MCBG Flashcards
Essential amino acids
If Learned This Huge List May Prove Truly Valuable Conditionally essential AA: cysteine, tyrosine, arginine Isoleucine Lysine Tryptophan Histidine Leucine Methionine Phenylalanine Threonine Valine
Essential vitamins and deficiencies
Fat soluble vitamins: A: deficiency causes xeropthalmia D: rickett’s/osteomalacia E: neurological abnormalities K: defective blood clotting
Water soluble:
B12: anaemia
C: scurvy
Lactose intolerance types
Primary lactase deficiency: absence of lactase persistence allele
Secondary lactase deficiency: caused by injury to small intestine (gastroenteritis, coeliac disease, Crohn’s disease, ulcerative colitis) is usually reversible
Congenital lactase deficiency: Very rare, autosomal recessive defect in lactase gene hence cannot digest breast milk
Glucose transporters
Glut1: adult erythrocytes, fetal tissues, BBB
Glut2: small intestine, kidney, liver, pancreatic beta cells
Glut3:neurones, placenta
Glut4: adipose tissue, striated muscle (insulin regulated)
Glut5: intestine, spermatozoa
Glycolysis enzymes
Hexokinase, phosphofructokinase-1* (key rate controlling enzyme), pyruvate kinase
Glycerol phosphate role
Converted from glyceraldehyde-3-phosphate, required for triglyceride and phospholipid synthesis
Enzyme= glycerol 3-phosphate dehydrogenase
2,3 bisphosphoglycerate role
Reversible reaction to form 1,3 bisphosphoglycerate
Produced in rbc, regulates O2 affinity (promotes release)
Enzyme= bisphosphoglycerate mutase
Fructose metabolism issues
Essential fructosuria: lack fructokinase so fructose not digested and excreted
Fructose intolerance: aldolase B missing, Fructose-1-phosphate accumulates leading to liver damage, treatment=remove fructose from diet
Galactosaemia symptoms + causes
Deficiency in galactokinase, uridyl transferase or UDP-galactose epimerase
Galactose accumulation leads to galactitol production via aldose reductase, more NADP+ produced, innapropriate disulphide bond formation, loss of integrity of some proteins e.g lens of eye (cataracts)
Significance of pentose phosphate pathway
Glucose-6-phosphate exits glycolysis, forms ribose-5-phosphate required for DNA, RNA, coenzymes
Occurs in cytosol, can re-enter glycolysis
Forms NADPH (IMPORTANT AS G-6-P DH DEFICIENCY CAUSES OXIDATIVE STRESS, HEINZ BODIES, HAEMOLYTIC ANAEMIA) and CO2
Glucose-6-P -> 5c sugar+ CO2 (forms NADPH, catalysed by GLUCOSE-6-P DEHYDROGENASE)
Glycolysis points of regulation
Metabolic regulation: ^[ATP] inhibits PFK, ^[NADH] inhibits step 6
Hormonal activation: ^ by high insulin:glucagon ratio
Hexokinase allosterically inhibited by glucose-6-phosphate
Pyruvate dehydrogenase roles
(Essentially link reaction)
Multi-enzyme complex catalyses pyruvate+ coA-> acetyl coA
Irreversible reaction hence key regulatory step
PDH deficiency leads to lactic acidosis
Reaction is sensitive to vit B1 deficiency
Fatty acid metabolism key points
TAG packaged in chylomicrons and absorbed through small intestine
FA activated (links to coA outside mitochondrion)
Moved through inner mitochondrial membrane via cartinine shuttle
Beta oxidation forms acetyl coA, acetyl coA enters krebs or…
Acetyl coA converts to HMG coA and then (Well fed state) converts to mevalonate, then cholesterol using HMG coA reductase
(Starved state) converts to actoacetate (+other ketones) via HMG coA lyase
3 main ketones, use+production
Acetone
Acetoacetate
Beta hydroxybutyrate
Ketones produced in liver, spare glucose usage in starvation for glucose requiring cells, are either metabolised or converted into cholesterol
HMG coA lyase converts HMG coA into ketones, HMG coA reductase converts HMG coA into cholesterol
Enzyme regulation mechanisms
Isoenzymes- different AA sequence but catalyse the same reaction
Allosteric regulation- T state= low affinity, R state= high affinity, binding away from active site leads to conformational change
Regulation of clotting
- Inactive zymogens present at low conc
- Proteolytic activation leads to amplification by cascade
- Clotting factors cluster, thrombin causes feedback activation- coverts fibrinogen to fibrin
- Termination of clotting- multiple mechanisms, regulated by proteolytic activation
Collagen synthesis
- Cleavage of signal peptide
- Hydroxylation of proline+ lysine molecules
- Addition of N linked oligosaccharides and galactose in ER
- Disulphide bond formation
- Procollagen transported to Golgi
- O-linked glycosylation in Golgi
- Golgi- exocytosis as tropocollagen
- Removal of N and C terminal propeptides
- Lateral aggregation to form fibrils
Where are the DNA checkpoints? What repair is undertaken?
Gap phase 1+ Gap phase 2+ mitosis
Base excision repair, mismatch repair, nucleotide excision repair, recombinational repair
Centromere locations
P arm= short, Q arm= long
Metacentric= central Submetacentric= close to central Acrocentric= P arm is very short Telocentric= centromere is at telomere
Gamete production/ derivatives
Spermatogonium-> primary spermatocyte-> spermatids-> mature sperm
Oogonium-> primary oocyte-> polar bodies-> 1 mature ovum
Genetic disease examples
Autosomal recessive- cystic fibrosis
Autosomal dominant- Huntington’s disease
X-linked recessive- haemophilia A (all males affected, inherited from mother)
X-linked dominant- fragile X syndrome
Y-linked- colour blindness (only males affected- linked to ‘maleness’)
Mitochondrial- mitochondrial myopathy (inherited from mother)
Transcription+ translation
Transcription initiation- DNA sequence read 3’ to 5’, catalysed by RNA polymerase, transcription factors bind to promoter
Translation- capping (5’ cap), splicing (removal of introns, exons joined by spliceosomes), tailing (3’ polyA tail)
What happens to Lineweaver-Burke plot with addition of inhibitors?
Linear graph
Addition of competitive inhibitor: gradient increases, x intercept moves right
Addition of non-competitive: x intercept doesn’t change, gradient increases
Glucose dependant cells
Red blood cell (erythrocytes)
Neutrophils
Lens of eye
Innermost cell of kidney medulla
Molecular techniques
FISH: fluorescent in situ hybridisation, used to detect aneuploidy etc, label w/ fluorescent dye then denature and hybridise
Southern blotting: DNA hybridisation+ gel electrophoresis, uses probes, investigate gene structure
Microarray: many genes analysed simultaneously, monitors change in gene expression
SDS PAGE: protein gel electrophoresis, separates proteins based on size
Agarose gel electrophoresis: separates DNA based on size/shape
PCR: analyses small changes in DNA sequence, primer annuals to sequence, taq polymerase replicates, heated + cooled to replicate
