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Flashcards in metabolism Deck (156):
1

mitochondria

beta oxidation
acetyl CoA production
TCA cycle
ox phos
ketogenesis

2

cytoplasm

glycolysis
fatty acid synthesis
HMP shunt
protein synthesis (RER)
steroid synthesis (SER)
cholesterol synthesis

3

both mito and cyto

heme synthesis
urea cycle
gluconeogenesis

4

kinase

uses ATP to add phosphate

5

phosphorylase

adds inorganic phosphate onto substrate w/o ATP

6

phosphatase

removes phosphate

7

dehydrogenase

catalyzes oxidation-reductions rxn

8

hyrdoxylase

adds hydroxyl (-OH)

9

Carboxylase

transfers CO2 w/help of biotin

10

mutase

relocates fnx grp w/in molecule

11

glycolysis rate-limiting step enzyme

phosphofructokinase

12

gluconeogenesis rate-limiting step enzyme

fructose 1,6 bisphosphatase

13

TCA cycle rate-limiting step enzyme

isocitrate dehydrogenase

14

glycogenesis rate-limiting step enzyme

glycogen synthase

15

glycogenolysis rate-limiting step enzyme

glycogen phosphorylase

16

HMP shunt rate-limiting step enzyme

carbamoyl phosphatate synthetase

17

De novo pyrimidine synthesis rate-limiting step enzyme

carbamoyl phosphate synthetase II

18

de novo purine synthesis rate-limiting step enzyme

glutamine-PRPP amidotransferase

19

ureas cycle rate-limiting step enzyme

carbamoyl phosphate synthetase I

20

FA synthesis rate-limiting step enzyme

acetyl-CoA carboxylase (ACC)

21

FA oxidation rate-limiting step enzyme

carnitine acyltransferase I

22

ketogenesis

HMG-CoA synthase

23

Cholesterol synthesis

HMG-CoA reductase

24

arsenic

glycolysis -> zero net ATP
inhibits lipoic acid
vomiting
rice-water stool
garlic breath

25

NAD

electron acceptor
usually catabolic processes

26

NADPH

electron acceptor
used in anabolic processes

27

hexokinase

phosphorylation of glucose - G6P
1st step of glycolysis and glycogen synthesis
expressed in most tissues except liver and beta cells
higher affinity/lower Km then glucokinase
lower capacity/Vmax then glucokinase
not induced by insulin
inhibited by G6P
gene mutation NOT associated w/ MODY

28

glucokinase

phosphorylation of glucose - G6P
1st step of glycolysis and glycogen synthesis
expressed in liver and beta cells
lower affinity/higher Km then hexokinase
higher capacity/Vmax then hexokinase
IS induced by insulin
NOT inhibited by G6P
gene mutation IS associated w/ MODY

29

which glycolysis enzymes require ATP?

hexokinase/glucokinase
phosphofructokinase-1 (RLS)

30

which glycolysis enzymes produce ATP?

phosphoglycerate kinase
pyruvate kinase

31

fructose 2.6 bisphosphonate

FBPase-2 and PFK-2 are same enzyme whose direction is reversed by phosphorylation via PKA
fasting: increased glucagon -> increased cAMP -> increased PKA -> increased FBPase 2 -> less glycolysis or gluconeogenesis
fed: increased insulin -> decreased cAMP -> decreased PKA -> increased PFK-2 -> more glycolysis and less gluconeogenesis

32

pyruvate dehydrogenase complex

mito enzyme complex linking glycolysis and TCA cycle (active in fed state)
pyruvate + NAD + CoA -> acetyl CoA + CO2 + NADH
activated by exercise which increases NAD, ADP, and Ca

33

pyruvate dehydrogenase complex deficiency

x-linked
build-up of pyruvate -> lactate and alanine
neuro defects, lactic acidosis, increased serum alanine starting in infancy

34

Tx of pyruvate dehydrogenase complex deficiency

increase intake of ketogenic nutrients
high fat
lysine and leucine

35

pyruvate can become what?

alanine (via ALT for Cahill cycle)
oxaloacetate (via PC for TCA cycle or gluconeogenesis)
acetyl-CoA (via PDH for TCA cycle)
Lactate ( via LDH for Cori Cycle)

36

TCA cycle

Citrate Is Krebs Starting Substrate For Making Oxaloacetate
citrate
isocitrate
alpha-KG
succinyl CoA
succinate
fumarate
malate
oxaloacetate

37

rotenone

blocks complex I of ETC

38

antimycin A

blocks complex III of ETC

39

cyanide

blocks complex IV of ETC

40

CO

blocks complex IV of ETC

41

Oligomycin

blocks complex V(ATP synthase) of ETC

42

uncoupling agents

2,4 dinitrophenol
aspirin
thermogenin in brown fat

43

gluconeogenesis irreversible enzymes

Pathway Produces Fresh Glucose
pyruvate carboxylase
phosphoenolpyruvate carboxykinase
fructose 1,6 bisphosphatase
glucose 6 phosphate

44

pyruvate carboxylase

in mito
pyruvate -> oxaloacetate

45

phosphoenolpyruvate carboxykinase

in cytosol
oxaloacetate -> phophoenolpyruvate

46

fructose 1,6 bisphosphatase

in cytosol
fructose 1,6 bisphosphate -> fructose 6 phosphate

47

glucose 6 phosphatase

in ER
G6P -> glucose

48

HMP shunt/pentose phosphate pathway

provides source of NADPH from G6P
yields ribose for nucleotide synthesis
NO ATP used or produces
occurs in lactating mammary glands, liver, adrenal Cx

49

oxidative rxn

use NADP+
create and inhibited by NADPH
produce CO2
irreversible

50

nonoxidative rxns

reversible

51

G6PD deficiency

XR
MC human enzyme deficiency
more prevalent in blacks
increases malarial resistance
G6PD required to replenish NADPH which is needed for glutathione reductase

52

G6PD presenation

hemolytic anemia following favao beans, sulfonamides, primaquine, atnituberculosis drugs, or infection

53

G6PD PBS

heinz bodies- denatured hemoglobin precipitates in RBCs
bite cells- results from phagocytic removal of Heinz bodies
'Bite into some Heinz ketchup on fava beans'

54

essential fructosuria

defect in fructokinase- AR
benign asymptomatic condition since fructose not tapped in cells
fructose in blood and urine

55

fructose intolerance

AR
deficiency of aldolase B
fructose-1-phosphate accumulates -> decreased bioavailability of phosphate -> inhibition of glycogenolysis and gluconeogenesis
urine dip stick neg

56

symptoms of fructose intolerance

hypoglycemia, jaundice, cirrhosis, vomiting

57

Tx of fructose intolerance

decrease fructose and sucrose in diet

58

galactokinase deficiency

galactitol accumulates if galactose in diet
mild
AR

59

symptoms of glactokinase deficiency

galactose in blood and urine
infantile cataracts
failure to track objects or develop a social smile

60

classic galactosemia

absence of galactose-1-phosphate uridyltransferase
AR
accumulation of toxic substances in lens of eye

61

symptoms of classic galatosemia

failure to thrive
jaundice
hepatomegaly
infantile cataracts
intellectual disability
E. coli sepsis

62

Tx of classic galactosemia

exclude galactose and lactose from diet

63

sorbitol

glucose can be converted to sorbitol vis aldose reductase
can then be converted to fructose via sorbitol dehydrogenase

64

sorbitol dehydrogenase deficiency

intracellular sorbitol accumulation -> osmotic damage (cataracts, retinopathy, peripheral neuropathy)
seen in DM

65

primary lactase deficiency

age dependent decline after childhood
common in asian, african, or native american descent

66

secondary lactase deficiency

loss of BBE d/t gastroenteritis, autoimmune disease, etc...

67

congenital lactase deficiency

rare
defective gene

68

lactase deficiency

lactase usually breaks lactose into glucose and galactose
stool decreased pH
breath shows increased hydrogen

69

symptoms of lactase deficiency

bloating, cramps, flatulence, osmotic diarrhea

70

glucogenic essential AAs

methionine (Met)
Valine (Val)
Histadine (His)

71

gluconeogenic/ketogenic essential AAs

isoleucine (Ile)
pheylalanine (Phe)
threonine (Thr)
tryptophan (Trp)

72

ketogenic essential AAs

leusine (Leu)
lysine (Lys)

73

acidic AAs

aspartic acid (Asp)
Glutamic acid (Glu)

74

basic AAs

arginine (Arg)
lysine (Lys)
histadine (His)
Arg and Lys in histones
Arg and His needed during growth

75

urea cycle

excess nitrogen converted to urea
Ordinarily Careless Crappers Are Also Frivolous About Urination
Ornithine + Carbamoyl phosphate -> Citrulline
Citrulline + Aspartate -> Arginosuccinate -> Fumarate +Arginine
Arginine -> Urea +Ornithine

76

hyperammonemia

excess NH4 -> depletes alpha ketoglurarate -> inhibits TCA cycle
tremor, slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision

77

Tx of hyperammonemia

limit protein in diet
lactulose -> acidifies GI tract to trap NH4
Rifaximin -> decrease colonic ammoniagenic bacteria
benzoate or phelbutyrate -> bind AAs

78

N-acetylglutamate synthase deficiency

required cofactor for carbamoyl phosphate snthetase I -> hyperammonemia
presents in neonates as poorly regulated resp and body temp, poor feeding, developmental delay, intellectual disability

79

ornithine transcarbamylase deficiency

MC urea cycle disorder
XR (other urea cycle disorders AR)
usually presents first few days of life, but may be later
excess carbamoyl phosphate is converted to orotic acid

80

findings in ornithine transcarbamylase deficiency

increased orotic acid in blood and urine
decreased BUN
symptoms of hyperammonemia
NO megaloblastic anemia in contrast to orotic aciduria

81

pheylketonruia

AR
d/t decreased phenylalanine hydroxylase or decreased tetrahydrobiopterin cofactor (malignant PKU)
increased phenylalanine -> pheylketones in urine

82

findings of PKU

normal at birth b/c of maternal enzyme
intellectual disability
growth retardation
seizures
fair skin
eczema
musty body odor

83

Tx of PKU

decreased phenylalanine and increased tyrosine in diet
tetrahydrobiopterin supplementation
cannot eat aspartame

84

PKU memory jog

disorder of aromatic aa meta -> musty body odor

85

maternal PKU

lack of proper dietary therapy during prego
findings in infant -> microcephaly, intellectual disability, growth retardation, congenital heart defects

86

maple syrup urine disease

AR
blocked degresation of brr aa (isoleucine, leucine, and valine) d/t decreased alpha ketoacid dehydrogenase

87

symptoms of maple syrup urine disease

severe CNS defects
intellectual disability
death
urine smells like maple syrup/burnt sugar

88

Tx of maple syrup urine disease

restriction of isoleucine, leucine, and valine in diet
thiamine supplementation

89

maple syrup urine disease pneumonic

I Love Vermont maple syrup from maple trees w/Brr

90

Alkaptnuria/ochronosis

AR, usually benign
deficiency of homogentisate oxidase in degradative pathway of tyrosine to fumarate-> pigment forming homogentisic acid accumulates in tissues

91

alkaptnuria/ochronosis findings

dark CT
brown pigmented sclera
urine turns black on prolonged exposure to air
may have debilitating arthralgias

92

homocystinuria

all types AR
excess homocysteine in urine
intellectual disability
osteoporosis
marfanoid habitus
kyphosis
lens subluxation
thrombosis and atherosclerosis

93

cystinuria

AR, common
defect of renal PCT and intestinal aa transport
prevents reabsorption of COLA
hexagonal cystine stones
urinary cyanide-nitroprusside test Dx

94

COLA

cysteine
ornithine
lysine
arginine

95

cystinuria Tx

chelating (pencicillamine)
hydration

96

glycogen storage diseases

all AR
Very Poor Carb Meta
Von Gierke's disease (type I)
Pompe (type II)
Cori (type III)
McArdle (type V)

97

Von Gierke's what enzyme?

G6P
AR

98

Von Gierke's findings

severe fasting hypoglycemia
big increase in glycogen in liver
increased blood lactate
increased TGs
increased uric acid
hepatomegaly

99

Von Gierke's Tx

frequent oral glucose/cornstarch
avoid fructose and galactose

100

Pompe what enzyme?

lysosomal alpha 1,4 glucosidase (acid maltase)
AR

101

Pompe findings

cardiomegaly/hypertrophic cardiomyopathy
exercise intolerance
systemic findings -> early death

102

Pompe acronym

Pompe trashes the Pumps (heart, mm, liver)

103

cori disease what enzyme?

debrr/alpha-1,6 glucosidase

104

cori disease findings

milder form of type I w/normal blood lactate levels, gluconeogenesis intact
type I:
severe fasting hypoglycemia
big increase in glycogen in liver
increased blood lactate
increased TGs
increased uric acid
hepatomegaly

105

McArdles disease

increase glycogen in mm
but mm cannot break it down -> painful mm cramps
myoglobinuria w/strenuous exercise
arrhythmia from electrolyte abnormalities
blood glucose typically normal

106

McArdles enzyme

skeletal mmm glycogen phosporylase/myophosphorylase

107

McArdles Tx

vit B6 (pyridoxine)

108

Fabry disease

XR
deficient alpha galactosidase
accumulates ceramide trihexoside

109

fabry findings

peripheral neuropathy hands/feet
angiokeratomas
cardiovascular/renal disease

110

gaucher disease

AR
deficient glucocerebrosidase
accumulates glucocerebroside
most common lysosomal storage disease

111

gaucher findings

hepatosplenomegaly
pancyotpenia
osteoporosis
aseptic necrosis of femur
bone crises
gaucher cells (lipid laden macros resembling crumpled tissue paper)

112

gaucher Tx

recombinant glucocerebrosidase

113

Niemann pick disease

AR
deficient spingomyelinase
accumulates spingomyelin

114

niemann pick findings

progressive neurodegeneration
hepatosplenomegaly
foam cells
cherry red spot on macula

115

tay-sachs disease

AR
deficient hexosamindase A
accumates GM2 ganglioside

116

tay sachs findings

progressive neurodegeneration
developmental delay
cherry red spot on macula
lysosomes w/onion skin
NO hepatosplenomegaly

117

krabbe disease

AR
deficient galactocerebrosidase
accumulates galactocerebroside and psychosine

118

krabbe disease findings

peripheral neuropathy
developmental delay
optic atrophy
globoid cells

119

metachromatic leukodystrophy

AR
deficient in arylsulfatase A
accumulates cerebroside sulfate

120

metachromatic leukodystrophy

central and peripheral demyelination w/ataxia and dementia

121

hurler syndrome

AR
deficient alpha-L-iduronidase
accumulates heparan sulfate

122

hurler syndrome findings

developmental delay
gargoylism
airway obstruction
corenal clouding
hepatosplenomegaly

123

hunter syndrome

XR
deficient iduronate sulfatase
accumulates heparan sulfate and dermatan sulfate

124

hunter syndrome findings

mild hurler + aggression
no corneal clouding

125

Niemann picks acronym

No man picks his nose w/his sphinger (sphingomyelinase)

126

Tay-sachs acronym

Tay-SaX lacks heXosaminidase

127

Hunters syndrome acronym

Hunters see clearly (no corneal clouding) and aggressively aim for the X (XR)

128

which lysosomal diseases assocaites w/Ashkenazi Jews

Tay-Sachs
Niemann picks
gaucher

129

systemic primary carnitine deficiency

defect in transport of LCFA into mito
toxic accumulation
weakness, hyptonia, and hypoketotic hypoglycemia

130

medium chain acryl-CoA dehydrogenase deficiency

AR
cannot break down FAs into Acetyl CoA
accumulation of 8-10 carbon fatty acyl carnitines in blood
hypoketotic hypoglycemia

131

medium chain acryl-CoA dehydrogenase deficiency presentation

infancy- early childhoos
vomiting, lethargy, seizures, coma, liver dysfunction
may cause sudden death, must avoid fasting

132

1g protein or fat

4kcal

133

1g fat

9kcal

134

1g alcohol

7kcal

135

cholesterol synthesis RLE

HMG-CoA reductase (induced by insulin) converts HMG-CoA -> mevalonate

136

LPL

lipoprotein lipase
degradation of TGs circulating in chylomicrons and VLDLs
on vascular endo surface

137

HL

hepatic lipase
degradation of TGs remaining in IDL

138

Hormone-sensitive lipase

degradation of TGs stored in adipocytes

139

LCAT

catalyzes esterification of cholesterol

140

apolipoprotein E

mediates remnant uptake
found on chylomicron, chylomicron remnant, VLDL, IDL, HDL

141

apoplipoprotein A-I

activates LCAT
found on chylomicron and HDL

142

apoplipoprotein C-II

lipoprotein lipase cofactors
found on chylomicron, VLDL, HDL

143

apoplipoprotein B-48

mediates chylomicron secretion
found on chylomicron, chylomicron remanant

144

apoplipoprotein B-100

binds LDL R
found on VLDL, IDL, LDL

145

LDL

transports cholesterol from liver to tissues

146

HDL

transports cholesterol from periphery to liver
acts as repository for apoplipoprotein C and E (needed for chylomicron and VLDL meta) secreted both from liver and intestines
alcohol increases synthesis

147

chylomicron

delivers dietary TGs to periphery
delivers cholester to liver in form of chylomicron remnant
secreted by intestinal epi

148

VLDL

delivers hepatic TGs to periphery
secreted by liver

149

IDL

formed in degradation of VLDL
delivers TGs and cholesterol to liver

150

LDL

delivers hepatic cholesterol to peripheral tissues
formed by hepatic lipase modification of IDL in periphery
taken up by target cells via R mediated endocytosis

151

familial dysplipidemia type I

hyper-chylomicronemia
increased chylomicrons, TGs, and cholesterol in blood
creamy layer in supernatant
AR

152

path of familial dysplipidemia type I

lipoprotein lipase deficiency or altered apolipoprotein C-II
causes pancreatitis, hepatosplenomegaly, eruptive/pruitic xanthoms
no increased risk for atherosclerosis

153

familial dyslipidemia type IIa

familial hypercholesterolemia
increased LDL, cholesterol
AD

154

path of familial dyslipidemia type IIa

absent or defective LDL R
heterozyogotes have cholesterol 300+
homozygotes have cholesterol 700+ (rare)
accelerated atheroscloersis (MI

155

familial dyslipidemia type IV

familial hypertriglyceridemia
increased VLDL, TG
AD

156

path of familial dyslipidemia type IV

hepatic overproduction of VLDL
TGs >1000 can cause acute pancreatitis