Biochemistry 3.0 Flashcards
what is the function of glucose-6-phosphate in the HMP shunt
G6P reduces NADP to NADPH which in turn reduces glutathione via glutathione reductase. GSH - the reduced form of glutathione protects against oxidative stress
therefore in G6P deficiency, glutathione is not reduced to GSH so theres no protection
will result in raised levels NADP and glutathione but low NADPH and GSH
features of porphyria cutanea tarda
tea coloured urine
chronic but mildly elevated transaminases
bullae/blistering of skin exposed areas of skin
defective enzyme in porphyria cutanea tarda and where this is found in the cell
UROD enzyme found in the cytoplasm
what co-factor does aminolevulinate synthase require
pyridoxine B6
what would a deficiency in aminoleuvilinate synthase may cause
sideroblastic anaemia and cheilosis
what would a deficiency in homocysteine methyltransferase cause
megaloblastic anaemia
co factor for homocysteine methyltransferase
vitamin B12
what cofactor does pyruvate carboxylase require
biotin B7
what cofactor does alpha-ketoglutarate dehydrogenase cause
vitamin B12
what would a deficiency in alpha-ketoglutarate dehydrogenase cause
wernickes encephalopathy
pyruvate dehydrogenase deficiency would cause a build up of what substances
lactate (vie LDH) and alanine (via ALT)
features of pyruvate dehydrogenase deficiency
results in a build up of pyruvate which gets shunted to lactic acid (via LDH) and alanine (via ALT)
causes neurological defects, lactic acidosis and rise in serum alanine in infancy
treat with ketogenic diet (high fat content, high lysine and leucine), B1 and lipoic acid
a diet high in what amino acids should be in a patient with pyruvate dehydrogenase deficiency
leucine and lysine
conditions with defect in breakdown of glycosaminoglycans
hurler and hunter syndromes
(mucopolysaccharides in urine)
conditions with defect in metabolism of essential amino acids
maple syrup disease (alpha ketoacids)
phenylketonuria (phenylketones)
condition with defect in protein tagging at the golgi apparatus
I-cell disease
bleeding disorder with elevations of both PT and APPT with history of prolonged exposure to antibiotics
vitamin K deficiency (defect in carboxylation of glutamic acid residues by glutamyl carboxylase)
what vitamin is required to activate vitamin K dependant clotting factors
vitamin C
hydroxylation of proline residues requires what coenzyme
vitamin C
enzymes affected in lead poisoning
ferrochelatase + aminolevulinate dehydratase
(required enzymes in haem synthesis = microcytic anaemia)
lead poisoning causes a build up of what substances
aminovulinate and protoporphyrin
converts ganglioside M2 to ganglioside M3
tay-sachs (hexosaminase deficiency)
converts glucocerebroside to ceramide
gauchers (beta-glucocerebrosidase deficiency)
converts galactocerebroside to ceramide
krabbes (galactocerebrosidase deficiency)
ceramide trihexoside to lactosyl cerebroside
fabrys (alpha galactosidase deficiency)
classic galactosaemia results in a rise of what substances
galactitol and galactose-1-phosphate
caused by defieincy in the enzyme GALT
jaundice, hepatomegaly, failure to thrive
what is the main component of surfactant
phosphatidylcholine ‘lecithin’
what type of pneumocytes is surfactant produced from
type 2 pneumocytes (cuboidal, columnar)
features of maple syrup disease
impaired breakdown of alpha ketoacids (Leucine, isoleucine and valine) due to deficient apha ketoacid dehydrogenase
Alpha ketoacids in urine
presents with sweet smelling urine, poor feeding, hypo/hypertonia, vomiting
features of pompes disease
due to alpha 1,4 glucosidase deficiency
hypotonia, hepatomegaly, macroglossia, heart murmur, cardiomegaly
what is the rate limiting step of glycolysis
phosphofructokinase
what substance inhibits the rate limiting step of glycolysis
citrate –> this will reduce production of pyruvate from glucose
what is a precursor to thyroid hormone
tyrosine –> phenylalanine
deficient enzyme in PKU
tetrahydrobiopterin (co-factor for Phenylalanine hydroxylase)
malignant PKU –> DHPR
the deficient enzyme in McArdles is found in what part of the cell
cytosol
what vitamin K clotting factor has the shortest half life
vitamin VII
how do non-competitive inhibitors affect Km and VMAX
non-competitive inhibitors decrease VMAX but no effect on Km
(decreased reaction rate (vmax) but no effect on affinity)
how do competitive inhibitors affect Km and VMAX
compeitive inhibitors increase Km but no effect on VMAX
(decreased affinity but no change in
what type of inhibitor can be overcome by increasing concentration of substrate
comptitive inhibitors
infantile cataract with hepatomegaly
(glucose-1-phsophate uridyltransferase GALT deficiency) classic galactosaemia
infantile cataracts without hepatomegaly
galactokinase deficiency
what motor protein is involved in retrograde transport
dynein (within microtubules)
what motor protein is involved in antegrade transport
kinesin (within microtubules)
what effects would a deficiency in glutamate decarboxylase cause
glutamate decarboxylase converts glutamate to GABA which is responsible for inhibiting neurotransmitters in the brain = increased seizure activity/neuro excitability
what vitamin protects cell membranes from oxidative damage
vitamin E
vitamin deficiency responsible for angular cheilitis
vitamin B2 (riboflavin) (derived from FAD and FMN)
what electron carried is used in steroid synthesis
NADPH
describe how intoxication of ethanol can cause hypoglycaemia
NAD is converted to NADP during ethanol metabolism.
the resulting increase in NADP:NAD ratio in the liver leads to inhibition of gluconeogenesis and resulting hypoglycaemia
where in the cell is insulin synthesised
rough endoplasmic reticulum
describe pathophysiology of chronic granulomatous disease
CGD is caused by a lack of NADPH oxidase, a key enzyme used by neutrophils to destroy pathogens via respiratory burst.
NADPH oxidase uses oxygen as a substrate to produce superoxide anion, which is used to generate hydrogen peroxide and ultimately hypochlorous acid.
what substrate is required for the deficient enzyme in chronic granulomatous disease
oxygen is the substrate for NADPH
rate limiting step of urea cycle
carbomyl phosphate synthesis
rate limiting step of glycogenolysis
glycogen phosphorylase
rate limiting step of ketogenesis
HMG CoA synthase
rate limiting step of lipolysis (breakdown of adipose tissue to fatty acids)
hormone sensitive lipase
rate limiting step of fatty acid oxidation
carnitine acetyltransferase
rate limiting step of fatty acid synthesis (lipogenesis)
(citrate shuttle)
acetyl CoA carboxylase
rate limiting step of HMP shunt
glucose-6-phosphate dehydrogenase
what type of channel receptors are used in myaesthenia gravis
Ligand gated ion channels
what is a co factor in the synthesis of GABA
pyridoxine (B6)
where in the cell does beta oxidation of fatty acids occur
b oxidation is the breakdown of fatty acids
occurs in mitochondria
long chain fatty acids are transferred to the mitochondria via what shuttle? what is the rate limiting enzyme?
carnitine shuttle
carnitine acetyltransferase
where in the cell does fatty acid synthesis take place
cytosol
role of malonyl CoA in fatty acid oxidation
inhibits carnitine acetyltransferase therefore inhibiting fatty acid oxidation
role of citrate and palmitoyl CoA in fatty acid synthesis
citrate activates fatty acid synthesis (via activation of acetyl CoA carboxylase)
palmitoyl CoA inhibits
rate limiting step of glycolysis
phosphofructokinase-1
rate limiting step of gluconeogenesis
fructose-1,6- biphosphate
rate limiting step fo TCA cycle
isocitrate dehydrogenase
rate limiting step of glycogenesis
glycogen synthase
rate limiting step of de novo pyramidine synthesis
carbomyl phosphate syntahse II
rate limiting step of de novo purine synthesis
glutamade phosphoribosylpyrophosphate (PRPP) amidotransferase
what enzymes are vitamin b7 (biotin) cofactors for
cabroxylation enzymes;
pyruvate carboxylase
acetyl CoA carboxylase
priopionyl carboxylase
what amino acid and co factor are used for the production of GABA and glutathione ?
glutamate and pyridoxine (B6)
what amino acid and co factors are required for the production of serotonin and melatonin
tryptophan and BH4, pyridoxine (B6)
what amino acid and co factors are required for the production of niacin?
what is niacin a precursor to?
trytophan, B6 (pryidoxine) and B2 (riboflavin)
niacin is a precursor to NAD and NADP
difference in von gierkes vs corris disease
von gierks –> glucose 6 phosphate deficiency
corri’s –> debranching enzymes alpha glucosidase
corri’s has milder symptoms and normal blood lactate level
oxidative decarboxylation of pyruvate requires what cofactor
vitamin B1
(pyruvate to acetyl CoA by pyruvate dehydrogenase complex)
describe how PTH increases Ca through increasing osteoclast activity
indirect stimulation of osteoclast activity through osteoblast-mediated release of cytokines
blotting procedures
southern blot = DNA
northern blot = RNA
western blot = protein
what substance is required to aid in absorption of non-haem iron in the gut
vitamin C
G1 phase
cells divide and replicate through the cell cycle
S phase
DNA replication
G2 phase
preparing for mitotis
the defective enzyme in maple syrup disease requires what co factor
alpha ketoacid dehydrogenase require thiamine pyrophosphate (B1)
amino acids involved in the first step in haem synthesis
glycine + succinyl-CoA = aminolevulinic acid
site of O-linked glycosylation
golgi apparatus
how does hypokalaemia cause metabolic alkalosis
low levels of K cause K to shift outside the cells. In compensation hydrogen ions enter the cells to maintain neutrality = alkalotic
