biochem 4 clinical correlations Flashcards
Glucose 6-Phosphate Dehydrogenase Deficiency MOA
inability to form NADPH for maintenance of reduced glutathione – important antioxidant – increase in reactive species Hydrogen peroxide (H2O2) in the RBC, damage to erythrocyte wall, RBC dies early
Why does Glucose 6-Phosphate Dehydrogenase Deficiency affect RBC
Affects RBC the most because they rely on the pentose phosphate pathway to provide sole means for NADPH production
Glucose 6-Phosphate Dehydrogenase Deficiency causes what?
This is precipitated by?
5 THINGS
hemolytic anemia
exposed to oxidant drugs (abx, antimalarial, antipyretic), fava beans (Mediterranean diet), or contract infection
Glucose 6-Phosphate Dehydrogenase Deficiency anesthesia care?
management for pain and anxiety should include meds that are safe and have not been shown to cause oxidant stress or hemolytic crisis, such as benzos, propofol, fentanyl, and ketamine Rarely need to transfuse
Mucopolysaccharidoses (Hurler Syndrome)
: hereditary d/o characterized by accumulation of GAGs in various tissues Deficiency in enzymes responsible for degrading GAGs Skeletal & extracellular matrix deformities & mental retardation (Hurler Syndrome)
Glycosaminoglycans are important for?
connective tissues
Six major GAGs found in body?
Chondroitin, keratan, dermatan, heparin, heparin sulfate, and hyaluronic acid Chondroitin and keratan found in cartilage
Glycoproteins are made up of?
Proteins w/ small oligosaccharides are attached
Membrane bound glycoproteins do what? 5 things tell me about address labels
cell surface recognition, antigenicity components of extracellular matrix,globular proteins in plasma, mucins of GI/ GU tracts, Proteins have certain signal sequences (address labels) – determine direction & destination
hemoglobin a1c is a
glycoprotein
Hypoxia affects the production of energy how? the long answer 5 3
↓ mitochondrial ETC ↓ ATP & adenine nucleotides ↑ Na cellular swelling ↑ plasma membrane permeability ↓ ATP & adenine nucleotides ↑ calcium mitochondrial permeability transition
Glycogen storage diseases is? 3 “synthesis or degradation”
genetic diseases resulting in a defect in either enzymes of synthesis or degradation -Accumulation of abnormal amounts of carbohydrates or lipids primarily due to decreased degradation -abnormal structural glycogen
Lactic acidosis from CV collapse affects what pathway?
from CV collapse, failure to provide O2 o Impaired oxidative phosphorylation – decreased ATP synthesis
Thiamine (vit B1) is
– important cofactor in metabolism of sugars and amino acid
Thiamine (vit B1) deficiency affects whom?
alcoholics and eating disorders
Thiamine (vit B1) deficiency causes?
enzymes 3
T
P
A
what organs affected most? 3 Why?
Deficiency results in abnormal functioning of enzymes
Transketolase: pentose phosphate pathway
Pyruvate dehydrogenase: glycolysis; pyruvate acetyl CoA
α-ketoglutarate dehydrogenase:TCA cycle; α-ketoglutarate succinyl-CoA
heart, skeletal muscle, nervous tissue
because they rely on high rates of ATP production
Iron deficiency anemia affects 2 things? Leads to________in patient, caused by?
affects Hb affects iron containing cytochromes in ETC (cytochrome c) -Fatigue is also partly d/t lack of electron transport for ATP production
Cyanide/ carbon monoxide poisoning 2 things what can cause this? how long did it run?
bind to iron in cytochrome C & prevents electron transport Mitochondrial respiration & energy production cease – cell death
Nitroprusside: used to rapidly ↓ BP; can result in conversion to cyanide & poison ETC (cytochrome C)
In prolonged infusions of 24-48 hrs
Shivering
What does it?
Leads to ?
two things
What med used to treat?
muscular contraction
Increased ATP hydrolysis and synthesis
creates heat O2 consumption increased d/t stimulated ETC
energy lost heat
Demerol – used to stop shivering in cardiac patients (need to decrease O2 consumption) – atropine-like effects (↑ HR)
Hyperthyroidism increase two things?
↑ transcription of TCA enzymes
↑ ETC activity & heat production
after glycolysis where does NADH stay?
in the cytosol
insulin down regulates or upregulates glucokinase/hexokinase
upregulates
glucagon down regulates or upregulates glucokinase/hexokinase
down regulates
insulin down regulates or upregulates phosphofructokinase
upregulates
insulin down regulates or upregulates pyruvate kinase
upregulates
glucagon down regulates or upregulates phosphofructokinase
down regulates
glucagon down regulates or upregulates pyruvate kinase
down regulates
Effect of insulin on glucose uptake & metabolism?
TK
PAC
G4
not receptor pathway, macro view
3 steps leads to 3 things
Insulin binds to receptor (tyrosine kinase)
starts protein activation cascade
Translocation of GLUT 4 transporter to the membrane and influx of glucose
Glycogen synthesis
Glycolysis
Fatty acid/ triglyceride synthesis
Glycogen synthesis is inhibited by ?
phosphorylation of enzymes
Glycogen synthesis is inhibition (fasted state) describe the process which receptor? 4 steps
Glucagon & Epi bind to their receptors (Gs) ↑ cAMP activate PKA inactivate glycogen synthase
Why give glucagon for beta blocker overdose?
o Glucagon is given for ß blocker overdose glucagon receptors on the heart also stimulate Gs ↑ chronotropy, dromotropy, and inotropy
Hepatic gluconeogenesis(fasted) is vital for maintenance of blood sugar. Its increased by what 5 things? hormones/NT
Glucocorticoids (cortisol) Epinephrine Glucagon Growth hormone Thyroid hormone
Hepatic gluconeogenesis is inhibited by?
insulin
Genetic pyruvate dehydrogenase deficiency
resulting in congenital lactic acidosis by shunting to lactate pathway
CNS defect and early death
similar to arsenic poisoning
