate - normal
ALP - normal
PTH - normal
What are the Ca/phosphate/ALP/PTH levels in osteopetrosis?
Ca - normal
Phosphate - normal
ALP - normal
PTH - normal
What are the Ca/phosphate/ALP/PTH levels in osteomalacia?
Ca - reduced
Phosphate - reduced
ALP - increased
PTH - increased
What are the Ca/phosphate/ALP/PTH levels in osteitis fibrosa?
Ca - increased
Phosphate - reduced
ALP - increased
PTH - increased
What are the Ca/phosphate/ALP/PTH levels in Paget’s?
Ca - normal
Phosphate - normal
ALP - increased
PTH - normal
What is the product of glycolysis?
x2 pyruvate + x2 ATP + x2 NADH
What is the rate limiting step of glycolysis?
Conversion of fructose 6-phosphate to fructose 1,6-biphosphate by phosphofructokinase
What are essential amino acids?
Amino acids that cannot be synthesised directly, and so must be obtained by diet
What are some examples of essential amino acids?
Arginine; isoleucine; leucine; lysine; trypotophan; valine
What are non-essential amino acids?
Amino acids that can be synthesised
What are some examples of non-essential amino acids?
Alanine; cysteine; glutamine; glycine; proline; serine; tyrosine
What is another name for the citric acid cycle?
The Krebs cycle
What is the start product of the Krebs cycle?
Acetyl-CoA
How is Acetyl CoA formed?
Formed from pyruvate, from glycolysis, that is then converted to Acetyl-CoA in the process of pyruvate decarboxylation by action of pyruvate dehydrogenase
What are LDLs?
Cholesterol or cholesterol esters
Transport cholesterol from liver to tissues
What are HDLs?
Collect cholesterol from cells and carried to the liver
How does insulin cause hypokalaemia?
Intracellular shifts
How does vomiting and diarrhoea cause hypokalaemia?
Loss of K+ from the body
What is the action of cytochrome P450 enzymes?
Catalyses hydroxylations
Which cell in the body are dependant on anaerobic respiration?
RBCs
Where is the chloride shift phenomenon seen?
RBCs
What is the major hydrogen ion buffer in the blood?
Haemoglobin
What food has a high vit D2 content?
Oily fish
What proportion of plasma Ca2+ is in ionised form?
45%
What is the major carrier of plasma Ca2+?
Plasma protein
What is the major production method of 2,3-DPG?
Glycolysis
What is the Hb concentration in a newborn?
17g/dL
What is the coagulation factor number for fibrinogen?
Factor I
What is the primary source of negatively charged ions in the blood?
Bicarbonate and Cl-
HbA1c is a marker of DM control over what period?
8-12 weeks
What are the biochemical findings in Paget’s disease?
Normal Ca2+
Normal phosphate
Raised ALP
How is pyruvate produced?
Glycolysis
What molecule has a major role in gene transcription?
Fatty acids
Where is AFP produced in the fetus?
Gut, liver, yolk sac
Which ketone body can be used as an energy supply for brain in starvation?
Acetoacetate
What levels of progesterone indicate a non-viable pregnancy?
15-25
What levels of progesterone indicate a non-viable pregnancy will spontaneously resolve?
<20
What levels of progesterone indicate development of a normal pregnancy in the future?
> 60
What are the biochemical findings in Conns syndrome?
Hypernatraemia
Hypokalaemia
Alkalosis
Ammonia is made from what amino acid in the kidney?
Glutamine
Where is bicarbonate reabsorbed in the kidney?
Proximal convoluted tubules
What is the main buffer in urine?
Phosphate
Which 2nd messenger signalling molecule is generated by oxytocin and stimulates Ca2+ release?
IP3
What percentage of women with a malignancy also have hypercalcaemia?
20%
Which condition is caused by a failure to mineralise newly formed osteoid?
Osteomalacia
How does pregnancy affect PTH?
Increase in PTH, calcium and calcitriol in pregnancy
Which enzyme is involved int he rate limiting step of the glycolysis pathway?
Phosphofructokinase
What hormone deficiency is characteristic of congenital adrenal hyperplasia?
Cortisol
What are the features of a salt-wasting crisis?
Vomiting, dehydration and appearing shocked
What are the hormonal imbalances that account for the salt-wasting crisis seen in 21-hydroxylase deficiency CAH?
Aldosterone and cortisol deficiency
What electrolyte imbalances may be seen in CAH?
Hyperkalaemia and hyponatraemia
Which form of CAH results in ambiguous genitalia of a genetic female due to excessive androgen exposure in the fetus?
The 21-hydroxylase deficiency form
What are the different types of CAH?
21-hydroxylase deficiency - ambiguous genitalia
11-beta-hydroxylase deficiency - hypertension (due to EXCESSIVE aldosterone)
17-hydroxylase deficiency - oligomenorrhoea and infertility
How does glucose cross the placenta?
Facilitated diffusion
Where is ALP produced?
Bone
Liver
PLACENTA
How are substances transported across the placenta?
Passive diffusion - O2, CO2, free fatty acids, urea
Active transport - amino acids
Facilitated diffusion - glucose
Endocytosis - IgG
What is the structure of fetal Hb?
x2 alpha, x2 gamma
What are the 3 types of extracellular signalling?
Endocrine - acts on distant cells via bloodstream
Paracrine - acts locally on neighbouring cells
Autocrine - acts on the cell producing the hormone
What are the 3 main classes of cell surface receptor?
- Ion-channel-linked receptors - either voltage gated or ligand gated
- Enzyme-linked receptors
- G protein-coupled receptors
What is an example of a G protein-coupled receptor?
cAMP receptors
Muscarinic receptors
What is an example of an enzyme-linked receptor?
Tyrosine kinase receptor
What are examples of ion-channel-linked receptors?
GABA receptors
Nicotinic acetylcholine receptors
5-HT receptors
What is the mechanism and action of alpha-1 receptors?
Activation of phospholipase C
Causes smooth muscle contraction, smooth muscle relaxation of the GIT and vasoconstriction of arteries and veins
What are examples of alpha-1 agonists?
Phenylephrine
Noradrenaline
What is the mechanism of alpha-2 receptors?
Inactivation of adenylate cyclase leading to decreased intracellular cAMP
What are examples of alpha-2 agonists?
Clonidine
What is the action of beta-1 receptors?
Positive chronotropic and inotropic effect on the heart, stimulates renin release
What are examples of beta-1 agonists?
Noradrenaline
Dobutamine
What is the action of beta-2 receptors?
Smooth muscel relaxation, stimulates renin release
What are examples of beta-2 agonists?
Salbutamol
Salmeterol
Terbutaline
What is the only neurotransmitter to be used at the neuromuscular junction?
Acetylcholine
What are the receptor sites of acetylcholine?
Nicotinic receptors
Muscarinic receptors
What are some examples of nicotinic agonists?
Acetylcholine
Nicotine
Suxamethonium
What are some examples of nicotinic antagonists?
Atracurium
What are some examples of muscarinic agonists?
Acetylcholine
Pilocarpine
What are some examples of muscarinic antagonists?
Atropine
Oxybutinin
Ipratropium
Where are M1 receptors found?
Exocrine glands
CNS
Where are M2 receptors found?
Heart
Where are M3 receptors found?
Blood vessels
Lungs
Salivary glands
Where are M4 receptors found?
CNS
What receptors are exclusively intracellular?
Steroid hormone receptors
Thyroid hormone receptors
Vitamin D3 receptors
What are the different types of carbohydrate?
Monosaccharides - glucose/fructose/galactose
Disaccharides - sucrose/lactose
Oligosaccharides - ABO blood group classification
Polysaccharides - glycogen
What is the obligatory glucose requirement?
2g/kg/day
How much energy does glucose provide?
4.2kcal/day
What is the brains requirement for glucose during normal food intake?
100g/day
What is the brains requirement for glucose during starvation?
25g/day
Where is glycogen stored?
Liver - stores for 24 hours
Where does anaerobic metabolism take place?
Cytosol
Where does aerobic metabolism take place?
Mitochondria
What is the process of aerobic respiration?
Glucose —> pyruvate, via glycolysis
Pyruvate —> acetyl CoA, via pyruvate oxidation
Acetyl CoA —> 36-38 ATP per molecule of glucose, via TCA pathway
What is another name for the TCA pathway?
Krebs cycle
Citric Acid cycle
What tissues can undergo anaerobic respiration?
RBC
Retinal cells
Kidney medulla
Skeletal muscle
What is the Cori cycle?
Converts lactate back to glucose
Its acts to produce glucose and prevent a build up of lactic acid
Where does the Cori cycle take place?
Liver
What is the structure of triglycerides?
1 molecule + 3 molecules of free fatty acids (FFA)
Where are triglycerides stored?
Adipose
How are triglycerides transported?
Via chylomicrons
What are the essential fatty acids?
- Linoleic acid
2. Linolenic acid
Where are ketone bodies produced?
Liver
Kidney
What are ketone bodies?
By-products of fatty acid metabolism
Fatty acid –> acetyl CoA —> ketone bodies
They are fuel for intermediate/prolonged starvation
What are the types of adipose tissues, and which type stores energy?
White and brown adipose
White adipose stores energy
What are the limitations of fats?
Not metabolised by brain (except ketone bodies)
Not metabolised anaerobically
Cannot synthesise glucose
What are the 2 functional groups of amino acid?
Amine
Carboxyl
What are the 3 classes of protein?
Globular proteins - soluble and form enzyme
Fibrous proteins - structural
Membrane proteins - receptors
What is the structure of protein?
Primary structure - the amino acid sequence held by peptide bonds
Secondary structure - 3D form, held by hydrogen bonds
Tertiary structure - overall shape, held by disulphide bonds
What is the structure of haemoglobin?
1 haem ring + 4 globulin rings
Where is haemoglobin produced?
Mitochondria
Cytsol of immature RBCs
What is haemoglobin metabolised into, and where?
Into bilurubin and carbon monoxide, by the liver
Which non-erythroid cells are haemoglobin found in?
Dopaminergic neurons in substantia nigra
Macrophages
Alveolar cells
Kidney mesangial cells
What is collagen secreted by?
Fibroblasts and osteoblasts
What are the different types of collagen?
Type 1 - bone/dermis/tendon
Type 2 - cartilage
Type 3 - fetal/cardiac/scar
Type 4 - basement membrane
How is cholesterol synthesised?
In the ER via HMG-CoA reductase pathway
What are the structure of steroids?
4 rings - 3 rings that have 6C, 1 ring that has 5C
What type of receptors are prostaglandin receptors?
G-protein couples receptors
What type of hormone are steroid hormones?
Lipid hormones
From what are all steroid hormone derived?
Cholesterol
What is the rate limiting step of steroid hormone synthesis?
Removal of the 6-carbon side chain from cholesterol (27C) to generate pregnenolone (21C)
What catalyses the reaction generating pregnenolone from cholesterol?
CYP11A1, found in the inner mitochondrial membrane
What are the mechanisms for the intracellular trafficking of cholesterol to CYP11A1?
1) StAR - steroidogenic acute regulator protein
2) Mitochondrial peripheral benzodiazepine receptors
What enzyme types are required for steroid biosynthesis?
1) CYP enzymes - catalyse the hydroxylation reactions
2) HSD enzymes - catalyse the oxidation reactions
What is the enzyme sequence required to synthesise testosterone in Leydig cells?
CYP11A1 —> CYP17A —> 3B-HSD —> 17B-HSD
What is the enzyme sequence required to synthesise androstenedione in the theca cells?
CYP11A1 —> CYP17A —> 3B-HSD
What enzyme can convert estrone to estradiol?
17B-HSD
What are the enzymes required to synthesis progesterone and estradiol in the corpus luteum?
CYP11A1 3B-HSD CYP17A CYP19 17B-HSD
Which form of oestrogen, and indeed which steroid hormone is uniquely produced by the placenta?
Estriol
What is aromatised to form estriol in the placenta?
16a-hydroxyandrostenedione
What is required for virilisation of the external genitals?
Conversion of testosterone to 5a-dihydrotestosterone by 5a-reductase
How are steroid hormones made hydrophillic so that they can be eliminated by the body?
1) CYP or HSD enzymes create a polar hydroxyl (alcohol) groups
2) Conjugating enzymes add a polar or charged chemical groups to the polar hydroxyl (alcohol) groups
What are the 4 common functional domains to steroid hormone receptors?
- Lignad-binding domain
- DNA-binding domain
- Dimerisation domain (within the ligand-binding domain)
- Transactivating factor domain
From what are all prostaglandins synthesised?
Arachidonic acid, a polyunsaturated fat
How are is arachidonic acid liberated from membranes for prostaglandin synthesis?
Action of phospholipase A2
How are prostaglandins formed from arachidionic acid?
Action of COX enzymes
What is the difference between COX1 and COX2?
COX1 is constitutively active, whereas COX2 is hormone responsive
What are the contractants of myometrial contraction?
Oxytocin and prostaglandin, by action of activating phospholipase C, leading to an increase in intracellular Ca2+
What are the relaxants of myometrial contraction?
NO, relaxin and progesterone by action cAMP and cGMP
How much weight gain during pregnancy is accounted for by a rise in intracellular fluid volume?
6-8kg
What is the acid-base disturbance that is physiological in pregnancy?
Slight respiratory alkalosis - the low pCO2 being required to maintain a diffusion gradient of CO2 across the placenta. There is a partial compensation of a HCO3- fall
When does the respiratory alkalosis in pregnancy become more pronounced?
During labour, due to maternal hyperventilation
What proportion of total body calcium is extracellular?
0.1%
What channels transport Ca2+ a) out of the gut lumen and b) out of the glomerulus filtrate?
a) TRPV6
b) TRPV5
What are the types of cells present in the parathyroid glands?
Oxyphil cells
Chief cells
What triggers the secretion of PTH?
The Ca2+-sensing receptor CaSR in response to low Ca2+
What type of receptor is CaSR?
G-protein coupled receptors
What is the major circulating form of vitamin D?
Calcidiol
What is the main action of vitamin D?
Increasing serum levels of Ca2+ and phosphate, mainly by increasing intestinal absorption
What is the 1st step in vitamin D synthesis?
Modification of 7-dehydrocholesterol to vitamin D3 (cholecalciferol), a reaction mediated by UV light in the keratinocytes
What type of receptor is the vitamin D receptor?
Nuclear receptor
What does vitamin D deficiency cause?
Children - rickets
Adults - osteomalacia
What is osteomalacia?
Failure to mineralise newly formed osteoid
How many g of Ca2+ does the fetus require?
20-30g
How much Ca2+ is required for lactation?
280-400mg/day
What is the biochemistry of primary hyperparathyroidism?
High PTH, high Ca2+, low phosphate
What are the causes of primary hyperparathyroidism?
1) Parathyroid gland adenoma(s)
2) Parathyroid hyperplasia
What is the biochemistry of secondary hyperparathyroidism?
High PTH, but low Ca2+