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Step I > metabolism > Flashcards

metabolism Flashcards

1
Q

mitochondria

A 
beta oxidation
acetyl CoA production
TCA cycle
ox phos
ketogenesis
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2
Q

cytoplasm

A 
glycolysis
fatty acid synthesis
HMP shunt
protein synthesis (RER)
steroid synthesis (SER)
cholesterol synthesis
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3
Q

both mito and cyto

A

heme synthesis
urea cycle
gluconeogenesis

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4
Q

kinase

A

uses ATP to add phosphate

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5
Q

phosphorylase

A

adds inorganic phosphate onto substrate w/o ATP

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6
Q

phosphatase

A

removes phosphate

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7
Q

dehydrogenase

A

catalyzes oxidation-reductions rxn

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8
Q

hyrdoxylase

A

adds hydroxyl (-OH)

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9
Q

Carboxylase

A

transfers CO2 w/help of biotin

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10
Q

mutase

A

relocates fnx grp w/in molecule

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11
Q

glycolysis rate-limiting step enzyme

A

phosphofructokinase

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12
Q

gluconeogenesis rate-limiting step enzyme

A

fructose 1,6 bisphosphatase

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13
Q

TCA cycle rate-limiting step enzyme

A

isocitrate dehydrogenase

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14
Q

glycogenesis rate-limiting step enzyme

A

glycogen synthase

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15
Q

glycogenolysis rate-limiting step enzyme

A

glycogen phosphorylase

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16
Q

HMP shunt rate-limiting step enzyme

A

carbamoyl phosphatate synthetase

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17
Q

De novo pyrimidine synthesis rate-limiting step enzyme

A

carbamoyl phosphate synthetase II

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18
Q

de novo purine synthesis rate-limiting step enzyme

A

glutamine-PRPP amidotransferase

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19
Q

ureas cycle rate-limiting step enzyme

A

carbamoyl phosphate synthetase I

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20
Q

FA synthesis rate-limiting step enzyme

A

acetyl-CoA carboxylase (ACC)

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21
Q

FA oxidation rate-limiting step enzyme

A

carnitine acyltransferase I

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22
Q

ketogenesis

A

HMG-CoA synthase

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23
Q

Cholesterol synthesis

A

HMG-CoA reductase

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24
Q

arsenic

A 
glycolysis -> zero net ATP
inhibits lipoic acid
vomiting
rice-water stool
garlic breath
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25
Q

NAD

A

electron acceptor

usually catabolic processes

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26
Q

NADPH

A

electron acceptor

used in anabolic processes

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27
Q

hexokinase

A

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

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28
Q

glucokinase

A 
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
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29
Q

which glycolysis enzymes require ATP?

A

hexokinase/glucokinase

phosphofructokinase-1 (RLS)

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30
Q

which glycolysis enzymes produce ATP?

A

phosphoglycerate kinase

pyruvate kinase

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31
Q

fructose 2.6 bisphosphonate

A

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

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32
Q

pyruvate dehydrogenase complex

A

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

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33
Q

pyruvate dehydrogenase complex deficiency

A

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

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34
Q

Tx of pyruvate dehydrogenase complex deficiency

A

increase intake of ketogenic nutrients
high fat
lysine and leucine

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35
Q

pyruvate can become what?

A

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)

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36
Q

TCA cycle

A 
Citrate Is Krebs Starting Substrate For Making Oxaloacetate
citrate
isocitrate
alpha-KG
succinyl CoA
succinate
fumarate
malate
oxaloacetate
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37
Q

rotenone

A

blocks complex I of ETC

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38
Q

antimycin A

A

blocks complex III of ETC

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39
Q

cyanide

A

blocks complex IV of ETC

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40
Q

CO

A

blocks complex IV of ETC

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41
Q

Oligomycin

A

blocks complex V(ATP synthase) of ETC

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42
Q

uncoupling agents

A

2,4 dinitrophenol
aspirin
thermogenin in brown fat

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43
Q

gluconeogenesis irreversible enzymes

A 
Pathway Produces Fresh Glucose
pyruvate carboxylase
phosphoenolpyruvate carboxykinase
fructose 1,6 bisphosphatase
glucose 6 phosphate
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44
Q

pyruvate carboxylase

A

in mito

pyruvate -> oxaloacetate

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45
Q

phosphoenolpyruvate carboxykinase

A

in cytosol

oxaloacetate -> phophoenolpyruvate

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46
Q

fructose 1,6 bisphosphatase

A

in cytosol

fructose 1,6 bisphosphate -> fructose 6 phosphate

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47
Q

glucose 6 phosphatase

A

in ER

G6P -> glucose

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48
Q

HMP shunt/pentose phosphate pathway

A

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

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49
Q

oxidative rxn

A

use NADP+
create and inhibited by NADPH
produce CO2
irreversible

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50
Q

nonoxidative rxns

A

reversible

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51
Q

G6PD deficiency

A 
XR
MC human enzyme deficiency 
more prevalent in blacks
increases malarial resistance
G6PD required to replenish NADPH which is needed for glutathione reductase
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52
Q

G6PD presenation

A

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

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53
Q

G6PD PBS

A

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

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54
Q

essential fructosuria

A

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

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55
Q

fructose intolerance

A

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

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56
Q

symptoms of fructose intolerance

A

hypoglycemia, jaundice, cirrhosis, vomiting

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57
Q

Tx of fructose intolerance

A

decrease fructose and sucrose in diet

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58
Q

galactokinase deficiency

A

galactitol accumulates if galactose in diet
mild
AR

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59
Q

symptoms of glactokinase deficiency

A

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

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60
Q

classic galactosemia

A

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

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61
Q

symptoms of classic galatosemia

A 
failure to thrive 
jaundice
hepatomegaly 
infantile cataracts
intellectual disability 
E. coli sepsis
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62
Q

Tx of classic galactosemia

A

exclude galactose and lactose from diet

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63
Q

sorbitol

A

glucose can be converted to sorbitol vis aldose reductase

can then be converted to fructose via sorbitol dehydrogenase

64
Q

sorbitol dehydrogenase deficiency

A

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

65
Q

primary lactase deficiency

A

age dependent decline after childhood

common in asian, african, or native american descent

66
Q

secondary lactase deficiency

A

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

67
Q

congenital lactase deficiency

A

rare

defective gene

68
Q

lactase deficiency

A

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

69
Q

symptoms of lactase deficiency

A

bloating, cramps, flatulence, osmotic diarrhea

70
Q

glucogenic essential AAs

A

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

71
Q

gluconeogenic/ketogenic essential AAs

A

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

72
Q

ketogenic essential AAs

A

leusine (Leu)

lysine (Lys)

73
Q

acidic AAs

A 
aspartic acid (Asp)
Glutamic acid (Glu)
74
Q

basic AAs

A 
arginine (Arg)
lysine (Lys)
histadine (His)
Arg and Lys in histones 
Arg and His  needed during growth
75
Q

urea cycle

A

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
Q

hyperammonemia

A

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

77
Q

Tx of hyperammonemia

A

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

78
Q

N-acetylglutamate synthase deficiency

A

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
Q

ornithine transcarbamylase deficiency

A

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
Q

findings in ornithine transcarbamylase deficiency

A

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

81
Q

pheylketonruia

A

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

82
Q

findings of PKU

A 
normal at birth b/c of maternal enzyme 
intellectual disability 
growth retardation
seizures
fair skin 
eczema
musty body odor
83
Q

Tx of PKU

A

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

84
Q

PKU memory jog

A

disorder of aromatic aa meta -> musty body odor

85
Q

maternal PKU

A

lack of proper dietary therapy during prego

findings in infant -> microcephaly, intellectual disability, growth retardation, congenital heart defects

86
Q

maple syrup urine disease

A

AR

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

87
Q

symptoms of maple syrup urine disease

A

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

88
Q

Tx of maple syrup urine disease

A

restriction of isoleucine, leucine, and valine in diet

thiamine supplementation

89
Q

maple syrup urine disease pneumonic

A

I Love Vermont maple syrup from maple trees w/Brr

90
Q

Alkaptnuria/ochronosis

A

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

91
Q

alkaptnuria/ochronosis findings

A

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

92
Q

homocystinuria

A 
all types AR
excess homocysteine in urine 
intellectual disability 
osteoporosis 
marfanoid habitus
kyphosis
lens subluxation
thrombosis and atherosclerosis
93
Q

cystinuria

A 
AR, common
defect of renal PCT and intestinal aa transport
prevents reabsorption of COLA
hexagonal cystine stones
urinary cyanide-nitroprusside test Dx
94
Q

COLA

A

cysteine
ornithine
lysine
arginine

95
Q

cystinuria Tx

A

chelating (pencicillamine)

hydration

96
Q

glycogen storage diseases

A 
all AR
Very Poor Carb Meta
Von Gierke's disease (type I)
Pompe (type II)
Cori (type III)
McArdle (type V)
97
Q

Von Gierke’s what enzyme?

A

G6P

AR

98
Q

Von Gierke’s findings

A 
severe fasting hypoglycemia
big increase in glycogen in liver
increased blood lactate
increased TGs
increased uric acid
hepatomegaly
99
Q

Von Gierke’s Tx

A

frequent oral glucose/cornstarch

avoid fructose and galactose

100
Q

Pompe what enzyme?

A

lysosomal alpha 1,4 glucosidase (acid maltase)

AR

101
Q

Pompe findings

A

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

102
Q

Pompe acronym

A

Pompe trashes the Pumps (heart, mm, liver)

103
Q

cori disease what enzyme?

A

debrr/alpha-1,6 glucosidase

104
Q

cori disease findings

A 
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
Q

McArdles disease

A

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
Q

McArdles enzyme

A

skeletal mmm glycogen phosporylase/myophosphorylase

107
Q

McArdles Tx

A

vit B6 (pyridoxine)

108
Q

Fabry disease

A

XR
deficient alpha galactosidase
accumulates ceramide trihexoside

109
Q

fabry findings

A

peripheral neuropathy hands/feet
angiokeratomas
cardiovascular/renal disease

110
Q

gaucher disease

A

AR
deficient glucocerebrosidase
accumulates glucocerebroside
most common lysosomal storage disease

111
Q

gaucher findings

A 
hepatosplenomegaly 
pancyotpenia
osteoporosis
aseptic necrosis of femur
bone crises
gaucher cells (lipid laden macros resembling crumpled tissue paper)
112
Q

gaucher Tx

A

recombinant glucocerebrosidase

113
Q

Niemann pick disease

A

AR
deficient spingomyelinase
accumulates spingomyelin

114
Q

niemann pick findings

A

progressive neurodegeneration
hepatosplenomegaly
foam cells
cherry red spot on macula

115
Q

tay-sachs disease

A

AR
deficient hexosamindase A
accumates GM2 ganglioside

116
Q

tay sachs findings

A 
progressive neurodegeneration
developmental delay 
cherry red spot on macula
lysosomes w/onion skin
NO hepatosplenomegaly
117
Q

krabbe disease

A

AR
deficient galactocerebrosidase
accumulates galactocerebroside and psychosine

118
Q

krabbe disease findings

A

peripheral neuropathy
developmental delay
optic atrophy
globoid cells

119
Q

metachromatic leukodystrophy

A

AR
deficient in arylsulfatase A
accumulates cerebroside sulfate

120
Q

metachromatic leukodystrophy

A

central and peripheral demyelination w/ataxia and dementia

121
Q

hurler syndrome

A

AR
deficient alpha-L-iduronidase
accumulates heparan sulfate

122
Q

hurler syndrome findings

A 
developmental delay
gargoylism
airway obstruction
corenal clouding
hepatosplenomegaly
123
Q

hunter syndrome

A

XR
deficient iduronate sulfatase
accumulates heparan sulfate and dermatan sulfate

124
Q

hunter syndrome findings

A

mild hurler + aggression

no corneal clouding

125
Q

Niemann picks acronym

A

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

126
Q

Tay-sachs acronym

A

Tay-SaX lacks heXosaminidase

127
Q

Hunters syndrome acronym

A

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

128
Q

which lysosomal diseases assocaites w/Ashkenazi Jews

A

Tay-Sachs
Niemann picks
gaucher

129
Q

systemic primary carnitine deficiency

A

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

130
Q

medium chain acryl-CoA dehydrogenase deficiency

A

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

131
Q

medium chain acryl-CoA dehydrogenase deficiency presentation

A

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

132
Q

1g protein or fat

A

4kcal

133
Q

1g fat

A

9kcal

134
Q

1g alcohol

A

7kcal

135
Q

cholesterol synthesis RLE

A

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

136
Q

LPL

A

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

137
Q

HL

A

hepatic lipase

degradation of TGs remaining in IDL

138
Q

Hormone-sensitive lipase

A

degradation of TGs stored in adipocytes

139
Q

LCAT

A

catalyzes esterification of cholesterol

140
Q

apolipoprotein E

A

mediates remnant uptake

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

141
Q

apoplipoprotein A-I

A

activates LCAT

found on chylomicron and HDL

142
Q

apoplipoprotein C-II

A

lipoprotein lipase cofactors

found on chylomicron, VLDL, HDL

143
Q

apoplipoprotein B-48

A

mediates chylomicron secretion

found on chylomicron, chylomicron remanant

144
Q

apoplipoprotein B-100

A

binds LDL R

found on VLDL, IDL, LDL

145
Q

LDL

A

transports cholesterol from liver to tissues

146
Q

HDL

A

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
Q

chylomicron

A

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

148
Q

VLDL

A

delivers hepatic TGs to periphery

secreted by liver

149
Q

IDL

A

formed in degradation of VLDL

delivers TGs and cholesterol to liver

150
Q

LDL

A

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
Q

familial dysplipidemia type I

A

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

152
Q

path of familial dysplipidemia type I

A

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

153
Q

familial dyslipidemia type IIa

A

familial hypercholesterolemia
increased LDL, cholesterol
AD

154
Q

path of familial dyslipidemia type IIa

A

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

155
Q

familial dyslipidemia type IV

A

familial hypertriglyceridemia
increased VLDL, TG
AD

156
Q

path of familial dyslipidemia type IV

A

hepatic overproduction of VLDL

TGs >1000 can cause acute pancreatitis

Step I (22 decks)

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