BIOCHEMISTRY Flashcards
RLE of glycolysis
step 3) phosphofructokinase-1
enzymes of irreversible steps of glycolysis ‘thermodynamic barriers’
step 1) glucokinase / hexokinase
step 3) phosphofructokinase-1
step 9) pyruvate kinase
irreversible steps of glycolysis
step 1) glucose –> glucose-6-phosphate
step 3) fructose-6-phosphate –> fructose-1-6-bisphosphate
step 9) Phosphoenolpyruvate –> pyruvate
glucose - G6P
F6P - F16BP
PEP - pyruate
what step does fluride inhibit in glycolysis
step 8) 2-PG –> PEP
removes Mg2+ & causes irreversible inhibition of enzyme enolase
what does Arsenate inhibit in glycolysis
stage 6) glyceraldehyde-3-P –> 1-3-bisphosphoglycerate
competes with PO4 for binding site on 1-3-BPG, no ATP produced
what step of glycolysis uses NADH
step 5) glyceraldehyde-3-phosphate –> 1-3-bisphosphoglycerate
uses: 2 NAD+ –> 2 NADH
what steps of glycolysis use (cost) ATP?
ATP –> ADP
step 1
step 3
whats steps of glycolysis produce ATP?
ADP –> ATP
step 6) 1-3-bisphosphoglycerate –> 3-phosphoglycerate
step 9) PEP –> pyruvate
what upregulates glycolysis?
insulin
ADP
AMP
Fructose-2-6-BP
Fructose-1-6-BP (at step 9)
what downregulates glycolysis
ATP
citrate
glucagon
alanine (at step 9)
acetyl-COA (at atep 9)
what gluconeogenesis enzymes differ from glycolysis?
(from top of glycolysis flowchart)
step 1) Glucose-6-phosphate
step 3) fructose-1-6-bisphosphate 1
how much energy produced from glycolysis
2 ATP
2 NADH
how much energy is produced from gluconeogenesis
4 ATP
2 GTP
2 NADH
gluconeogenesis can also occur from oxaloacetate in the TCA cycle via what enzyme?
oxaloacetate (TCA) –> PEP (Gluconeogenesis)
enzyme: PEP carboxykinase
in gluconeogenesis what co-factor does the enzyme require to convert pyruvate –> oxaloacetate
B7 (Biotin)
with pyruvate carboxylase
(occurs in mitochondria)
what stages of TCA cycle require (5) co-factors
B1, B2, 3B, B5, lipoic acid
step 1) pyruvate –> acetyl-CoA
enzyme: pyruvate dehydrogenase
step 6) a-ketoglutarate –> succinyl-CoA
enzyme: a-ketoglutarate dehydrogenase
what step of gluconeogenesis uses GDP as phosphate donor
oxaloacetate –> PEP
(step 2)
Pyruvate can be converted to ( ) or ( ) during intense exercise or starvation states & using which enzymes
cori cycle: lactate
lactate dehydrogense (LDH)
cahill cycle: alanine:
alanine transaminase (ALT)
how much energey is produced by TCA cycle
2 cycles:
3 NADH (= 2.5 ATP)
1 FADH2 (= 1.5 ATP)
1 GTP per acetyl-CoA (= 1ATP)
2 Co2
….. 20 ATP
what is the RLE of TCA cycle
isocitrate dehydrogenase
isocitrate –> a-ketoglutarate
step 4: (from pyruvate)
what enzymes of TCA cycle use NADH
step 4) isocitrate dehydrogenase
isocitrate –> a-ketoglutarate
step 5) a-ketoglutarate dehydrogenase
a-ketoglutarate –>succinyl-CoA
step 9) malate dehydrogenase
malate –> oxaloacetate
what step uses FADH2 in TCA cycle
step 7) succinate dehydrogenase
succinate –> fumerate
what enzyme of TC cycle odes arsenite inhibit
step 1) pyruvate dehydrogenase
pyruvate –> acetyl-CoA
what step of TCA uses GTP
step 6) succinate thiokinase
succinyl-CoA –> succinate
what are the regulatory enzymes in TCA cycle
step 2) citrate synthase
step 4) isocitrate dehydrogenase (RLE)
step 5) a-ketoglutarate dehydrogenase
newborn
metabolic acidosis
tachypnoea
hypoglycaemia
ketosis
hyperammonia
vomiting, dehydration, AMS
methylmalonic acidaemia
(or propionic acidaemia)
‘organic acidemia’
propionic acidaemia - would have low methylmalonic acid
accumulation of methylmalonate inhibits urea cycle –> hyperammonia
*
Urea cycle defects typically show no ketosis, while organic acidemias show ketosis + hyperammonemia, as in this case.*
sNRPs are ___ at the ___
single base substitutions at the splice acceptor site
transcription is the process where -? is made from -?
pre-mRNA
DNA
pre-RNA must undego post-transcriptional modification to create mature mRNA
i.e. removal of interons (by SnRPs)
pre-RNA must undego ___ to create mature mRNA
**post-transcriptional modification
i.e. removal of introns (by SnRPs)
mutation at** splice acceptor site** can result in
inclusion of interions
exclusion of exons
non-functional mRNA / protein
SRP (signal recognition particle) function
traffics
polypeptide-ribosome complex from the
cytosol to the RER
occurs after transcription
location of SRP (signal recognition particle)
cytosolic ribonucleoprotein
organic chemical compound is found in paint thinner
methanol
toxic metabolite of methanol metabolism
formic acid
anion gap metaboic acidosis
compensatory respiratory alkalosis
retinal oedema
putaminal haemorrhage
optic disc hyperaemia
GIT distress
neurologic depression
___-chain fatty acids don’t require carnitine shuttle
medium
**long chain fatty acids require ___ enzyme to shuttle them from cytoplasm into mitochondrial matrix
carnitine-acylcarnitine translocase
carnitine shuttle
enzyme dysfunction
LCFA nt shuttled
accumulate in liver/muscles
AR
childhood onset
encephalopathy, vomiting,
hypoketotic hypoglycemia
hyperammonemia
muscle weakness, skeletal myopathy cardiomyopathy, ventricular dysrhythmias
enzyme deficiency
carninte shuttle
carnitine-acylcarnitine translocase deficiency
can’t shuttle LCFA
symptoms of carnitine-acylcarnitine translocase deficiency triggered by
illness
fasting
Tx medium chain fatty acids
low fat, high carb formula
carnitine supplement
Lesch-Nyhan; defect in salvage of
guanine
hypoxanthine
defect in HGPRT
decreased levels guanine, hypoxanthine
increased levels xanthine, uric acid
folate has what affect on;
homocystine
methylmalonic acid
increased
normal
homocyteine –> methionine (folate & B12)
methylmalonyl-CoA - succinyl-coA (B12)
folate deficiency common in (4)
malnutrition
alcoholism
high cell turn over - leukaemia, sickle cell
anti-folate drugs
mutations in Kosak sequence impair
eukaryotes
translation of proteins
AUG methionine start codon
i.e. seen in B-thalassemia (point mutation affecting start codon)
what location is the cause of OTC deficiency
ornithine transcarbamylase (OTC) deficiency
C
male newborn
lethargy, poor feeding, vomiting 4
increased ammonia and orotic acid.
OTC deficiency
ornithine transcarbamylase (OTC) deficiency
what is increased in ornithine transcarbamylase (OTC) deficiency
orotic acid
(from accumulation carbamoyl phosphate)
decreased citrulline
hyperammonia
altered consciousness from DKA causing dehydration can alter consciousness via
glucose
osmotic diuresis
glucose in the urine draws water with it
hyperosmolar hyperglycemic state (HHS)
diabetic ketoacidosis (DKA)
Urea cycle defects typically show no ___ while organic acidemias show ___ + ___
ketosis
ketosis + hyperammonemia
generalized weakness
numbness and tingling UL/LL
difficulty walking
ataxic gait
decreased DTRs
haemolytic anaemia
vitamin deficiency
vitamin E
peripheral neuropathy
antioxidant
protects erythrocytes from free radicals
can be seen in **cystic fibrosis **-> problem absorbing fat-sol vitamins DEAK - pancreatic insufficiency
CF + vitamins -> think pancreas
peripheral neuropathy
dermatitis
sideroblastic anaemia
glossitis
seizures
vitamin B6 (pyridoxine)
seizures espeicially if isoniazid use setting
deficiency limits sythesis histamine, Hb and neurotransmiters
what enzyme does both liver and kidney possess to permit release of free glucose into the serum
glucose-6-phosphat_ase_
liveer - glucogenolysis & gluconeogenesis
kidney - gluconeogenesis
used during strenuous exercise
G-6-P hydrolyses glucose-6-phosphate to create free glucose molecules
endocytosis is affected by mutation in the ___ domain of LDL receptor
cytoplasmic
signalling for endocytosis occurs via cytoplasmic domain
extracellular domain mutation would affect LDL particles binding to LDL receptor
enzyme defects (2) causing homocystinuria
cystathionine b-synthase (↑ methionine)
methione synthase (↓ methionine)
look for difference in methionine concentration
homocysteine → cystathionine (requires vitamin B6)
homocysteine → methionine (requires vitamin B12)
