Biochemistry First Aid- Metabolism Part 1 (98-106) Flashcards
1
Q
name four major metabolic processes that take place in the mitochondria
A
fatty acid oxidation (beta oxidation), acetyl CoA production, the TCA cycle, and oxidative phosphorylation
2
Q
what major metabolic processes occur in the cytoplasm (try to name 6)
A
glycolysis, HMP shunt, fatty acid synthesis, protein synthesis (RER), steroid synthesis (SER), cholesterol synthesis
3
Q
name three metabolic processes that occur both in the mitochondria and in the cytoplasm
A
heme synthesis, urea cycle, gluconeogenesis
4
Q
define the term kinase
A
an enzyme that uses ATP to phosphorylate a substrate
5
Q
define the term phosphorylase
A
an enzyme that phosphorylates a substrate without using ATP
6
Q
define the term dehydrogenase
A
an enzyme that catalyzes redox reactions
7
Q
define the term hydroxylase
A
an enzyme that adds a hydroxyl group to a substrate
8
Q
define the term carboxylase
A
an enzyme that transfers CO2 groups with the help of biotin
9
Q
define the term mutase
A
an enzyme that relocates a functional group within a molecule
10
Q
what is the rate limiting step of glycolysis and what enzyme catalyzes it?
A
conversion of F6P to fructose-1,6-bisphosphanate
catalyzed by phosphofructokinase-1 (PFK-1)
11
Q
what molecules promote or inhibit phosphofructokinase-1 activity?
A
promote: AMP and fructose-2,6-bisphosphate
inhibit: ATP and citrate
12
Q
what enzyme catalyzes the rate-limiting step of gluconeogenesis? what is the rxn?
A
fructose-1,6,-bisphosphatase, which converts fructose-1,6,-bisphosphate to F6P
13
Q
what molecules positively and negatively regulate fructose-1,6,-bisphosphatase?
A
positive: ATP and acetyl-CoA
negative: AMP and fructose-2,6-bisphosphate
14
Q
what is the rate limiting reaction and enzyme of the TCA cycle?
A
conversion of isocitrate to alpha-ketoglutarate catalyzed by isocitrate dehydrogenase
15
Q
what molecules positively and negatively regulate isocitrate dehydrogenase?
A
positive: ADP
negative: ATP and NADH
16
Q
what is the rate limiting reaction and enzyme of glycogenesis?
A
addition of UDP-glucose to glycogen catalyzed by glycogen synthase
17
Q
what are the negative and positive regulators of glycogen synthase
A
positive: G6P, insulin, cortisol
negative: epinephrine, glucagon
18
Q
what is the rate limiting reaction and enzyme of glycogenolysis?
A
release of glucose-1-phosphate from glycogen catalyzed by glycogen phosphorylase
19
Q
what are the positive and negative regulators of glycogen phosphorylase?
A
positive: epinephrine, glucagon, AMP
negative: G6P, insulin, ATP
20
Q
what is the rate limiting reaction and enzyme of the HMP shunt?
A
conversion of G6P to 6-phosphogluconolactone catalyzed by G6PD
21
Q
what molecules are the positive and negative regulators of G6PD?
A
positive: NADP+
negative: NADPH
22
Q
what is the rate limiting reaction and enzyme for de novo pyrimidine synthesis
A
glutamine + CO2 conversion to carbamoyl phosphate catalyzed by carbamoyl phosphate synthetase II
23
Q
what is the rate limiting enzyme for de novo purine synthesis
A
PRPP amidotransferase
24
Q
what are the negative regulators of PRPP amidotransferase
A
AMP, inosine monophosphate (IMP), GMP
25
what enzyme catalyzes the rate limiting step of the urea cycle
carbamoyl phosphate synthetase I
26
what molecule upregulates the urea cycle
N-acetylcysteine
27
what enzyme catalyzes the rate limiting step in the fatty acid synthesis pathway
Acetyl-CoA carboxylase (ACC)
28
what molecules positively and negatively regulate fatty acid synthesis?
positive: insulin, citrate
negative: glucagon, palmitoyl-CoA
29
what enzyme catalyzes the rate limiting step of fatty acid oxidation
acetyl-CoA acyltransferase I
30
what molecule negatively regulates fatty acid oxidation?
malonyl-CoA
31
what enzyme catalyzes the rate limiting step in ketogenesis
HMG-CoA synthase
32
what enzyme catalyzes the rate limiting step in cholesterol synthesis
HMG-CoA reductase
33
what molecules upregulate and downregulate cholesterol synthesis
upregulate: insulin and thyroxine
downregulate: glucagon and cholesterol
34
how many net ATP molecules does aerobic metabolism produce in the heart and liver?
in the muscle?
in heart and liver via malate-aspartate shuttle: 32
in muscle via glycerol-3-phosphate shuttle: 30
35
how does arsenic affect energy production?
arsenic causes glycolysis to produce zero net ATP (also uncouples oxidative phosphorylation)
36
how many ATP molecules are produced by anaerobic glycolysis
2 net ATP per glucose
37
what are CoA and lipoamide carriers of
acyl groups
38
what general rxn does biotin carry out
carboxylation
39
what do tetrahydrofolates carry
1-carbon groups
40
what does S-adenosyl methionine (SAM) carry
methyl groups
41
what does thiamine pyrophosphate (TPP) carry
aldehydes
42
NADP+ is generally used in _________ processes while NADPH is used in _________ processes
NADP+ is generally used in catabolic processes (to accept reducing equivalents) while NADPH is used in anabolic processes to supply reducing equivalents
43
what major processes use NADPH
anabolic processes, respiratory burst, cytochrome P450, glutathione reductase
44
differentiate hexokinase from glucokinase in terms of location, affinity, Vmax and insulin induction
hexokinase: in most tissues, but not liver nor beta cells of pancreas, lower affinity for glucose, lower Vmax, not induced by insulin
glucokinase: in liver and beta cells, higher affinity for glucose, higher Vmax, induced by insulin
45
is hexokinase or glucokinase feedback inhibited by G6P
hexokinase
46
is hexokinase or glucokinase gene mutation associated with the maturity-onset diabetes of the young
glucokinase
47
list the reactants and products of the glycolysis net reaction
Glucose + 2Pi + 2ADP+ NAD -->
| 2 pyruvate + 2ATP + NADH + 2H+ + 2H2O
48
which steps of glycolysis require ATP
glucose---> G6P (catalyzed by hexo/glucokinase)
| F6P---> F-1,6-BP (catalyzed by PFK-1)
49
which steps of glycolysis makes ATP
1,3-BPG ---> 3-phosphoglycerate (catalyzed by phosphoglycerate kinase)
PEP ---> pyruvate (catalyzed by pyruvate kinase)
50
list the the molecules in the steps of glycolysis
glucose---> G6P ---> F6P ---> F-1,6-BP ---> Glyceraldehyde-3P and DHAP (DHAP gets converted to Glyceraldehyde-3P) --->
1,3-bisphosphoglycerate ---> 3-phosphoglycerate ---> 2-phosphoglycerate ---> phosphoenolpyruvate (PEP) ---> pyruvate
51
what's the relationship between FBPase-2 and phosphofructokinase-2
FBPase-2 and phosphofructokinase-2 are parts of the same bifunctional enzyme. Which activity the enzyme performs depends on phosphorylation by protein kinase A.
52
how is F2,6-BP regulate glucose in the fasting state
increased glucagon --> increased cAMP --> increased PKA --> increased FBPase-2 --> decreased PFK-2, leading to less glycolysis and more gluconeogenesis
53
what two metabolic pathways does pyruvate dehydrogenase complex link
glycolysis and TCA cycle
54
what are the reactants and products in the reaction catalyzed by pyruvate dehydrogenase complex
pyruvate + NAD + CoA ---> AcetylCoA +NADH + CO2
55
what are the 5 cofactors that are needed for the pyruvate dehydrogenase complex to function
1. pyrophosphate (TPP from thiamine aka B1)2. FAD (from riboflavin aka B2)3. NAD (from niacin aka B3)4. CoA (from panthenate)5. Lipoic acid
56
what stimulus upregulates activity of the pyruvate dehydrogenase complex and via what molecular changes
exercise causes increased NAD/NADH ratio, increased ADP, and increased calcium (stimulators of pyruvate dehydrogenase complex activity)
57
the pyruvate dehydrogenase complex is similar to what other enzyme
alpha-ketoglutarate dehydrogenase (they have the same cofactors, similar substrate and similar mechanism of action)
58
what inhibits lipoic acid
arsenic
59
what are the symptoms of arsenic poisoning
vomiting, rice-water stools, garlic breath
60
what molecules build up as a result of pyruvate dehydrogenase complex deficiency
pyruvate buildup leads to shunting to lactate (via LDH) and alanine (via ALT)
61
what is the clinical presentation of pyruvate dehydrogenase complex deficiency
neurologic defects, lactic acidosis, increased serum alanine starting in infancy
62
how is pyruvate dehydrogenase complex deficiency treated
increased intake of ketogenic nutrients (i.e. high fat content or increased lysine and leucine, which are the only purely ketogenic amino acids)
63
explain the four different ways that pyruvate can be metabolized
1. into alanine catalyzed by alanine amintransferase (cofactor=B6)2. into oxaloacetate catalyzed by pyruvate carboxylase (cofactor=biotin)3. into acetyl-CoA catalyzed by pyruvate dehydrogenase (cofactors=B1,B2,B3,B5,lipoic acid)4. into lactic acid catalyzed by lactate dehydrogenase (cofactor=B3)
64
what is generated as a result of the TCA cycle (per acetyl-CoA molecule)how many ATP molecules does this eventually translate into
3 NADH, 1 FADH2, 2 CO2, 1 GTP (per acetyl CoA molecule)==> 10 ATP (per acetyl CoA molecule)
65
list the enzymes in the TCA cycle from right after entry of Acetyl-CoA until completion of a cycle
acetyl-CoA--> citrate--> isocitrate --> alpha-ketoglutarate --> succinyl-CoA --> succinate --> fumarate --> malate --> oxaloacetate
66
name three enzymes in the TCA cycle that catalyze irreversible reactions
isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, citrate synthase
67
how do NADH electrons from glycolysis enter the mitochondria
via the malate-aspartate shuttle or via the glycerol-3-phosphate shuttle
68
to what complex in the inner mitochondrial membrane are NADH electrons transferred?what about FADH2?
NADH at complex 1FADH2 at complex 2
69
explain how the electron chain and oxidative phosphorylation drive ATP production (briefly summarize the pathway)
electrons from NADH and FADH2 are transferred to complexes 1 and 2 in the inner mitochondrial membrane leading to a build up of protons in the intermembrane space; protons rush into the mitochondrial matrix via complex 5 and this movement of H+ down its gradient is coupled to phosphorylation of ADP to make ATP
70
ATP produces how many ATP per NADH?how many per FADH2?
2.5 ATP per NADH1.5 ATP per FADH2
71
name four inhibitors of electron transport chain;how do they work?
rotenone, cyanide, antimycin A and CO directly inhibit electron transport leading to low proton gradient and low ATP synthesis
72
what electron transport complex does rotenone inhibit and therefore what electron carrier is directly affected
complex 1; transfer of electrons from NADH is blocked
73
what electron transport complex is blocked by antimycin A
Complex 3
74
what molecules inhibit complex 4 of electron transport chain
cyanide and CO
75
what molecule directly inhibits mitchondrial ATP synthase;what happens to the proton gradient across the inner mitochondrial membrane as a result
oligomycin;H+ gradient increases (causing electron transport to stop)
76
what are some uncoupling agents and how do they work
2,4-dinitrophenol, aspirin, thermogenin in brown fat;they increase the permeability of the inner mitochondrial membrane leading to lower proton gradient and higher O2 consumption --> ATP synthesis stops, but electron transport continues (produces heat instead)
77
what is 2,4-dinitrophenol used for
used illicitly for weight loss
78
name the irreversible enzymes of gluconeogenesis
("pathway produces fresh glucose") pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase, glucose-6-phosphatase
79
what reaction does pyruvate carboxylase catalyze, where does it occur, and what is needed for the reaction to happen (cofactors and activators)
pyruvate -->oxaloacetate;occurs in mitochondria;requires biotin and ATP, activated by acetyl-CoA
80
what reaction does PEP carboxykinase catalyze;where does it occur;what is required
oxaloacetate --> PEP;takes place in the cytosol;GTP is required
81
what reaction is catalyzed by F-1,6-bisphosphatase; where does it occur;what upregulates and downregulates this reaction
F-1,6-BP--> F-6-P;occurs in the cytosol;upregulated by citrate, downregulated by F-2,6-BP
82
what reaction does G-6-phosphatase catalyze;where does it occur
G-6-P;occurs in the ER
83
where does gluconeogenesis predominantly occur and why
in the liver; to maintain euglycemia in states of fasting
84
besides the liver where else are enzymes of gluconeogensis found
kidney and intestinal epithelium
85
why can't the muscle do gluconeogenesis
it lacks G-6-phosphatase
86
how can odd chain fatty acids get converted to glucose
odd chain fatty acids yield 1 proprionyl-CoA during metabolism which enters the TCA cycle as succinyl-CoA --> oxaloacetate and undergoes gluconeogenesis
87
why can't even-chain fatty acids yield new glucose
even-chain fatty acids get metabolized to acetyl-CoA, which cannot enter the pathway for gluconeogenesis
88
what is the purpose of the HMP (hexose monophosphate) shunt
to use G-6-P to generate NADPH (used as a reducing agent i.e. for glutathione, fatty acid synthesis and cholesterol synthesis)
89
what are the end products of the HMP shunt
NADPH, ribose (can be used for DNA synthesis or glycolytic intermediates)
90
where does the HMP shunt take place (what cellular location)
in the cytoplasm
91
how much ATP does the HMP shunt use?how much ATP does the HMP shunt produce?
trick question!: none and none!
92
in what tissues of the body use the HMP shunt
lactating mammary glands, liver, adrenal cortex, RBC's
93
what are the two phases of the HMP shunt and which phase is reversible
two phases: oxidative and nonoxidativethe nonoxidative phase is reversible
94
what are the reactants and products of the oxidative branch of the HMP shunt
G-6-P -----> CO2 + 2NADPH + ribulose-5-P
95
what enzyme catalyzes the rate limiting step of the oxidative branch of the HMP shunt
G-6-P dehydrogenase
96
what are the reactants and products of the nonoxidative branch of the HMP shunt
ribulose-5-P ------> ribose-5-P + G3P and F6P
97
explain the respiratory burst (steps)
within the phagolysosome of (neutrophils and monocytes) NADPH reduces oxygen; superoxide dismutase then converts radical oxygen to hydrogen peroxide; which gets combined with chloride to generate HOCl radical (hyperchlorite aka bleach) or gets shunted over to the HMP shunt to regenerate more NADPH
98
what is the purpose of respiratory burst
rapid release of ROS for immune response
99
what defect causes chronic granulomatous disease
NADPH oxidase deficiency
100
why are patients with chronic granulomatous disease at increased risk for infection by catalse positive species (i.e. S. aureus and aspergillus)
patients with CGD can use the hydrogen peroxide produced by pathogens (since they can't generate their own), but when pathogens invade that can neutralize their own H2O2 (using catalase) there is no H2O2 for the patient's immune system to utilize against infection
101
what molecule allows P. aeruginosa to kill competing microbes
pyocyanin
102
when lactoferrin is secreted how does it inhibit microbial growth
iron chelation
103
explain why NADPH is important
generates glutathione used by RBCs and other cells to detoxify free radicals
104
what are the two main categories of triggers for NADPH deficiency patients
drugs (i.e. sulfa drugs, primaquine, antimycobacterials, fava beans)infection (immune response triggers free radical release)
105
what is the inheritance of GDPD deficiency
X-linked
106
what benefit does G6PD deficiency confer
increased malaria resistance
107
what is seen on histology for G6PD deficiency
Heinz bodies (oxidized hemoglobin)Bite cells (partially consumed cells that escaped splenic macrophage destruction)
108
what defect causes essential fructosuria
defect in fructokinase
109
what is the inheritance of essential fructosuria
autosomal recessive
110
what are the symptoms of essential fructosuria like
essential fructosuria is a benign condition; generally asymptomaticalthough, fructose appears in the blood and urine
111
are defects in fructose or galactose metabolism more injurious
galactose metabolism(fructose metabolism defects are fairly benign)
112
what defect causes fructose intolerance
hereditary deficiency of aldolase B
113
what is the inheritance pattern of fructose intolerance
autosomal recessive
114
what causes the injurious effects seen in fructose intolerance
F-1-P accumulates leading to a decrease in available phosphate, leading to decreases in glycogenolysis and gluconeogenesis
115
when do symptoms of fructose intolerance present
after eating fruit, honey, juice (anything with fructose)
116
what will the urine dipstick show in a patient with fructose intolerance
negative result; it only tests for glucose
117
what can you detect in the urine of a patient with fructose intolerance
reducing sugars (test for inborn errors of carbohydrate metabolism)
118
what are the symptoms of fructose intolerance
hypoglycemia, jaundice, cirrhosis, vomitting
119
what is the treatment for fructose intolerance
decrease intake of fructose and sucrose (glucose + fructose)
