FA 2015 - Metabolism Flashcards
(90 cards)
1
Q
Rate Limiting of Glycolysis
A
phosphofructokinase - 1
2
Q
regulators of rate limiting of glycolysis
A
phosphofructokinase-1
+ AMP + fructose26bp
- ATP - citrate
3
Q
Rate limiting of gluconeogenesis
A
fructose 1,6 bisphosphatase
4
Q
regulators of rate limiting of gluconeogenesis
A
fructose 1,6 bisphosphatase
+ ATP + acetyl-CoA + citrate
- AMP - fructose 26bp
5
Q
rate limiting of the TCA
A
isocitrate dehydrogenase
6
Q
regulators of rate limiting of TCA
A
isocitrate dehydrogenase
+ ADP
- ATP - NADH
7
Q
rate limiting of glycogenesis
A
glycogen synthase
8
Q
regulators of rate limiting of glycogenesis
A
glycogen synthase
+ insulin + cortisol + glucose 6p
- epi - glucagon
9
Q
rate limiting of glycogenolysis
A
glycogen phosphorylase PLP
10
Q
regulators of rate limiting of glycogenolysis
A
glycogen phosphorylase PLP
+ epi + glucagon + AMP (also stimulates glycolysis)
- insulin - cortisol - glucose 6P
11
Q
rate limiting of HMP shunt
A
glucose 6 phosphate dehydrogenase
XLR
12
Q
regulators of rate limiting of HMP shunt
A
glucose 6 phosphate dehydrogenase XLR
+ NADP
- NADPH
13
Q
rate limiting of de novo pyrimidine synthesis
A
carbamoyl phosphate synthetase II
14
Q
regulators of rate limiting of de novo pyrimidine synthesis
A
carbamoyl phosphate synthetase II
+ ATP
- UDP
15
Q
rate limiting of de novo purine synthesis
A
glutamine-phosphoribosylpyrophosphate (PRPP) amidotransferase
16
Q
regulators of rate limiting of de novo purine synthesis
A
glutamine-phosphoribosylpyrophosphate (PRPP) amidotransferase
- AMP - GMP - IMP
17
Q
rate limiting of urea cycle
A
carbamoyl phosphate synthetase I
18
Q
regulators of rate limiting of urea cycle - cytosol and mito
A
carbamoyl phosphate synthetase I
+ N-acetylglutamine
19
Q
rate limiting of fatty acid synthesis - cytosol
A
acetyl-coA carboxylase (biotin as cofactor)
20
Q
regulators of rate limiting of fatty acid synthesis - cytosol
A
acetyl-CoA carboxylase (biotin as cofactor)
+ insulin + citrate (citrate inhibits glycolysis)
- glucagon - palmitoyl CoA
21
Q
rate limiting of fatty acid oxidation - mito
A
carnitine acyltransferase I
22
Q
regulators of rate limiting of fatty acid oxidation - mito
A
carnitine acyltransferase I
- malonyl CoA
23
Q
rate limiting of ketogenesis - mito
A
HMG CoA synthase
24
Q
regulators of rate limiting of ketogenesis - mito
A
HMG CoA synthase
NONE waddup.
25
rate limiting of cholesterol synthesis - cytosol
HMG CoA reducatase
26
regulators of rate limiting of cholesterol synthesis - cytosol
HMG CoA reductase
+ insulin + thyroxine
- glucagon - cholesterol
27
where does insulin play a regulatory role?
stimulates glycogenesis AND inhibits glycogenolysis
| stimulates cholesterol synthesis
28
where does glucagon play a regulatory role?
inhibits glycogenesis AND stimulates glycogenolysis
| inhibits cholesterol synthesis
29
where does AMP play a regulatory role?
stimulates glycolysis AND inhibits gluconeogenesis
inhibits de novo purine synthesis
stimulates glycogenolysis (wants to get sugar up in er to make ATP)
30
where does ATP play a regulatory role?
inhibits glycolysis AND stimulates gluconeogenesis
inhibits TCA
stimulates de novo pyrimidine synthesis
31
in general, what is NAD+ used asÉ
in catabolic processes to carry away reducing agents as NADH
32
in general, what is NADPH used forÉ
in anabolic processes (fatty acid synthesis and steroid synthesis) as a source of a reducing agent
33
specifically what is NADPH used for times six thingsÉ
1) anabolic processes
2) fatty acid synthesis
3) steroid synthesis
4) glutathione reductase
5) respiratory burst
6) cytochrome P450 -- OH in microsome with CYP2E1
34
compare and contrast hexokinase and glucokinase please
hexokinase - have at tissues that need to get glucose at all times; so has a high affinity/low Km and a low capacity/low Vm; insulin doesn't want to store in these tissues so does not induce its expression; it is inhibited by its downstream product glucose 6 phosphate and is not affected in MODY
glucokinase - on tissues that want to store glucose/use it for regulation ie liver and beta pancreatic cells; therefore has a low affinity/high Km to sense only when glucose is high and has a high capacity/Vm so can keep er coming in when glucose is plentiful; insulin affects storage of glucose thus induces glucokinase expression; it is not inhibited by g6p and is affected in MODY
35
regulation of hexokinase
inhibited by g6P
36
regulation of glucokinase
inhibited by f1P
37
regulation of pyruvate kinase
stimulated by f16bp
| inhibited by ATP and alanine
38
Describe role of fructose 2,6 bisphosphate in the FED state
FED STATE - increased glucagon - increased AC - increased cAMP - increased PKA activity - decreased PFK2 activity - decreased fructose 26 bp - no stimulation of PFK1 AND increased fructose 26bp activity so less fructose 26bp around inhibiting fructose 16 bp -- fructose 6p is converted into glucose 6p for gluconeogenesis
39
Describe role of fructose 2,6 bisphosphate in the FAST state
FAST STATE - increased insulin - decreased AC - decrease cAMP - decreased PKA activity - increased PFK2 activity - increased fructose26bp - increased PFK activity -- glycolysis AND decreased fructose 26bp activity -- more fructose 26bp to inhibit fructose 16bp -- no gluconeogenesis
whhoahh.
40
cofactors required by the pyruvate dehydrogenase complex of enzymes located in the blank for bonus points
mitochondria
1) pyrophosphate; B1; thiamine; TPP
2) FAD; B2; riboflavin
3) NAD; B3; niacin
4) CoA; B5; pantothenic acid
5) lipoic acid
41
what inhibits lipoic acid
arsenic
42
vomiting
garlic breath
0 ATP from glycolysis/TCA
rice water stools
arsenic poisoning
| inhibits lipoic acid (PDH)
43
what are the regulators of PDH
```
increases at exercise where ATP is in demand:
* increased NAD+/NADH ratio
* ADP
* Ca++
inhibited by
*NADH
*ATP
*Acetyl CoA
```
44
what are the only two purely ketogenic amino acids and who cares?
lysine and luecine
| can give to PDH complex deficiency patients.
45
what tissues/cells utilize anaerobic glycolysis as major source of energy?
1. rbc
2. wbc
3. testes
4. kidney medulla
5. lens
6. cornea
46
regulators of isocitrate dehydrogenase
+ ADP
| - ATP - N ADH
47
regulators of alpha-ketoglutarate dehydrogenase
- ATP - NADH - succinyl CoA
48
List the oxidative phosphorylation poisons that directly inhibit the electron transport chain and which complexes they act on.
rotenone- complex I
actinomycin A - complex III
Co and cyanide - complex IV
decrease proton gradient
49
List the oxidative phosphorylation poisons that directly inhibit ATP synthase
oligomycin
| increases proton gradient
50
List the oxidative phosphorylation poisons that are uncoupling agents
2,4 dinitrophenol
aspirin at o/d -- get fever with o/d
thermogenin at brown fat
make inner mitochondrial membrane more permeable so proton gradient is lost; electron transport continues, O2 consumption increases, heat is produced.
*remember Dr Williams and Roho BCHM first termzees in drill**
51
list the irreversible enzymes in gluconeogenesis. include locations and cofactors if applicable
pyruvate carboxylase - ATP, B5 @ mito
PEP carboxykinase - GTP @ cytosol
fructose 1,6 bisphosphatase - @ cytosol
glucose 6 phosphatase - @ ER
52
list the regulators of the irreversible enzymes in gluconeogenesis
pyruvate carbosylase: + acetyl CoA
PEP carboxykinase: none
fructose 1,6 bisphosphatase: +ATP, citrate, NADH -AMP and fructose 1,6 bisphosphate
glucose 6 phosphatase: none
53
why can't muscle participhate in gluconeogenesis?
does not have glucose 6 phosphatase
54
where does the HMP/pentose phosphate pathway occur in the body?
cytosol of a) lactating mammary glands b) liver c) adrenal cortex and d) RBCs
bc this is where glutathione reductase works, or where FA or steroids are produced.
55
clumbs of oxidized/damage Hb in cytoplasm and removal by phagocytosis in the spleen
glucose 6 phosphate dehydrogenase deficiency
Heinz bodies and bite cells
due to lack of glutathione in reduced form bc no NADPH formed to protect and reduced H2O2 to H2O
56
which cells have only aldose reductase not sorbital dehydrogenase and are therefore prone to osmotic damage when sorbitol builds up?
schwann cells
kidney
retina
57
which cells have primarily aldose reductase and some sorbital dehydrogenase and are therefore somewhat prone to osmotic damage by sorbitol buildup?
```
the lens
(schwann cells, retina, kidney have only aldose reductase. boo)
so will see retinopathy, glomerulopathy (my brain cant remember if that's a thing right now... nope that's nephropathy my bad) and neuropathy first before cataracts haha finally makes sense why myelinated neurons are affected first in diabetes - not pain and temp but touch, vibration and proprioception. rant over. oh no its only day three.
```
58
difference between primary and secondary and congenital lactase deficiency please
primary - decreased enzyme with age; prominent in Asians, Africans, native americans
secondary - due to gastroenteritis (rrrooottaa), autoimmune diseases, etc
congenital - rare, due to defective gene - will have normal intestintal biopsy.
59
```
bloating
cramps
flatulence
osmotic diarrhoea
decreased stool pH
increased hydrogen in breath
```
lactase deficiency
60
```
tremor/asterixis
slurring of speech
somnolence
vomiting
cerebral oedema
blurring of vision
MESSY HEAD
```
hyperammonemia
61
how to treat hyperammonemia
limit protein in diet
lactulose - acidifes git and traps NH4+
rifaximin - decreases colonic ammonogenic bacteria
benzoate or phenylbutyrate - bind aa leading to excretion instead of absorption
62
MOA lactulose
acidifies git and traps NH4+
| treatment of hyperammonemia
63
MOA rifixamin
decreases colonic ammonogenic bacteria
| treatment of hyperammonemia
64
MOA benzoate and phenylbutyrate
bind to aa leading to excretion instead of absorption
| treatment of hyperammonemia
65
```
how do you treat this disease:
intellectural disability
osteoporosis
marfanoid habitus
kyphosis
lens subluxation (down and in)
thrombosis
atherosclerosis (stroke and MI risk)
```
homocysteniuria
a) cystathione synthase def -- cysteine, B12 and folate
b) decreased affinity of cystathionine synthase for B6 -- increase B6 and cysteine in diet
c) methionine synthase/homocystein methyltransferase def -- increased methionine in diet
66
how do you treat cystinuria?
good hydration and make cystine stones more soluble
a) urinary alkalinisation with acetazolamide or potassium citrate
b) chelating agents - penicillamine
67
diagnostic test for cystinuria
urinary cyanide-nitroprusside test
| UWORLD Q I GOT WRONG> no more.
68
```
severe fasting hypoglycemia
increased glycogen in liver
increased blood lactate
increase uric acid
increased TAGs
hepatomegaly
```
Von Gierkes disease
type I glycogen storage disease
AR
glucose-6-phosphatase
69
```
cardiomegaly
hypertrophic cardiomyopathy
exercise intoleranc
systemic findings
trashed heart, liver, muscle
```
```
Pompe disease
type II glycogen storage disease
AR
acid maltase
lysosomal alpha 1,4 glucosidase
```
70
gluconeogenesis intact
lactate levels normal
milder of: hyperglycemia, uric acid, TAGS, hepatomegaly
Cori disease
type III glycogen storage disease
AR
alpha 1,6 glucosidase
71
```
increased glycogen in muscle
painful muscle cramps
myoglobinuria with strenuous exercise
arrhythmias from electrolyte disturbances
normal glucose levels
```
mcArdle
type V glycogen storage disease
AR
skeletal muscle glycogen phosphorylase/myophosphorylase
72
Fabry - enzyme, build up, inheritance
alpha-galactosidase A - ceramide trihexoside - XLR
73
Gaucher - enzyme, build up, inheritance
glucocerebrosidase - glucocerebroside - AR
74
Niemann Pick - enzyme, build up, inheritance
sphingomyelinase - sphingomyelin- AR
75
Tay Sach - enzyme, build up, inheritance
hexoaminosidase A - Gm2 ganglioside - AR
76
Krabbe disease - enzyme, build up, inheritance
galactocerebrosidase - galactocerebroside, psychosine - AR
77
Metachromatic luekodystrophy - enzyme, build up, inheritance
arylsulfatase - cerebroside sulfatase - AR
78
hurler - enzyme, build up, inheritance
alpha-L-iduronidase - heparan sulfate, dermatan sulfate AR
79
hunter - enzyme, build up, inheritance
iduronate sulfatase - heparan sulfate, dermatan sulfate XLR
80
peripheral neuropathy of hands and feet
cardiovascular disease
renal disease
angiokeratomas
fabrys - XLR - alpha-galactosidase-A, ceramide trihexoside
81
which lysosomal storage disease is the most common?
gaucher
82
hepatomegaly
pancytopenia
osteoporosis
bone crises
gaucher - AR - galactocerbrosidase - galactocerbroside
BONE and LIVER
no CNS/no cherry macula
gift wrap cells
83
progressive neurodegeneration
hepatosplenomegaly
cherry red spot on macula
niemann pick - AR - spingomyelinase - sphingomyelin
CNS and LIVER
cherry macula
lipid laden foam cells
84
progressive neurodegeneration
developmental delay
cherry red spot
NO hepatosplenomegaly
tay sach - AR - hexoaminosidase A - Gm3 ganglioside
no liver
CNS
onion skin cells
85
peripheral neuropahy
developmental delay
optic neuropathy
krabb disease - AR - alpha-galactocerbrosidase - galactocerebroside, psychosie
globoid cells
86
central and peripheral demyelination
ataxia
dementia
metachromatic leukodystrophy - AR - arylsulfatase - cerebroside sulfate
87
```
developmental delay
gargoylism
airway obstruction
hepatosplenomegaly
corneal clouding
```
hurler - alpha-L-iduronidase - AR
88
```
MILDER
developmental delay
gargoylism
airway obstruction
hepatosplenomegaly
NO corneal clouding
aggressive behaviour
```
hunter - iduronate sulfatase - heparan sulfate, dermatan sulfate - XLR
89
weakness
hypotonia
hypoketotic hypoglyceia
systemic primary carnitine deficiency
90
```
vomiting
lethargy
coma
seizures
liver dysfunction
hypoketotic hypoglycemia
increased 8-10 carbon fatty acyl carnitines in blood
```
medium-chain acyl-CoA dehydrogenase deficiency
| AR
