Biochemistry Flashcards
Components of the nucelosome
DNA wrapped around a large histone
H1 histone linker connects them
DNA negative with phosphate groups
Histone are LARGe and positive from lysine and arginine
What is heterochromatin
Highly condensed (HeteroChromatin)
Dark, less visible on EM
Deactivates transcription
What is Euchromatin
Euchromatin is expressed
Active, more visible on EM
Transcriptionally active
What is visible and non-visible on EM stain
Euchromatin visible
Heterochromatin less visible (dark)
Function of DNA methylation
Adds methyl groups to DNA which changes the expression of DNA without altering the sequence
Deactivates DNA
Condition with dysregulated DNA methylation
Fragile X syndrome
What is histone acetylation
Acetylation makes DNA active
Activates transcription
What is histone deacetylation
Removal of acetyl groups - deactivates DNA, by reducing transcription
What condition is associated with histone acetylation
Thyroid fisorders
Thyroid hormone synthesis can be altered by acetylation
What condition is associated with histone deacetylation
Huntingtons disease
What amino acids are purine and pyramidines
Purines - A, G
Pyramidines - C, U, T
Deamination reaction of;
Guanine, cytosine, 5 methylcystine, adenine
Cystosine - uracil
Guanine - xanthine
Adenine - hypoxanthine
5 methylcystine - thymine
Drugs that affect pyramidine synthesis
Leflunomide - dihydrooate dehydrogenase
5- flurouracil - thymidylate synthesis
Drugs affecting purine synthesis
5 mercaptopurine - de novo purine synthesis
Mycophenalate and ribavirin - inosine monophosphate dehydrogenase
Drugs that affect both purine and pyramidine synthesis
Methotrexate, TMP, pyramethamine - dydrofolate reductase
Hydroxyurea - ribonucleotide reductase
Condition caused by impaired nucleotide excision repair
Xeroderma pigmentosum
Types of DNa repair and where they occur in the cell cycle
Nucleotide excision repair - G phase
Base excision repair - throughout
Mismatch repair - S phase
Condition caused by impaired DNA repair - non homologous end joining
Ataxia telangectasis
Condition caused by impaired DNa repair - homologous recombination
BRCA 1 and 2 + fanconi syndrome
Function of helicase
Helicase halves DNA at replication fork
Function of primase
Primes RNA for DNA to initiate replicarion
Function of telomerase
Adds TTAGGG to avoid loss of materal with duplication
Telomerase TAG’s for Greatness and Glory
Types of DNA repair
Single stranded
- nucleotide excision repair (G phase)
- base excision repair (throughout)
- mismatch repair (S phase)
Double stranded
- homologous recombination
- non-homologous end joining
What is a transition mutation
Purine - purine or pyramidine to pyramidine change
Silent mutation
Same codon
Missense mutation
Changed amino acid
Nonsense mutation
Stop in codon, non functioning protein
Condition caused by missense mutation
Sickle cell
Conditjons caused by frameshift mutation
Cystic fibrosis, taysaxhs, duchenne muscular dystrophy
Conditiond caused by splice site mutation
Marfans, beta thalassaemia, gauchers
RNA polymerases - eukaryotes
RNA polymerase I - rRNA
RNA polymeraze II - mRNA, miRNA, snRNA
RNA polymerase III - tRNA, 5s RNA
rNA MIght Maintain Small Nucleus by 5pm Tonight
RNA polymerases - prokaryotes
1 RNA polymerase - all kinds of
Sequence of protein synthesis
Initiation - elongation - termination
What are the 2 types of post translational modifications
Trimming
Covalent alterations
Trypsinogen to trypsin is what type of post translational modification
Trimming
Phosphorylation is what type of post translational modification
Covalent alteration
pathophysiology of Lesch Nyhan syndrome
defective purine salvage (utilizes folate/vitamin D)
absent HGPRT
features of lesch nyhan syndrome
caused by absent HGPRT
Hyperuriciaemia
Gout
Pissed off (self mutilation)
Rred/orange crystals in urine
Tense muscles (dystonia)
also megaloblastic anaemia due to low folate and b12
phases of the cell cycle are regulated by what?
cyclins, cyclin dependant kinases, and tumour suppressor genes
where does n-linked glycosylation occur?
rough endoplasmic reticulum
‘N-linked eNdoplasmic’
function of rough endoplasmic reticulum
site of synthesis of secretory (exported) proteins, N-linked oligosaccharides, lysosomal and other proteins
function of smooth endoplasmic reticulum
site of steroid synthesis and detoxification of drugs and poisons
‘gets rid of bad stuff to make it smooth and nice’
(lacks surface ribosomes which makes it smooth)
what cells are rich in smooth endoplasmic reticulum?
hepatocytes and steroid hormone producing cells of the adrenal cortex and glands
(function is for steroid synthesis and detoxification of drugs and poisons)
what are the vesicular tracking proteins
carry material from ER to golgi appartatus or from golgi to ER
COPI - retrograde (golgi to ER)
COPII - antegrade (ER to golgi)
2 steps forward, 1 step back
clathrin - trans golgi
pathophysiology of adrenoleukodystrophy
x-linked recessive disorder of beta-oxidation due to mutation of the ABCD1 gene of peroxisomes
results in a build of VLCFA in adrenal glands
what type of immune responses are proteasomes responsible for?
MHC-1 mediated
function of cystoskeleton filaments;
microfilaments
intermediate filaments
microtubules
microfilaments - muscle contraction
intermediate filaments - maintains cell structure
microtubules - movement, cell division
pathophysiology of primary cilliary dyskinesia
autosomal recessive
Dynein arm defect
features of primary ciliary dyskinesia
situs inversus
hearing loss
recurrent chest infections
infertility - ectopic pregnancys
how does digoxin affect ATP pump
inhibits atp pump so directly inhibits Na/Ca exchange resulting in increased Ca = increased cardiac contractility
Na and K movement in Na/K Atp pump
3 K in
2 Na out
4 types of collagen and where each are most commonly found
1 - skeletal, skin, tendon, Late wound repair
2 - cartillage, vitreous humour
3 - arteries, skin, uterus, foetal, Early wound repair
4 - basement membrane (glomerulus, cochlea), lens
5 - interstitial tissue, placenta
what type of collagens are involved in early and late wound repair
early type 3 collagen
late type 1 collagen
type of collagen affected in ehlors danlos syndrome
classical type (skin and joint symptoms) -> type V
vascular type (SAH, aneurysms) -> type III
whats the genetic term to describe the BRCA 1gene
incomplete penetrance
(not everyone with the BRCA1 gene will develop ovarian or breast cancer)
whats the genetic term to describe huntingtons disease
anticipation
increased severity or earlier onset with each succeeding generation
what is allelic heterogenicity and a condition it is found in
different alleles in the same locus result in the same disease
beta-thalassaemia
what conditions are an example of imprinting
prader willi and angleman syndrome
in prader willi, disease occurs when maternal or paternal derived gene is silenced or mutated?
paternal
in angleman syndrome, disease occurs when maternal or paternal derived gene is silenced or mutated?
maternal
chromosome involved in prader willi and angleman syndromes?
chromosome 15
chromosome affected in haemochromatosis
6
chromosome affected in ADPKD and huntingtons
4
chromosome affected in renal cell carcinoma and von hippel lindau
3
chromosome affected in williams syndrome and CF
7
chromosome affected in wilsons disease and patau syndrome
13
what chromosome is affected in FAP
5
chromosome affected in BRCA 2
13
chromosome affected in marfans syndrome
15
what part of the brain is affected in wernickes-korsakoffs syndrome
dorsal nucleus of thalamus
FAD and FMN are derived from what vitamin
B2 (riboflavin)
NAD and NADP are derived from what vitamin
B3 (niacin)
what vitamin is a component of coenzyme A (COA)
B5
what vitamin is a component of pyridoxal phosphate (PLP)
pyridoxine (B6)
features of zinc deficiency
delayed wound healing
suppressed immunity
male hypogonadism
reduced adult hair
anosmia
acrodermatitis enteropathica (occurs at openings i.e. perianal)
antedote for alcohol overdose and mode of action
fomepizole
(competitive inhibitor of alcohol dehydrogenase)
mode of action of disulfiram
inhibits acetaldehyde deydrogenase which increases acetaldehyde = increased hangover symptoms
resting phase of cell cycle
G0
what phase of the cell cycle determines the length of the cycle
G1 phase
what phase of the cell cycle is the shortest
mitosis
what phase of the cell cycle does DNA, RNA and histone synthesis occur
S phase
what are the 2 main regulators of Ca in the body
PTH and calcitriol (active form of vit D)
what enzyme is responsible for the phsophorylation of glucose to glucose-6-phosphate
glucokinase
rate limiting enzyme of glycolysis
phosphofructokinase-1 (fructose-6-P to fructose-1,6,biphosphate)
glucokinase/hexokinase (glucose to glucose-6-P)
rate limiting enzyme of cholesterol synthesis
HMG-COA reductase
rate limiting enzyme of ketogenesis
HMG-COA synthase
rate limiting enzyme of lipolysis (fatty acid oxidation)
carnitine acyltransferase I
rate limiting enzyme for HMP shunt (hexose monophosphate shunt)
glucose-6-phosphate dehydrogenase
vitamin C is responsible for production of what proteins and enzyme?
proline and lysine in collagen synthesis
dopamine beta-hydroxylase (dopamine to NE)
what vitamin helps absorption of iron suplements?
ascorbic acid (vit C)
NAD and NADP are derived from what vitamin ?
are they used in anabolic or catabolic processes ?
vitamin B3 (niacin)
NAD - catabolic
NADP - anabolic (fatty acid and steroid synthesis)
function of glucokinase and where is it found
converts glucose to glucose-6-phosphate
found in liver
hexokinase converts this in other tissues
what enzyme catalyses glucose to glucose-6-phosphate
glucokinase in liver and b cells in pancrease
hexokinase in other tissues
feedback inhibitor for glucokinase and hexokinase
both convert glucose to glucose-6-phosphate
glucokinase inhibited by fructose-6-phosphate
hexokianse inhibited by glucose-6-phosphate
is glucosekinase and hexokinase induced by insulin
glucoskinase yes
hexokianse no
does PFK or FBP increase during gluconeogenesis?
FBP increases in gluconeogenesis
PFK decreases
FaBien the Peasant works hard when starving
Prince FederiK only works when fed
what cofactor does arsenic inhibit ?
what is the function of this cofactor ?
lipoic acid
cofactor for 3 enzymes in the mitochrondri that link glycolysis to TCA cycle
cofactors required in the pyruvate dehydrogenase complex in the mitochondria
(pyruvate +NAD +CoA -> NADH + acetylCoA + C02)
The Lovely Coenzymes For Nerds
Thiamine (B1)
Lipoic acid
CoA (B5 pantothenic acid)
FAD (B2 riboflavin)
NAD (B3 niacin)
in pyruvate dehydrogenase deficiency, what lab serum lab finding would there be?
increased serum alanine
gluconeogenesis irreversible enzymes
pathway produces fresh glucose
pyruvate carboxylase
phosphoenolpyruvate carboxylase
fructose-1,6, biphosphatase 1
glucose 6 phosphate
main inhibitory neurotransmitter in the brain
GABA (glycine in spinal cord)
main inhibitory neurotransmitter in the spinal cord
glycine (GABA in brain)
Glycine can be synthesised from what essential amino acid
serine
glycine causes inhibition through what receptors
NMDA (prevents glutamate-mediated depolarisation via NMDA receptors at post synaptic terminal)
glycine is used as an intermediate in the synthesis of what proteins
porphyrins and purines
G-6-P deficiency results in a build up of what amino acid
glutathione
features of hartnup disease
rare secondary form of pellagra
sun exposed dementia
diarrhoea
dementia (incl nystagmus, ataxia, )
hartnup disease results in elevated level of what amino acid in the urine
tryptophan (due to reduced abroption in the kidney and gut)
hartnup disease results in what vitamin deficiency
niacin (B3) due to tryptophan deficiency
