Biochemistry Flashcards
What are the classes of nucleic acids?
- RNA (ribonucleic acid)
- DNA (deoxyribonucleic acid)
What is the structure of DNA?
- double-stranded, double helix with a sugar phosphate backbone
- bases are joined by H bonds
What are the functions of nucleic acids (DNA, mRNA, tRNA, rRNA)?
- DNA: storage of genetic info
- mRNA: carriers of genetic info (directs translation of genetic info into proteins)
- tRNA: translator of genetic info (delivers amino acids during protein synthesis)
- rRNA: components of ribosomes (have structural and functional roles)
General structure of nucleic acids (and what is the bond that joins nucleic acids together)
- nucleic acids joined by phosphodiester bonds
- sugars: ribose (RNA), deoxyribose (DNA)
Purine bases…
Pyrimidine bases…
Bases, nucleosides, nucleotides…
Structure of tRNA…
- tRNA has a clover-leaf secondary structure
- note: RNA molecules are single-stranded
- note: Uracil instead of Thymine
What are the minimum daily intake requirements for calcium (female, male, growing skeleton, osteoporosis, and maximum)?
- female: 350mg
- male: 450mg
- growing skeleton: 750mg
- osteoporosis: 1500mg
- maximum: 3000mg
Define ‘adjusted calcium’ (laboratory test) and it’s use.
- in the blood half of the calcium is ionised and half is bound to albumin
- adjusted calcium adjusts for the amount of albumin and gives a better indication of ionised levels
- note: only ionised calcium is physiologically important
How is calcium stored in bone (what form?)? (and what is bound in bone with Ca)
- hydroxyapetite
- note: phosphate bound in bone with Ca and will also be released when bone is broken down
What effects does acidosis and alkalosis have on calcium binding to proteins?
- acidosis decreases binding
- alkalosis increases binding
What is the response to decreased circulating calcium and how does PTH act?
- caclium-sensing receptors respond and increase PTH synthesis and release from Chief cells
PTH acts in 3 ways:
- promotes Ca reabsorption via kidney
- stimulates osteoclast resorption of bone releasing Ca
- drives 1,25 vit D production in kidney which results in increased Ca absorption via the gut
What is the most common and important calcium-sensing receptor defect?
- Familial Benign Hypocalciuric Hypercalcaemia (FBHH)
- circulating calcium is elevated
What are the clinical symptoms of hypercalcaemia and what is the most common cause?
- most common cause: primary hyperparathyroidism (54%)
- stones, bones, abdominal moans, and psychic groans
What are the clinical symptoms of hypocalcaemia and what are some causes?
Symptoms:
- paraesthesia, muscle spasm, tetany, seizures, coma, Chvostek’s sign (hypersensitivty of facial nerve), Trousseau’s sign (involuntary contractions of muscles in hand/wrist), cardiac problems
Causes:
- renal failure, hypoparathyroidism, vit D deficiency/malabsorption
Trabecular (or cancellous or spongy) bone…
Cortical or compact bone…
What type of collagen is the bone matrix made out of and what are the 2 patterns in which collagen can be laid down?
- type I collagen
Can be laid down as…
- woven bone: immature form with random fibre orientation, laid down during rapid growth and fracture repair
- lamellar bone: composed of successive layers of collagen fibres with distinct orientation
Lamellar bone…
Woven bone in Paget disease…
Structure of bones…
- a shell of compact bone surrounds the medullary (or marrow cavity)
- the medullary (or marrow cavity) is the site of production of blood cells in immature animals (red marrow), but becomes progressively replaced by inactive yellow marrow, composed mainly of adipose tissue (body fat)
Structure of a child’s bone…
What is the function of osteoblasts, osteocytes, and osteoclasts?
- Osteoblasts: bone matrix synthesis (bone formation)
- Osteocytes (most abundant cells within bone): osteoblasts engulfed in bone matrix
- Osteoclasts: resorption of bone
What ratio is critical in the pathogenesis of bone diseases?
- alterations of the RANK-L / OPG ratio are critical
- RANK-L: promotes osteoclast activation by binding to RANK
- OPG: protects bone from excessive resorption by binding to RANK-L and preventing it from binding to RANK which prevents osteoclast activation
Phases of bone remodelling…
What functions do proteins have?
- structure
- metabolism
- gene regulation
- signalling
- development
Structure of an amino acid…
- all amino acids found in protein are of the L-configuration (L-isomer)
The peptide bond…
Structure of proteins…
- Primary: sequence of amino acids in a polypeptide chain
- Secondary: polypeptide chain folds to form α-helix or β-pleated sheet (joined together by H bonds)
- Tertiary: 3D shape creating subunit
- Quaternary: multiple polypeptide chains (eg. haemoglobin)
What are the 4 groups of proteins?
- Globular: compact spheres (Hb, albumin)
- Fibrous: filamentous molecule (collagen, keratin)
- Soluble: dissolve in water (Hb, immunoglobulins)
- Membrane: associated with membranes (glucose transporter)
What are the 6 main functions of enzymes?
- part of metabolic pathways (glycolysis)
- signal transduction and cell regulation (kinases, phosphatases)
- digestion (amylases, proteases)
- movement (myosin)
- energy production (ATP synthase)
- drug metabolism (monooxygenases)
What is an enzyme?
- a biological catalyst that speeds up a reaction (lowers the activation energy by providing an alternative reaction pathway) without being used up
What is Km and what does a large or small value of Km mean in terms of substrate-enzyme affinity?
- Km = a measure for the stability of the enzyme-substrate-complex (aka. the substrate concentration at which the reaction rate is 50% of the V-max)
- large Km value: low substrate-enzyme affinity
- small Km value: high substrate-enzyme affinity
What are the 3 types of sources of error in biochemistry results?
- Pre-analytical: occurs outside the lab (eg. wrong specimen collected, mislabelling, incorrect preservative)
- Analytical: error within the lab (eg. human or instrumental error)
- Post-analytical: correct result is generated but is incorrectly recorded in patients records (eg. transcription error)
Sensitivity VS specificity…
- Sensitivity: measure of number of false negatives (n)
- Specificity: measure of number of false positives (p)
what are the 5 classes of lipids?
- fatty acids
- triacylglycerols/triglycerides (fats and oils)
- glycerolphospholipids (membrane lipids)
- sphingolipids (membrane lipids)
- cholesterol
What is an unsaturated fatty acid?
- contains carbon-carbon double bond(s)
Fatty acid general formula?
Explain cis-configuration (cis and trans isomers)
What is the relationship between fatty acid melting points and the number of double bonds?
- as number of double bonds increases, the melting point decreases
What is the relationship between fatty acid melting points and the number of carbon atoms?
- as number of carbon atoms increases, the melting point increases
What transports triacylglycerols (triglycerides) and where are they stored?
- transported by lipoproteins
- stored in adipocytes
What are triacylglycerols (triglycerides) made up of?
- glycerol and fatty acids
If the body needs energy, how are triacylglycerols (triglycerides) broken down and what into?
- broken down by hormone-sensitive lipase (lipolysis)
- into glycerol and fatty acids
What type of lipoprotein transports diet triglycerides from the intestine to fat tissue and liver?
- chylomicrons
describe the structure of cholesterol
- weakly amphiphilic (has both hydrophilic and hydrophobic parts)
- condensed 4 ring system (steroid ring system)
what is the source of cholesterol and where is it synthesised?
- from diet
- synthesised in liver
what is the precursor molecule for bile acids, glucocorticoids (eg. cortisol), vitamin D3, mineralocorticoids (eg. aldosterone), progestogens (eg. progesterone), androgens (eg. testosterone), and estrogens (eg. estrone)?
- cholesterol!
in what form do carbohydrates have to be in to be absorbed?
- monosaccharides
why are carbohydrates important (functions)?
- energy source
- energy storage
- structural component
- immune function
- intercellular communication
what is the general formula of carbohydrate?
-
how are monosaccharides classified?
- by their functional group…
- Aldoses (has aldehyde functional group): eg. glucose
- Ketoses (has ketone functional group): eg. fructose
what is an isomer?
- compounds that have the same chemical formula but different structural formula
what are the main functions of glucose?
- energy source
- required energy source of cells with few or no mitochondria
- (essential in existing muscle)
what are some sources of fructose?
- fruits, vegetables, honey
what are some sources of galactose?
- dairy products
what are the components of sucrose, maltose, and lactose? (and what is the chemical bond between the two monosaccharides?)
- glucose + fructose = sucrose
- glucose + glucose = maltose
- galactose + glucose = lactose
- (glycosidic bond)
what is the storage polysaccharide in animals?
- glycogen
what is the structure of glycogen?
- branched polymer
- mainly α (1→4) linkages, branches α (1→6) linkages
describe the absorption of carbohydrates
- the released monosaccharides are absorbed by intestinal mucosal cells (in the duodenum and upper jejunum)
- glucose and galactose are absorbed by sodium-dependent glucose cotransporter 1 (SGLT-1)
- fructose is absorbed by sodium-independent monosaccharide transporter (GLUT-5)
- then, all three monosaccharides are transported from the intestinal cells into circulation by GLUT-2
What is the cause of lactose intolerance?
- patient cannot digest lactose (doesn’t have enzyme lactase)
what are the symptoms of lactose intolerance?
- undigested carbohydrate will pass into the large intestine and causes osmotic diarrhoea
- bacterial fermentation of carbohydrate produces large volumes of CO2 and H2 which causes abdominal cramps, diarrhoea, and flatulence
how is lactose intolerance managed?
- diet (avoid lactose)
- enzyme replacement therapy (patient takes lactase)
what is galactosaemia?
- genetic disorder that affects the ability to metabolise galactose
- the accumulation of galactose is then oxidised (galactonate) and reduced (galactitol) to toxic metabolites
- (only treatment is elimination of lactose and galactose from diet)
Metabolism of glucose…
What are the clinical features of vitamin D deficiency?
- non-specific
- fatigue
- generalised MSK pain and hyperalgesia (increased sensitivity to pain)
- muscle weakness (myopathy), difficulties rising from sitting position
- waddling gait
- fragility fractures
what are 3 ways in which one can increase their vitamin D intake?
- sunlight exposure
- food (oily fish)
- supplements
What type of vitamin D do you get from sunlight exposure, foods, and supplements?
- Calciferol (or vitamin D2)
What type of vitamin D is the reserve supply found in the blood plasma?
- Calcidiol (25 hydroxy vit D)
What type of vitamin D is the active form (active hormone)?
- Calcitriol (1,25 vitamin D3)
What are the functions of Calcium?
- Provides stiffness and structure in bones
- Regulatory functions (neurotransmission, reproduction, hormone action, cellular growth, enzyme function)
What are some factors which affect intestinal calcium absorption?
- Intake of vitamin D and calcium
- Age (older you are the less you absorb)
- Physiological state (growth, pregnancy)
- GI disorders
What are some sources of calcium (food)?
- Dairy products
- Cereals
- Green leafy vegetables
What are some sources of vitamin D?
- Skin synthesis (sun exposure)
- Diet (oily fish, eggs, cereals)
- Supplements
What are some causes for calcium deficiency?
- Low supply (low dietary intake)
- Low absorption (vitamin D deficiency, GI disorders)
What are some causes for vitamin D deficiency?
- Low intake (sun exposure, diet)
- Low absorption (GI disorders with fat malabsorption)
- Obesity (vitamin D sits in fat tissue and is not available to liver and kidney)
What is measured to assess vitamin D status?
- Plasma 25-hydroxyvitamin D (25 OH D)
- (not 1, 25 vit D!)
NICE and royal osteoporosis society guidance for vitamin D thresholds
- <25 nmol/l: deficient
- 25-50 nmol/l : insufficient
- > 50 nmol/l: sufficient for most
What are some risk factors for vitamin D deficiency?
- Darker skin
- Low UVB exposure
- Exclusively breastfed babies (little vitamin D in breast milk)
What are the clinical features of Rickets (children’s form of vit D deficiency)?
- Associated with osteomalacia
- Muscle weakness
- Bone pain
- Cardiomyopathy
- Hypocalcaemic fits
What biochemistry markers should be checked for a child with suspected Rickets?
- Blood: plasma 25 vit D, Ca (albumin adjusted), PTH, bone alkaline phosphatase
- Urine: calcium and phosphate
Describe the structure of connective tissue.
- highly specialised tissues
- provide mechanical support and assist in movement
- matrix around cells regulates their behaviour (how the cell interacts/binds with things, eg. growth factors)
- may contain blood vessels, nerves
- arena for fighting infection
- diverse structure and function, but composed of same building blocks
Describe the different classes of hormones
- Peptide hormones (large - all pituitary and insulin)
- Amino acid derived (adrenaline, dopamine, thyroxine)
- Steroid (end in -one or -ol, testosterone, oestradiol, cortisol)
Describe two mechanisms by which hormones work at cellular level
- Membrane-bound: eg. water-soluble
act through a receptor on cell surface via a G protein and have various actions (eg. phosphorylation, activate kinases, open ion channels) - Intracellular: eg. pass through cell wall, lipid based hormones (act intracellular, eg. in cell nucleus)
Which hormones work through neurones rather than blood borne?
Hypothalamic hormones stimulating the posterior pituitary by carrier proteins known as neurophysin granules
- this is known as interaxonal transport (oxytocin and vasopressin transported and released in the posterior pituitary)
Calcium homeostasis video…
- Dr Matt and Dr Mike: calcium homeostasis (PTH and vit D)
Vitamin D video…
Dr Matt and Dr Mike: vitamin D
Glycolysis video (watch video, draw out pathway)…
- Khan academy: overview of glycolysis
Pentose phosphate pathway video (watch video, draw out pathway)…
- Khan academy: pentose phosphate pathway
What is glycolysis and where does it take place?
- the breakdown of glucose, produces 2 ATP, 2 NADH, and 2 pyruvate
- metabolic pathway that occurs in the cytosol of the cell (same place as pentose-phosphate pathway)
What processes occur to breakdown glucose, why do we want to break it down, and where does it occur?
- glycolysis, Krebs cycle (or citric acid cycle), electron transport chain
- end goal is to produce ATP
- occurs in the cytosol of the cell
Is any ATP produced in the pentose-phosphate pathway?
- no
What is oxidisation?
- the loss of electrons
What is the start product of the oxidative phase of the pentose-phosphate pathway?
- glucose-6-phopshate
What is the start product of the non-oxidative stage of pentose phosphate pathway?
- ribulose-5-phosphate
What are the end products of the pentose phosphate pathway?
- ribose-5-phosphate (important for DNA and RNA synthesis)
- NADPH (donates electrons, important for anabolic reactions, eg. synthesis of fatty acids, and anti-oxidants)
Which phase of the pentose phosphate pathway (oxidative or non-oxidative) is irreversible?
- the oxidative stage is irreversible
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Carbohydrate metabolism quiz Q1…
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