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46 Cards in this Set

  • Front
  • Back
irreversible enzymes in glycolysis (3)

function
hexokinase/glucokinase (glucose --> glucose-6-phosphate)

phosphofructokinase-1 [PFK-1] (fructose-6-phosphate -->
fructose 1,6-bisphosphate)*

pyruvate kinase (phosphoenolpyruvate [PEP] --> pyruvate)


* rate-limiting step in glycolysis
glucokinase is located in (2)
hepatocytes
β-islet cells

(gLucokinase)
glucokinase is induced by
insulin
glucokinase:

Km
capacity
high Km (low affinity)
high capacity
hexokinase is inhibited by
glucose-6-phosphate
hexokinase:

Km
capacity
low Km (high affinity)
low capacity
rate-limiting enzyme of glycolysis
PFK-1
PFK-1 is directly inhibited by (2)
ATP
citrate
PFK-1 is directly activated by
AMP
PFK-1 is indirectly stimulated by
insulin
(stimulation of PFK-2 results in fructose 2,6-bisphosphate synthesis)

*fructose 2,6-bisphosphate is the most potent activator of PFK-1*
(overrides inhibition of PFK-1 by ATP and citrate)
PFK-1 is indirectly inhibited by
glucagon
(inhibition of PFK-2 results in inhibition of fructose 2,6-bisphosphate synthesis)
2,3 BPG is synthesized during
glycolysis (from 1,3 BPG via mutase)
pyruvate kinase:

activated by

inhibited by (2)
fructose 1,6-bisphosphate

ATP
alanine
function of lactate dehydrogenase (LDH)
reduces pyruvate to lactate (NAD+ is regenerated)
consequence of reduction of pyruvate to lactate by LDH
oxidation of NADH to NAD+

(NAD+ is used in glycolysis by G3P dehydrogenase)
DHAP from glycolysis is used to synthesize
TG's
high-energy intermediates in glycolysis that are used to generate ATP (2)
1,3 BPG
PEP
pyruvate dehydrogenase is inhibited (3)
NADH
ATP
acetyl-CoA
glycolytic enzyme deficiencies result in (2)
hemolytic anemia (without heinz bodies; e.g., pyruvate kinase deficiency)

increased 2,3 BPG (O2 unloaded from Hb more readily)
most common glycolytic enzyme deficiency
pyruvate kinase
galactokinase deficiency results in

consequence
mild galactosemia

galactose is converted to galactitol by aldose reductase in the lens
trapping of galactitol in the lens causes (2)
swelling of lens

cataracts
enzyme deficiency:

catracts early in life
vomiting and diarrhea following lactose ingestion
lethargy
liver damage --> hyperbilirubinemia
mental retardation
galactose 1-P uridyltransferase deficiency

("severe galactosemia")
fructokinase deficiency results in
essential fructosuria-benign condition

(non-glucose sugar detected by urine dipstick test)
enzyme deficiency:

vomiting
lethargy
liver damage --> hyperbilirubinemia
hypoglycemia (↓ P --> ↓ glycogenolysis and ↓ gluconeogenesis)
hyperuricemia
renal proximal tubule defect (Fanconi)
aldolase B (fructose 1-P aldolase) deficiency

("fructose intolerance")
pyruvate dehydrogenase (PDH) complex cofactors
thiamine pyrophosphate (TPP) -thiamine (vit. B1)
FAD - riboflavin (vit. B2)
NAD+ - niacin (vit. B3)
CoA - pantothenate (vit. B5)
lipoic acid

(the first four water-soluble vitamins + lipoic acid)
PDH:

function

activated by (3)

inhibited by (3)
pyruvate --> acetyl-CoA

↑ NAD+/NADH ratio
ADP
Ca2+

NADH
ATP
acetyl-CoA
lipoic acid is inhibited by
arsenic
signs of arsenic poisoning (3)
vomiting
rice water stools
garlic breath
PDH deficiency is common in

reason
alcoholics

(thiamine deficiency-no TPP)
PDH deficiency results in
lactic acidosis

(pyruvate builds up and is converted to lactate by lactate dehydrogenase)
Tx for PDH deficiency
increase intake of ketogenic nutrients
ketogenic nutrients (3)
fats
lysine (purely ketogenic aa)
leucine (purely ketogenic aa)
pyruvate is converted to alanine by
ALT
anaerobic glycolysis is the major energy-producing pathway in (6)
RBC's
leukocytes
kidney medulla (very low O2)
cornea
lens
testes
rate-limiting enzyme of the TCA cycle

function
isocitrate dehydrogenase (IDH)

isocitrate-->alpha-ketoglutarate
isocitrate dehydrogenase:

activated by

inhibited by (2)
ADP

NADH
ATP
α-ketoglutarate dehydrogenase complex cofactors
thiaminepyrophosphate (TPP) - thiamine (vit. B1)
FAD - riboflavin (vit. B2)
NAD+ - niacin (vit. B3)
CoA - pantothenate (vit. B5)
lipoic acid

(the first four water-soluble vitamins + lipoic acid)
α-ketoglutarate dehydrogenase is inhibited by (3)
succinyl-CoA
NADH
ATP
only enzyme of the TCA cycle not found in the mitochondrial matrix

location
succinate dehydrogenase

inner mitochondrial membrane (complex II)
NADH dehydrogenase complex I blocked by (2)
barbiturates
rotenone
coenzyme Q (ubiquinone) blocked by
doxorubicin
cytochrome b/c1 (complex III) blocked by
antimycin A
cytochrome a/a3 (Cu2+), complex IV, and cytochrome oxidase blocked by (3)
cyanide
CO
azide
ATP synthase blocked by
oligomycin
uncoupling agents (4)

result in (3)
uncoupling protein (UCP)
thermogenin (brown adipose tissue)
2,4-DNP
aspirin

↓ ATP production
↑ O2 consumption
↑ oxidation of NADH