Metabolism Flashcards
1
Q
2 major hormones that dictate metabolism
A
insulin
glucagon
2
Q
Fed State
A
energy storage state of metabolism
response to eating
glucose stored in glycogen & fat
3
Q
Function of the liver in Fed State of metabolism
A
produces glycogen
converts glycogen to fat
4
Q
Amino acids function in metabolism Fed State
A
protein synthesis OR fat production
5
Q
Where is glycogen stored?
A
Liver
Skeletal muscle
6
Q
Where is fat stored?
A
adipose tissue
7
Q
Adipose tissue (S)
A
dense | large energy source
glucose–>fat storage
8
Q
What is the building block for fat storage in adipose tissue?
A
triglycerides
9
Q
Basal State
A
between meals | maintains BG
down glucose –> down insulin, up glucagon
breakdown fat/glycogen
10
Q
What occurs in the liver during the basal state?
A
Breaks down glycogen into glucose and exports it into blood
=maintain BG & ship to brain
Also makes glucose to maintain BG
11
Q
What does adipose tissue do in the basal state?
A
uses fat storage and transports to blood for energy for skeletal muscle & tissues
12
Q
Starved State
A
no food intake | increase ketosis to maintain BG
GREATER decrease glucose –>
down insulin | up glucagon
depleted glycogen, ketone production increase (glucose-sparing effect)
13
Q
What happens to the liver do in the starved state?
A
glycogen depleted
14
Q
What happens with gluconeogenesis in the starved state?
A
turned on = glucose made from fat storage
15
Q
Glucose Sparing Effect
A
ketones used by the brain which keep animal alive in starved state
16
Q
Enzyme function
A
dictate metabolic pathways
17
Q
Active site
A
where enzyme binds to substrate (where rxn occurs)
18
Q
Cofactors
A
not part of protein
inorganic compound
19
Q
Function of cofactors
A
provide functional groups and help w/ electron transfer
20
Q
Coenzymes
A
non-protein, contains vitamins
21
Q
Coenzyme function
A
provide functional groups
22
Q
Km
A
enzyme’s affinity for substrate
23
Q
Catabolic Pathway
A
break down energy
24
Q
Anabolic Pathway
A
build things (small –> big molecules)
25
Purpose of Catabolic Pathways
generate ATP
transfer electrons
26
Ways to regulate enzymes
Inhibition
Activation
Phosphorylation
27
Inhibition
antagonist
stops reaction
28
Types of Inhibition
irreversible
reversible
29
Irreversible Inhibition
completely stop enzyme
ex: toxins, drugs (COX inhibition)
30
Reversible Inhibition
can turn on/off
31
Types of Reversible Inhibition
competitive
non-competitive
32
Competitive Inhibition
compete for binding site & blocks product from being made
*can be overcome by increasing substrate*
33
Non-competitive Inhibition
bind to separate site on enzyme and inhibit by conformational change
34
What is most common way to regulate metabolism?
Non-competitive inhibition
35
Activation (type of enzyme regulation)
agonist
allosteric (non-competitive)
36
Allosteric (type of activation)
binds to different site on enzyme --> conformational change
= speeds up enzyme or decrease Km
37
Phosphorylation
adding phosphate group activates or inhibits it
38
Kinase
phosphorylates a protein
39
Phosphatase
dephosphorylates a protein
40
Gleevec
competitive inhibitor
treats CML & GIST
inhibits repro of oncogene --> decrease tumor growth
41
3 Types of Pathway Regulation
1. Product Inhibition
2. Feedback Inhibition
3. Feed-forward regulation
42
Product Inhibition
product inhibits further production of it
43
Feedback Inhibition
product inhibits enzyme earlier on | takes different pathway
44
Feed-forward Regulation
production --> more production
45
Dry Beri-Beri
neurological
thiamine-deficient diet --> decrease PDH (pyruvate dehydrogenase) --> down ATP
46
Wet Beri-Beri
cardiac
thiamine buildup --> heart failure
47
Thiamine
coenzyme for vitamin for PDH
48
Polioencephalomalacia
disease in cattle
high grain diet increase thiaminase bacteria in rumen
--> anorexia, lethargy, "star-gazers", pressing
49
TCA Cycle Purpose
starting point for carb/fat/protein oxidation
transfer electrons --> ATP in ETC
50
Location of TCA Cycle
Mitochondrial matrix
51
TCA cycle substrate
Acetyl CoA
52
TCA cycle products
Primary: NADH + H+
Secondary: FADH2 + GTP
53
TCA regulatory enzyme
dehydrogenases:
IDH | a-KGDH | MDH
54
How is TCA turned on?
high energy demand (down ATP, up ADP)
ETC activates causes down NADH = TCA ON
55
What turns off TCA?
Low energy demand (up ATP, down ADP)
ETC slows, NADH rises, dehydrogenases inhibited = TCA OFF
56
ETC purpose
generate ATP from oxidizing carbs/fats/proteins
57
ETC Substrate
NADH + H+, FADH2
58
ETC Product
ATP, H2O
59
ETC reg enzyme
ATP synthase
60
What turns on ETC?
high energy demand (down ATP, up ADP)
NADH + H+ donate electrons
61
Location of ETC
inner mitochondrial matrix
(Impermeable membrane)
62
Complex II: Succinate Dehydrogenase
complex in ETC
binds FAD (from TCA cycle)
skips "pumping", produces ATP but LESS than ATP synthase
63
Pyruvate Dehydrogenase (PDH)
protein complex
Pyruvate --> Acetyl CoA (outside TCA)
converts so it can enter mito matrix
64
What is PDH stimulated by?
Ca2+ | ADP | insulin
dephosphorylation activates
65
What is PDH inhibited by?
NADH | Acetyl CoA (product)
phosphorylation inactivates
66
What do coenzymes rely on for proper function?
B vitamins (1,2,3,5)
67
Glycolysis substrate
glucose
68
Glycolysis product
pyruvate or lactate
69
Glycolysis reg enzyme
PFK-1
70
Glycolysis purpose in peripheral tissues
break down glucose for energy
71
Glycolysis purpose in liver
glucose --> pyruvate for fat synthesis
72
What turns on glycolysis in peripheral tissues?
energy demand (up AMP, up PFK1)
73
What turns on glycolysis in liver?
up insulin --> up PFK 2 --> active PFK1
74
Glycolysis in liver (substrate/product)
glucose (substrate) -->
pyruvate + acetyl coA (product)
75
Gluconeogenesis subtrate
lactate | glycerol | alanine
76
Gluconeogenesis product
glucose
77
Gluconeogenesis purpose
maintain BG
convert non-glucose precursors into glucose
78
Gluconeogenesis reg enzyme
pyruvate carboxylase
79
What activates gluconeogenesis?
excess Acetyl CoA from B-oxidation
80
Glycogen Synthesis substrate
UDP-glucose
81
Glycogen Synthesis product
glycogen
82
Glycogen Synthesis purpose
store glucose
83
Glycogen Synthesis reg enzyme
glycogen synthase
84
What activates glycogen synthesis?
insulin dephosphorylates glycogen synthase = ON
85
What deactivates glycogen synthesis?
glucagon phosphorylates glycogen synthase = OFF
86
Glycogenolysis substrate
glycogen
87
Glycogenolysis product
glucose-6-phosphate
88
Purpose of Glycogenolysis in peripheral tissues
glycogen --> glucose for glycolysis --> energy!
89
Purpose of glycogenolysis in liver
glycogen --> glucose to export in blood
90
Glycogenolysis reg enzyme
Phosphorylase
91
What turns on glycogenolysis?
glucagon phosphorylates phosphorylates phosphorylase = ON
92
What turns off glycogenolysis?
insulin dephosphorylates phosphorylase = OFF
93
B-oxidation substrate
fatty acids
94
B-oxidation product
Acetyl CoA
95
B-oxidation purpose
oxidize fatty acids --> NADH + H+ --> ATP
96
B-oxidation reg enzyme
CPT-1
97
What turns off B-oxidation?
fatty acid synthesis which increases malonyl coA = OFF
98
Fatty Acid Synthesis substrate
Acetyl CoA --> Malonyl CoA
99
Fatty Acid Synthesis product
palmitate
100
Fatty Acid Synthesis purpose
make fatty acids to store excess glucose
make carbon chain from amino acids as triglycerides in adipose tissue & liver
101
Fatty Acid Synthesis reg enzyme
Acetyl CoA Carboxylase (ACC)
102
What activates FA synthesis?
up BG, up insulin, dephosphorylates ACC = ON
103
What deactivates FA synthesis?
down BG, down insulin, down ACC
down Malonyl CoA = on B-oxidation = OFF
104
Ketone Formation substrate
Acetyl CoA (excess)
105
Ketone Formation product
ketones:
B-hydroxybutyrate
Acetone
Acetate
106
Purpose of Ketone Formation
generate blood-soluble ketones from excess Acetyl CoA when B-oxidation is high
107
Ketone Formation reg enzyme
Acetyl CoA carboxylase (indirectly)
108
What turns on ketone formation
up B-oxidation --> excess Acetyl CoA = ON
109
Hexokinase
enzyme that traps glucose in cell (by converting to glu-6-phosphate)
IMMEDATE trapping!
110
Location of Hexokinase
most tissues
111
Glucokinase
enzyme in glycolysis that traps glucose in cell by converting to glu-6-phosphate
NOT immediate! need high glu levels (like after meal)
112
Glycolysis location
cytosol
113
Shuttle systems
"shuttle" electrons from cytosol to mitochondrial matrix in glycolysis (so it can get into cell)
114
Malate-aspartate shuttle
more efficient shuttle
makes malate which can get electrons into matrix for TCA
115
Glycerol phosphate shuttle
less efficient shuttle
transfers NADH electrons --> glycerol phosphate dehydrogenase to get into mitochondrial matrix
116
Anaerobic Glycolysis
fastest way to generate ATP
rely on endogenous glycogen (in cell)
117
Purpose of Anaerobic Glycolysis
regenerate NAD so glycolysis can continue
118
Ruminant Gluconeogenesis
rumen can break down cellulose-->glucose
breaks down further then remakes it
119
Propionate
major precursor for ruminant gluconeogenesis
major source of glucose
120
Feline Gluconeogenesis
obligate carnivores
can't handle carbs
convert proteins --> amino acids --> glu (via gluconeogenesis)
121
Cori Cycle
integrates glycolysis + gluconeogenesis
liver + lactate --> glucose --> tissues
122
Branching Enzyme
enzyme in glycogen synthesis
clips glucose chain & moves it so new chain can be formed = branching
123
Purpose of glycogen branching
increase SA, quicker process, more soluble
124
Debranching enzyme
enzyme in glycogenolysis
removes branch so further branching
125
Glycogen phosphorylase
releases glucose from free ends
in glycogenolysis
126
What activates glycogen phosphorylase?
phosphorylation of glycogen phosphorylase
127
Glycogen Metabolism in Liver
glucagon binds to G protein
stim phosphorylation of phosphorylase = active
Glu-6-P dephosphorylates --> export in blood
exports for needs of body
128
Glycogen metabolism in muscle
NO glucagon signaling
stimulated by EPI
uses energy via glycolysis for its own
important in muscle endurance
129
Glycogen Storage Disease
can't maintain BG
glucose-6-phosphatase mutation = can't export glucose
130
What type of fatty acids does the body make? (and saturated/unsaturated?)
palmitic acid (16 carbons)
saturated
131
What is the purpose of saturated fatty acids?
all single bonds, store as many electrons as possible
132
Where does fatty acid synthesis occur?
cytoplasm
133
Is fatty acid synthesis reductive or oxidative?
reductive (giving electrons for storage)
134
What causes Type I Diabetes?
135
B cells
cells that produce insulin
136
How do B-cells produce insulin?
glucose influx via GLUT2
glycolysis makes ATP
ATP inhibits K+ sensitive channel
Depolarization of VG Ca2+ channel
Ca2+ triggers exocytosis
B cell vesicles diffuse out insulin
137
What causes insulin receptor to activate?
phosphorylation of receptor
138
Tyrosine Kinase Receptor
insulin receptor
139
Two ways insulin causes glucose uptake into cell
direct
indirect
140
Direct glucose uptake by insulin
glucose taken up via transporters
141
Indirect glucose uptake by insulin
stimulation of glycolysis / glycogen synthesis
(help clear glucose from blood=uptake)
142
What receptor leads to insulin stimulated by glucose uptake directly?
GLUT 4
143
What causes Type 1 Diabetes?
insufficient insulin
low BG b/c not enough insulin
autoimmune B-cell destruction
144
What causes Type 2 Diabetes?
insulin resistance
plenty of insulin
response muted (no glucose uptake)
145
What species is Type I diabetes most common?
dogs
146
What species is Type II diabetes most common?
cats
147
Type I Diabetes Non-Ketotic symptoms
polyuria | polydipsia (drink)
weight loss | cataracts
148
How do B-cells get destroyed in Type I diabetes?
T-cells/macrophage attack B-cells
decrease insulin overtime
149
Ketoacidosis + symptoms
occurs in diabetes w/o treatment
symptoms: depression, anorexia, dehydration, labored breathing, death
150
Ketoacidiosis pathology
vessels constrict in kidneys --> shut down CNS
151
Ketoacidosis treatment
insulin + fluids
152
What is an underlying cause of T2DM?
obesity
153
Mechanism of T2DM
no signal to IRS1 means no GLUT4 vesicle for glucose to come in
154
Ceramides
lipotoxicity ("toxic lipids")
which inhibit receptor signals for glucose uptake
155
Stages of T2DM
early stage
postprandial hyperglycemia
falling insulin
normal to low insulin (late stage)
156
Eary stage T2DM
up insulin, body tries to compensate
"pre-diabetes"
157
Postprandial hyperglycemia stage Type 2
Type 2 progresses
lose more receptors, really up insulin
158
Falling insulin stage Type 2
insulin decreases B cells die
up glucose @ rest (w/o meal)
up gluconeogenesis & glycogenolysis
159
Normal to Low insulin stage Type 2
cannot produce insulin (transition to closer to Type 1)
160
Amyloid
becomes toxic when builds up in B-cells
leads to loss of insulin production
161
What causes B-cell exhaustion?
up free FA & glucose --> ER stress
162
What is different with insulin signaling between dogs & cats?
cats fewer receptors than dogs
obligate carnivores --> don't clear glucose as quickly and have fewer receptors
163
AMP kinase (AMPK)
enzyme on when energy demand is high (up AMP)
target for T2DM treatment in humans (NOT cats!)
