6. Metabolism 2 Flashcards
1
Q
what enzyme converts phenylalanine to tyrosine? what cofactor is used?
A
phenylalanine hydroxylase; tetrahydrobiopterin factor
2
Q
what converts tyrosine to DOPA? what cofactor is used?
A
tyrosine hydroxylase; tetrahydrobiopterin factor; NADP+
3
Q
what is dihydroxyphenylalanine ?
A
DOPA
4
Q
T/F tyrosinase converts tyrosine to DOPA
A
false; tyrosine hydroxylase
5
Q
which catecholamine has inhibitory action against acetylcholine?
A
dopamine
6
Q
what converts dihydrobioterin back to tetrahydrobioterin factor? what energy carrier is used? in what reactions is this cofactor used?
A
dihydropterin reductase; NADP+; phenylalanine to tyrosine and tyrosine to DOP
7
Q
what converts dopa to dopamine? using what cofactor?
A
dopa decarboxylase; B6
8
Q
where does catecholamine synthesis take place?
A
neural tissue and adrenal medulla
9
Q
what converts dopamine to norepinephrine? using what cofactor?
A
dopamine beta hydroxylase; vit C
10
Q
T/F vit c is needed in catecholamine synthesis
A
true! dopamine to norepinephrine
11
Q
what negatively regulates dopamine to norepinephrine?
A
carbidopa
12
Q
what enzyme converts norepinephrine to epinephrine? using what cofactor?
A
phenylethanolamine N-methyl transferase; SAM
13
Q
what is phenylethanolamine N-methyl transferase located?
A
adrenal medulla
14
Q
T/F phenylethanolamine N- methyl is only located in the adrenal medulla
A
true (epinephrine only made in the medulla)
15
Q
what is the degradation product of Norepinephrine?
A
VMA
16
Q
what is the degradation product of dopamine?
A
HVA
17
Q
what is the degradation product of epinephrine?
A
metanephrine
18
Q
what two def. most commonly cause phenylketonuria?
A
phenylalanine hydroxylase or tetrahydrobiopterin factor
19
Q
what two enzymes are in involved in catecholamine degradation?
A
COMT and MAO
20
Q
what aa becomes essential with phenylketonuria?
A
tyrosine
21
Q
what explains the excess phenylketones in the urine in phenylketonuria?
A
phenylalanine build up
22
Q
give an example of how phenylketonuria is pleiotropic.
A
also have fair skin, blond hair, blue eyes, eczema
23
Q
what are the findings with phenylketonuria?
A
mental and growth retardation; seizures, fair skin, eczema, musty body odor; neurotoxic ketones and acids stimulate vomitting- can lead to pyloric stenosis
24
Q
what is the treatment for phenylketonuria?
A
decreased phenylalanine, increase tyrosine
25
what is Maternal PKU?
lack of proper dietary therapy during pregnancy resulting in infant's microcephaly, mental retardation, growth retardation and congenital heart defects
26
what type of aa is phenylalanine? what implications does this have on the presentation of phenylketonuria?
aromatic; musty body odor
27
what are phenylacetate, phenylactate, and phenylpyruvate?
phenylketones that build up in phenylketonuria
28
what is the mode of inheritance of phenyketonuria?
AR
29
when is phenylketonuria screened? why?
2-3 days after birth because maternal enzyme during fetal like might still be there
30
what does a deficiency in homogentistic acid oxidase result in? what is this also known as?
alkaptonuria; ochronosis
31
what enzyme is involved in the degradation of tyrosine to fumarate?
homogentistic acid oxidase
32
what builds up in the urine in homogentistic acid oxidase deficiency? what does this result in ?
urine turns black on standing
33
what are the findings in alkaptonuria? why do they occur?
dark connective tissue, brown pigmented sclera, debilitating athralgias; homogentistic acid builds up and can be toxic to cartilage
34
name three causes of albinism. what does albinism increased risk of?
tyrosinase deficiency; defective tyrosine transporters; lack of migration of neural crest cells; skin cancer
35
T/F Albinism is AR
false; only the tyrosinase one is- albinism has variable heritability because of locus heterogeneity
36
T/F Ocular albinism is AR
false- X linked recessive
37
T/F homocysteine gets turned into methionine by homocysteine transferase
TRUE
38
other than being returned to methionine, what else is the fate of homocysteine? through what enzyme? with what cofactor?
cystathionine (which then goes to cysteine) via cystathionine reductase; B6
39
what does SAM turn into after it loses a methyl? how does it get turned back to SAM?
homocysteine; homocysteine methyltransferase with B12 and tetrahydrofolate
40
what three enzyme def. can cause homocysteinura? what is their mode of inheritance?
homocysteine methyltransferase, cystathionine reductase, decreased affinity of cystathionine reductase for pyridoxal phosphate; AR
41
what aa becomes essential with homocystinuria? phenylalaninuria?
cysteine; tyrosine
42
how do you treat homocystinuria due to decreased affinity of cystathionine reductase to B6?
by giving high amounts of pyridoxal phosphate in the diet
43
what are the findings of homocystinuria?
increased homocysteine in the urine, mental retardation, osteoporosis, marfanoid habitus, and atherosclerosis
44
what aa degradation disorder results in atherosclerosis? debiltating arthralgias? osteoporosis?
homocystinuria (homocysteine damages endothelial cells); alkaptonuria (tyrosine degradation); homocystinuria
45
what is the product of odd chain fatty acid synthesis? how does it return to TCA cycle? what cofactor is required?
proprionyl coA; through methylmalonyl coA; B12
46
what is cystinuria due to?
hereditary defect of renal tubular amino acid transporter for cysteine , ornithine, lysine and arginine in the PCT of kidnyes
47
what is the presentation for cystinuria?
cystine kidney stones (cystine staghorn calculi)
48
what is the treatment for cystinuria?
acetazolamide to alkalinize the urine
49
T/F cysteine is a dimer
true- of two dimers connected by disulfide bond
50
what enzyme is necessary for branched aa degradation? what cofactor? what are the branched aa?
branche aa alpha ketoacid dehydrogenase; thiamine; Isoleucine, leucine, valine
51
what builds up in the blood of patients with maple syrup urine disease? urine/poo? what does this cause?
alpha ketoacids in the blood; alpha keto acids in the urine/poo smells of maple syrup/burnt sugar
52
what enzyme is deficient in maple syrup urine disease?
branched alpha ketoacid dehydrogenase
53
what are the findings in maple syrup disease? what should be tried to be given as treatment?
CNS defects, mental retardation, death, feeding difficulties, vomiting, hypoglycemia; thiamine
54
what is hartnup disease? what is the mode of inheritance?
defective neutral amino acid transporter on renal and intestinal cells; AR
55
what aa is most accumulated in hartnup disease? what vitamin becomes deficient?
tryptophan; niacin
56
what is the main clinical presentation of hartnup disease?
pellagra
57
what is the main hormonal regulation of glycogen?
glucagon, insulin and epinephrine
58
T/F the main hormonal regulation of glycogen is glucagon and insulin
false- glucagon, insulin and epinephrine
59
where is glycogen mainly found?
liver and skeletal muscle
60
what is the main use of glycogen?
reserve supply of glucose in the fasting state- liver gives to the blood and skeletal muscle uses for itself
61
T/F increased levels of cAMP results in glycogenolysis
TRUE
62
T/F glucagon works on the liver and muscle to activate glycogenolysis by activating adenylyl cyclase
false- just liver
63
T/F epinephrine works on liver to activate glycogenolysis by activating adenylyl cyclase
false- liver and muscle
64
T/F phosphorylated glycogen phosphorylase is inactive
FALSE
65
what is the first enzyme step in glycogenolysis? what activates it ? inactivates?
glycogen phosphorylase; phosphorylation and dephosphorylation
66
how does glucagon activate glycogenolysis? what regulator does similar?
by activating adenylyl cylase which increases cAMP which increases levels of protein kinase A which activates glycogen phosphorylase kinase; epinephrine
67
how is muscle activity and glycogenolysis coupled in muscle?
calcium and calmodulin activate glycogen phosphorylase kinase
68
T/F inuslin downregulates glycogenolysis by inactivating cAMP
false- insulin receptor is not cAMP second receptor but rater tyrosine kinase- which dimerizes and activates a protein phosphatase which de phosphorylates glycogen phosphorylase
69
how does insulin both deactivate glycogenolysis and activates glycogenesis at same time?
by activating protein phosphatase which both dephosphorylates glycogen phosphorylase (deactivating) and dephosphorylates glycogen synthase (activating it )
70
T/F insulin acts on the liver to deactivate glycogenolysis
false- both liver and muscle (unlike glucagon)
71
T/F glycogen branches have 1,4 bonds and linkages have 1,6 bonds
false-opposite
72
T/F glycogenolysis in skeletal muscle maintains blood sugar
false; in hepatocytes
73
what kind of linkages does glycogen synthase make? branching enzyme?
alpha 1,4 linkages; alpha 1,6 linkages
74
why does branching occur in glycogenesis?
branching increases the rate of synthesis and breakdown of glycogen by having more sites to add on to and break off
75
after glucose 6 P is converted to glucose 1 P , what is the next step in glycogenesis? then what?
conversion to UDP glucose via UDP glucose pyrophosphorylase; glycogen synthase (rate limiting step )
76
what is the main form of glycogenolysis after glycogen phosphorylase? what happens instead in some lysosomes? does this process use glycogen phosphorylase? in what disease is this enzyme deficient?
debranching enzyme; alpha 1, 4 glucosidase; no!; Pompes disease
77
what does glycogen phosphorylase in glycogenolysis create?
limit dextrans
78
what are the glycogen storage disease? what they result in?
abnormal glycogen metabolism results in accumulation of glycogen in cells
79
T/F all the glycogen storage diseases are AR
TRUE
80
what is the fate of glucose from glycogenolysis?
glucosekinase to glucose 6 P
81
how do hepatocytes release glucose 6 P from glycogenolysis into the blood ? in what disease is this enzyme deficient?
with glucose 6 phosphatase; Von Gierkes disease
82
what is the deficient enzyme in Von Gierkes disease? what are the findings?
severe fasting hypoglycemia, very high levels glycogen in liver, high blood lactate, hepatomegaly
83
what is the order of types of glycogen storage disease?
Very Poor Carb Metabolism (Von Gierke- Type 1, Pompes- Type II, Cori's- Type III, McArdles disease- Type IV)
84
What are the findings for Pompe's disease? what is the deficient enzyme?
cardiomegaly and systemic findings leading to early death; lysosomal alpha-1,4-glucosidase (acid maltase)
85
Findings for Cori's disease? deficient enzyme?
milder form of type 1 with normal blood lactate levels; debranching enzyme (alpha-1,6 glucosidase)
86
findings for McArdle's disease? deficient enzyme?
high glycogen in muscle, but cannot break it down, leading to painful muscle cramps, myoglobinuria with strenuous exercise, no increase in lactic acid after exercise; skeletal muscle glycogen phophorylase
87
which glycogen storage disease results in hepatomegaly?
von gierkes
88
which glycogen storage disease causes hypertriglyceridemia?
von gierkes
89
which glycogen storage disease results cardiomegaly?
pompes
90
T/F coris glycogen storage disease has normal lactate levels
TRUE
91
which glycogen storage disease results in no lactic acid after exercise?
mcardles disease
92
what causes the lysosomal storage diseases?
deficiencies in one of the many lysosomal enzymes results in accumulation of abnormal metabolic products
93
which two lysosomal storage disease are XR and not AR?
Fabrys Disease and Hunters Syndrome
94
what is the deficient enzyme in Fabry's disease? accumulated Substrate?
alpha galactosidase A; ceramide trihexoside
95
what is the deficient enzyme in Gauchers disease? accumulated Substrate?
Beta glucocerebrosidase; glucocerebroside
96
what is the deficient enzyme in Niemann Pick disease? accumulated Substrate?
Sphingomyelinase; sphingomyelin
97
what is the deficient enzyme in Tay Sachs disease? accumulated Substrate?
Hexosaminidase A; GM2 ganglioside
98
what is the deficient enzyme in Krabbes disease? accumulated Substrate?
Galactocerebrosidase; Galactocerebroside
99
what is the deficient enzyme in Metachromatic leukodystrophy disease? accumulated Substrate?
arylsulfatase A; cerebroside sulfate
100
what is the findings in Fabrys disease?
peripheral neuropathies of hands/feet; angiokeratomas between umbilicus and knees; cardiovascular/renal disease
101
which is the most common lysosomal storage disease? what are its findings?
Gauchers; hepatosplenomegaly, aseptic necrosis of the femur, bone crises, Gauchers cells -crumpled tissue paper looking (fibrillar appearing macrophages in liver, spleen, b.m.)
102
what are the findings in Niemann Pick disease?
progressive neurodegeneration (spasticity d/t UMN disease), hepatosplenomegaly, cherry red spot on macula, foam cells
103
what are the findings in Tay Sachs disease?
progressive neurodegeneration (spasticity d/t UMN disease), NO hepatosplenomegaly, cherry red spot on macula, lysosomes with onion skin, muscle weakness
104
what are the findings in Krabbes disease?
peripheral neuropathy, developmental delay, optic atrophy, globoid cells
105
what are the findings in Metachromatic leukodystrophy?
central and peripheral demyelination with ataxia and dementia
106
which two lysosomal storage diseases findings are very similar? how do you differentiate them?
Niemann pick and Tay Sachs; hepatosplenomegaly or not
107
what are the mucopolysaccharidoses? which one is XR? AR? what accumulates in them?
Hurlers Syndromes;Iduronate sulfatase deficiency; alpha L iduronidase def; heparan sulfate, dermatan sulfate
108
which Hurlers is milder and presents with no corneal clouding?
XR - iduronate sulfatase
109
what are the findings in AR Hurlers?
developmental delay, gargoylism, airway obstruction (d/t short neck), corneal clouding, CAD, hepatosplenomegaly
110
what lysosomal storage diseases are seen more in Ashkenazi Jew?
tay Sachs, Niemann Picks, Gauchers
111
why is there hepatosplenomegaly in many of the lysosomal storage diseases?
because cells of mononuclear phagocytic are esp rich in lysosomes
112
which lysosomal storage diseases have enzymes that are def in cells that are neuronal mostly?
neimann pick and tay sachs
113
in Fabrys, what accumulates in tissue because fibroblasts express the def enzyme highly?
ceramide trihexoside
114
what is the first step in fatty acid synthesis? where does it occur? where does triacylglycerol synthesis occur?
citrate shuttle in the inner mitochondrial membrane transports acetyl coA into the cytoplasm; liver; liver and adipose tissue
115
what is the rate limiting step in fatty acid synthesis? what four things inhibit this rate limiting step? what stimulates it?
acetyl coA carboxylase converting Acetyl coA into malonyl coA; increased AMP, glucagon, epinephrine, palmitate; citrate
116
where does synthesis of longer chain fatty acids occur? what does it require?
SER and mitochondria; NADPH
117
what is palmitate? saturated or unsaturated? what does that meat?
a 16C FA! the product in FA synthesis; saturated; no double bonds
118
T/F fatty acid synthase requires NADP+
false! NADPH- reductive biosynthesis!
119
what cofactor does acetyl coA carboxylase require? what does it convert?
biotin; rate limiting step in fA synthesis- acetyl coA into malonyl coA
120
T/F carnitine shuttle is used to transport acetyl coA out of the mitochondria for fatty acid synthesis
false! citrate shuttle; carnitine shuttle takes acyl coA into the mit for fatty acid degradation
121
what does lipolysis generate? and what two regulators activate lipases?
triacylglycerols in adipose tissue broken down into glycerol and free fatty acids; growth hormone and epinephrine
122
what is the fate of the two products of lipolysis?
glycerol goes to liver for gluconeogenesis; free fatty acids bind to albumin in blood and travel to cells to be used as for energy
123
T/F Fatty acid coA synthetase is used in FA synthesis
false- FA degradation
124
what is the first step in FA degradation in the cytosol?
FA coA synthetase combines coA with FA to make acyl coA
125
what is required to get Acyl coA in FA degradation into the mitochondria for beta oxidation to acetyl coA groups?
carnitine shuttle
126
what is carnitine deficiency and what does it result in?
inability to transport LCFA into mitochondria results in their build up and causes weakness, hypotonia AND HYPOKETOTIC HYPOGLYCEMIA
127
what is deficient in someone with hereditary hypoketotic hypoglycemia?
carnitine shuttle
128
why does fa degradation occur in the mitochondria? what does FA degradation produce? what is the fate of this product?
because that is where the products will be consumed; acetyl coA; TCA cycle of ketone body production
129
what is acyl coA dehydrogenase used in? what does a deficiency in this enzyme produce?
fatty acid (acyl coA) oxidation to acetyl coA; increase in dicarboxylic acids, and decreased glucose and ketones
130
walk through the process that adipose tissue makes triacylglycerol.
lipoprotein lipases take FA from VLDL and chylomicrons which are then combined with glycerol 3 P (a carb intermediate) to make triacylglycerol
131
what is the main source of FA? where else can they be released from?
synthesis in liver and then hydrolysis of chylomicrons and VLDLs by capillary lipoprotein lipase in peripheral tissue; adipose tissue by lipases
132
T/F the liver uses ketone bodies for energy
false- only muscle and brain have transferase enzyme that converts ketone bodies to acetyl coA
133
where are ketone bodies made? what is the rate limiting enzyme? what are they made from?
mitochondria in liver; HmG CoA synthetase; amino acids and beta oxidation of FA
134
what does the brain do with ketone bodies?
metabolizes them with transferase enzymes to acetyl coA
135
what are three ketone bodies? which is not detected in urine? which do you see most in alcoholic ketoacidosis?
b hydroxybutyrate, acetone, acetoacetate; beta hydroxybutyrate; beta hydroxybutyrate
136
what is the impetus for ketoacidosis in starvation? alcoholism?
oxaloacetate depleted for gluconeogenesis; excess NADH shunts oxaloactetate towards malate
137
what causes fruity odor in ketoacidosis?
acetone
138
how many calories does one gram of protein generate? carb? fat?
4,4,9
139
T/F HMG coA reductase is used in KB synthesis
false- HMG coA synthase; cholesterol synthesis uses HMG coA reductase
140
in a 100 meter sprint what is used as energy? in general what is the rule with exercise? what is used in 1000 meter run?
Stored ATP, creatine phosphate, anaerobic glycolysis; as distances increase, ATP is obtained from additional resources; above plus ox phos
141
what is used in a marathon?
glycogen and FFA oxidation- glucose conserved for final sprinting!
142
what are the priorities in fasting and starvation?
to supply sufficient glucose to the brain and the RBCs and to preserve protein
143
what is the source of ATP after a meal?
glycolysis and aerobic respiration
144
what is the source of ATP when you are fasting (in between meals)?
hepatic glycogenolysis (mostly), also hepatic gluconeogenesis, adipose release of FFA (minor)
145
after how long of starvation do glycogen reserves deplete? after this occurs, how are blood glucose levels maintained?
1 day; adipose release of FFA, hepatic gluconeogenesis from peripheral tissue lactate and alanine and from adipose tissue glycerol and propionyl coA
146
what does adipose tissue contribute for hepatic gluconeogenesis during starvation? muscle?
glycerol and propionyl coA; lactate and alanine
147
after day 3 of starvation, what is the main source of energy?
adipose tissue for brain and heart (ketone bodies) and then go to vital protein degradation (organ failure)
148
what is the rate limiting step in cholesterol synthesis? what does it do?
HMG CoA reductase; converts HMG CoA to mevalonate
149
how much of plasma cholesterol is esterified? and by what?
2/3; LCAT (lecithin cholesterol acyltransferase)
150
what do statins inhibit?
HMG CoA reductase
