biochem 4 clinical correlations

Question 1

Glucose 6-Phosphate Dehydrogenase Deficiency MOA

Answer 1

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

Question 2

Why does Glucose 6-Phosphate Dehydrogenase Deficiency affect RBC

Answer 2

Affects RBC the most because they rely on the pentose phosphate pathway to provide sole means for NADPH production

Question 3

Glucose 6-Phosphate Dehydrogenase Deficiency causes what?

This is precipitated by?

5 THINGS

Answer 3

hemolytic anemia

exposed to oxidant drugs (abx, antimalarial, antipyretic), fava beans (Mediterranean diet), or contract infection

Question 4

Glucose 6-Phosphate Dehydrogenase Deficiency anesthesia care?

Answer 4

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

Question 5

Mucopolysaccharidoses (Hurler Syndrome)

Answer 5

: 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)

Question 6

Glycosaminoglycans are important for?

Answer 6

connective tissues

Question 7

Six major GAGs found in body?

Answer 7

 Chondroitin, keratan, dermatan, heparin, heparin sulfate, and hyaluronic acid  Chondroitin and keratan found in cartilage

Question 8

Glycoproteins are made up of?

Answer 8

Proteins w/ small oligosaccharides are attached

Question 9

Membrane bound glycoproteins do what? 5 things tell me about address labels

Answer 9

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

Question 10

hemoglobin a1c is a

Answer 10

glycoprotein

Question 11

Hypoxia affects the production of energy how? the long answer 5 3

Answer 11

↓ mitochondrial ETC ↓ ATP & adenine nucleotides ↑ Na cellular swelling ↑ plasma membrane permeability ↓ ATP & adenine nucleotides ↑ calcium mitochondrial permeability transition

Question 12

Glycogen storage diseases is? 3 “synthesis or degradation”

Answer 12

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

Question 13

Lactic acidosis from CV collapse affects what pathway?

Answer 13

from CV collapse, failure to provide O2 o Impaired oxidative phosphorylation – decreased ATP synthesis

Question 14

Thiamine (vit B1) is

Answer 14

– important cofactor in metabolism of sugars and amino acid

Question 15

Thiamine (vit B1) deficiency affects whom?

Answer 15

alcoholics and eating disorders

Question 16

Thiamine (vit B1) deficiency causes?

enzymes 3

T

P

A

what organs affected most? 3 Why?

Answer 16

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

Question 17

Iron deficiency anemia affects 2 things? Leads to________in patient, caused by?

Answer 17

affects Hb affects iron containing cytochromes in ETC (cytochrome c) -Fatigue is also partly d/t lack of electron transport for ATP production

Question 18

Cyanide/ carbon monoxide poisoning 2 things what can cause this? how long did it run?

Answer 18

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

Question 19

Shivering

What does it?

Leads to ?

two things

What med used to treat?

Answer 19

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)

Question 20

Hyperthyroidism increase two things?

Answer 20

↑ transcription of TCA enzymes

↑ ETC activity & heat production

Question 21

after glycolysis where does NADH stay?

Answer 21

in the cytosol

Question 22

insulin down regulates or upregulates glucokinase/hexokinase

Answer 22

upregulates

Question 23

glucagon down regulates or upregulates glucokinase/hexokinase

Answer 23

down regulates

Question 24

insulin down regulates or upregulates phosphofructokinase

Answer 24

upregulates

Question 25

insulin down regulates or upregulates pyruvate kinase

Answer 25

upregulates

Question 26

glucagon down regulates or upregulates phosphofructokinase

Answer 26

down regulates

Question 27

glucagon down regulates or upregulates pyruvate kinase

Answer 27

down regulates

Question 28

Effect of insulin on glucose uptake & metabolism?

TK

PAC

G4

not receptor pathway, macro view

3 steps leads to 3 things

Answer 28

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

Question 29

Glycogen synthesis is inhibited by ?

Answer 29

phosphorylation of enzymes

Question 30

Glycogen synthesis is inhibition (fasted state) describe the process which receptor? 4 steps

Answer 30

Glucagon & Epi bind to their receptors (Gs) ↑ cAMP activate PKA inactivate glycogen synthase

Question 31

Why give glucagon for beta blocker overdose?

Answer 31

o Glucagon is given for ß blocker overdose  glucagon receptors on the heart also stimulate Gs  ↑ chronotropy, dromotropy, and inotropy

Question 32

Hepatic gluconeogenesis(fasted) is vital for maintenance of blood sugar. Its increased by what 5 things? hormones/NT

Answer 32

 Glucocorticoids (cortisol)  Epinephrine  Glucagon  Growth hormone  Thyroid hormone

Question 33

Hepatic gluconeogenesis is inhibited by?

Answer 33

insulin

Question 34

Genetic pyruvate dehydrogenase deficiency

Answer 34

resulting in congenital lactic acidosis by shunting to lactate pathway

CNS defect and early death

similar to arsenic poisoning