Final exam Flashcards
(462 cards)
1
Q
__ __ are the energy currency of the cell
A
phosphorylate nucleotides
2
Q
Nucleotide functions (involving structure and constituents)
A
1) Structural component of an array of enzyme cofactors and metabolic intermediates
2) constituent of DNA and RNA
3
Q
the ability to do what with genetic info is a fundamental condition of life?
A
ability to store and transmit genetic info from one generation to the next
4
Q
the __ __ sequence of protein, and the __ sequence of RNA is specified by a ___ sequence in the cell’s DNA
A
amino acid
nucleotide
nucleotide
5
Q
What is a GENE?
A
segment of DNA molecule containing info required for synthesis of functional bioproduct (either protein or RNA)
6
Q
Only known functions of DNA (2)
A
storage and transmission of biological info
7
Q
RNA - several classes (3)
A
rRNA - components of ribosomes (that carry out protein synthesis)
mRNA - intermediates carrying genetic info from one or more genes to ribosome
tRNA - translate info in mRNA into specific aa sequence
8
Q
Nucleotides have (3) characteristic components:
A
1) Nitrogenous (Nitrogen containing) base
2) pentose sugar (ribose and a deoxyribose)
3) 1 or more phosphates (high E phosphate bond)
9
Q
Nucleoside
A
molecule without phosphate group
glycosylamines consisting of base bound to ribose/deoxyribose sugar via β-glycosidic linkage
10
Q
Nitrogenous bases are ___ of two parent compounds: __ and ___
A
derivatives
pyrimidine and purine
11
Q
the base of a nucleotide is joined covalently at __ of pyrimidines and __ of purines in what type of bond? to what carbon of the pentose? what about phosphate?
A
N1, N9
N-β-glycosyl bond to 1’ C of pentose
phosphate esterified to 5’ C
12
Q
How is the N-β-glycosyl bond formed
A
by removal of H2O
- OH from pentose, and H from base
13
Q
Both DNA and RNA contain (2) major PURINE bases
A
adenine (A) & guanine (G)
14
Q
Both DNA and RNA contain (2) major PYRIMIDINE bases
A
cytosine (C) &
thymine (T) in DNA
uracil (U) in RNA
15
Q
Nucleic acids have (2) kinds of pentoses
A
recurring deoxyribonucleotide units of DNA contain 2’-deoxy-D-ribose
ribonucleotide units of RNA contain D-ribose
16
Q
In nucleotides, both types of pentoses are in what form?
A
β-furanose (closed 5-membered ring containing O)
- ‘puckered’ NOT planar
17
Q
What defines the identity of the nucleic acid?
A
the PENTOSE - regardless of base composition
18
Q
Common Course Themes
A
1) stereochemistry is important
2) limited # of molecules support life processes
3) minor modifications lead to major changes
19
Q
Cells also contain nucleotides with phosphate groups in positions other than…
A
on the 5’ carbon
- cAMP, cGMP
20
Q
___ bonds link successive ___ in nucleic acids
A
phosphodiester
nucleotides
21
Q
successive nucleotides of RNA and DNA are covalently linked through…
A
phosphate group ‘bridges’ in which 5’ phosphate group of one nucleotide unit is joined to 3’-hydroxyl group of next nucleotide creating PHOSPHODIESTER linkage
22
Q
The covalent backbone of nucleic acids consists of alternating…
side group?
A
phosphate and pentose residues
- nitrogenous bases may be regarded as side groups joined to backbone at regular intervals (parallel to axis) NOT PERPENDICULAR
23
Q
backbones of RNA and DNA are hydro___.
A
hydroPHILIC
24
Q
high ENERGY phosphate bond hydrolysis provides …
A
chemical energy to drive many cellular rxns
25
Nucleoside triphosphates most commonly used for chemical E by hydrolysis
ADENOSINE 5'-triphosphate (ATP)
| also UTP, GTP, CTP
26
How does ATP synthesis play an important thermodynamic role in biosynthesis?
When coupled to rxn with + free energy change, ATP hydrolysis shifts equilibrium of overall process making it spontaneous (product formation favoured)
27
Coenzymes containing adenosine
```
coenzyme A (CoA)- functions in acyl group transfer rxns
NAD+ - functions in hydride transfer
FAD functions in electron transfer
```
28
Adenosine is central to the __ cycle
TCA (citric acid cycle)
29
Adenosine and redox reactions
NAD+ - functions in hydride transfer
| FAD
30
Some nucleotides are regulatory molecules
cAMP, ppGpp, cGMP
31
Cells respond to environment by taking cues from __ or other external chemical signals
hormones
32
the interaction of these extracellular chemical signals (___ messengers) with receptors on the cell surface often leads to production of ___ ___ inside the cell.
first
| secondary messengers
33
the production of these secondary messengers inside cell leads to...
adaptive changes in the cell interior
34
Often, the 2nd messenger is a ?
| most commonly...?
nucleotide!
| cAMP (adenosine 3',5'-cyclic monophosphate)
35
cAMP is formed from __ in a reaction...
ATP
| reaction catalyzed by adenyl cyclase, an enzyme associated with inner face of plasma membrane
36
cAMP is a common second messenger produced...
in response to hormones and other chemical signals
37
chromatid
sister pairs of genetic info
38
Histones mostly made from ___
arg and lys
39
chromosomes are wrapped around ___
| __-___ base pairs per chromosome
histones
| 48-240
40
how many of each chromosome per cell?`
2 - one maternal, one paternal
41
___ bond/linkages join one nucleotide to another from the .... to a ___ attached to the ....?
phosphodiester
5' ribose oxygen to a phosphate attached to the 3' oxygen
(5'-3' phosphodiester oxygen)
42
A string of bases is made __ --> __
| and it is read ___--> ___
5' --> 3'
| 3' --> 5'
43
centromere
focal point of 2 sister chromatids
44
telomere
cap - prevent main code from breaking down
45
3' end corresponds to the..
| 5' end corresponds to the...
hydroxyl group
phosphoryl group
in both DNA and RNA
46
purine and pyrimidine bases are hydro___
hydroPHOBIC and relatively insoluble in water at near neutral pH of cell
47
one of two important modes of interactions between bases in nucleic acids are...
hydrophobic stacking interactions in which two or more bases are positioned with planes parallel
48
the stacking also involves combination of...between bases
van der waals and dipole-dipole interactions between bases..
49
Base stacking helps to minimize ...
| interactions are very important in ...
contact of bases with water
| stabilizing 3D structure of nucleic acids
50
the most important mode of interaction between two (occasionally 3 and 4) complementary strands of nucleic acids are?
hydrogen bonds involing amino and carbonyl groups
51
base pairs interact through?
H bonds
A=T G≡C A=U
3 bw G & C, 2 bw A & T/U
52
nucleic acids are ___ of nucleotides
polymers
53
1) 5' end
| 2) 3' end
1) lacks nucleotide at 5' position
| 2) lacks nucleotide at 3' position
54
In deoxyribonucleotides, OH group on 2' carbon is replaced with..
H (in DNA) not in RNA
55
sequence of nucleic acids is always written from ...
5' (left) to 3' end (right)
56
B-DNA exists commonly as a
right-handed α helix
| 3.4A/base
57
structure of DNA
hydrophillic backbone faces out with bases on inside
| 10 residues per turn
58
DNA strands are ...
antiparallel DNA fits model best (complementary)
59
Antiparallel DNA strands fit model best because?
provides ability for better bonding in limited space
60
DNA structural stabilization (2)
1) electrostatic interactions: (-) charged phosphate groups on outer surface where they can be neutralized by a) histones, b) cations (Mg2+) c) polyamines
2) base interactions
a) H bonds b/w bases (dipole-dipole interactions)
b) stacking interactions b/w planes of adjacent base pairs (van der waals & dipole-dipole, pi stacking)
61
a new strand of DNA is always synthesized in the ____ direction
5'-->3'
62
strand serving as template is read from __ end toward __ end
3' end --> 5' end
63
because both strands are synthesized in the 5'-->3' direction...
one strand is synthesized in short pieces called okazaki fragments
64
leading strand
continuous strand - the one in which 5' --> 3' synthesis proceeds in the same direction as replication fork movement
65
lagging strand
discontinuous strand - the one in which 5' --> 3' sythesis proceeds in direction opposite to direction of fork movement
66
To duplicate DNA strands, what is needed?
1) replication enzyme (DNA polymerase) - only functions in one direction
2) all 4 dNTP's (dATP, dGTP, dTTP, dCTP)
3) Mg2+
4) DNA template
5) primer (usually RNA, not DNA, synthesized by primase) with free 3' OH to be extended by enzyme
67
Catalysis by virtually all DNA polymerase prominently involves ?
two Mg2+ ions at the active site
68
two central requirements for DNA polymerization
1) template
| 2) primer
69
significance of a primer for DNA polymerase?
strand segment (complementary to template) with free 3' OH group to which nucleotide can be added because DNA polymerase can only add nucleotides to preexisting strand
70
How do okazaki fragments become a continuous strand?
joined together by a ligase
71
(3) distinct phases of transcription - conversion of DNA sequence to RNA
1) initiation
2) elongation
3) termination
72
Transcription - 1) initiation
RNA polymerase recognizes a promoter site (specific sequence) of DNA prior to the gene and DNA is unwound to create template
73
Transcription - 2) Elongation
Polymerase moves along gene synthesizing a complementary copy of DNA template but now using ribonucleoside triphosphate as precursors
74
Transcription - 3) Termination
When polymerase encounters a termination sequence it releases RNA and dissociates from DNA to end transcription
75
The Genetic Code
set of rules that determine how mRNA is translated into an amino acid sequence, where sequence is read as triplets called codons.
76
Each codon specifies an…except?
amino acid except UAG, UGA, UAA (stop codons)
77
UAG does not always act to signal that protein is complete...
instead it can reprogrammed to act as genetic blueprint for 22nd amino acid, pyrrolysine
78
___ which codes for ___ also serves as an initiation codon.
AUG, methionine
79
3 important themes? of DNA synthesis
1) complementary strands - make transfer possible
2) DNA synthesis - similar to protein synthesis
3) DNA has markers - start and stop, in b/w - amino acids
80
Genetic info passed on using same mechanism as ?
RNA to protein
81
In eukaryotes, mRNA is transported to ___ to become associated with ___ (__ and __)
cytosol
| ribosome (rRNA and protein)
82
Translation
formation of proteins from mRNA code (read in 5' to 3' direction) by ribosome
83
Translation - stage 1
Amino acid activation - AA covalently bound to its corresponding tRNA
84
Translation - stage 2
Initiation - mRNA-ribosome complex is formed and 1st aminoacyl-tRNA (initiator tRNA) binds to 1st codon
85
Translation - stage 3
Elongation - other codons are read sequentially by ribosome that associates w/ appropriate aminoacyl tRNA and polypeptide sequence grows from N to C terminus as amide bonds are formed
86
Translation - stage 4
Termination - when ribosome encounters stop codon, it releases polypeptide and ceases protein synthesis
87
Translation - stage 5
Folding and post translational processing - protein must fold properly to be active and may/may not be modified by enzymes (portions cleaved off or substituents added)
88
Genetic code is degenerate...
>1 codon per amino acid
89
What is an aminoacyl tRNA?
amino acids covalently bound to tRNA
90
fats and oils used as stored forms of energy in living organisms are derivatives of ___ ___.
fatty acids
91
Biological function of lipids (9)
1) storage of energy
2) insulation
3) water repellant
4) buoyancy control & acoustics in marine mammals
5) membrane structure
6) cofactors for enzymes
7) signalling molecules
8) pigments
9) antioxidants
92
Lipids 1) storage of energy (2)
reduced compounds - lots of available energy
| hydrophobic - good packing
93
Lipids 2) insulation from environment (3)
low thermal conductivity
high heat capacity (can absorb heat)
mechanical protection (can absorb shocks)
94
Lipids 3) water repellant (2)
hydrophobic nature - keep surfaces dry
| prevents loss of h2o via evaporation
95
Lipids 5) membrane structure (1)
main structure of cell membranes
96
Lipids 6) cofactors for enzymes (2)
vitamin K: blood clot formation
| coenzyme Q: ATP synthesis in mitochondria
97
Lipids 7) signalling molecules
paracrine hormones
steroid hormones
growth factors
vitamin A and D
98
Lipids 8) pigments
colour of tomatoes, carrots, pumpkin
99
Lipids 9) antioxidants
vitamin E
100
Fatty acids are ...
carboxylic acids with hydrocarbon chains containing b/w 4 to 36
101
Lipids
organic molecules characterized by low solubility in water (relatively hydrophobic)
102
Lipids that do not contain fatty acids
cholestral, terpenes...
103
lipids that contain fatty acids
complex lipids
104
lipids that contain fatty acids can be further separated into (2)
storage and membrane lipids
105
almost all natural FA's have an __ # of C's and most are ___
even
| unbranched
106
Saturated FA's
no double bonds b/w carbons in chain
107
Monounsaturated FA's
one double bond b/w carbons in alkyl chain
108
Polyunsaturated FA's
more than one double bond in alkyl chain
109
Omega-3 FA's are ___ ___ but can't be…?
essential nutrient
| synthesized by humans (but we need them)
110
Why is an alternate nomenclature used for PUFA's
physiological role of PUFA's is related more to position of double bond near methyl end of chain (rather than carboxyl end)
111
Which PUFA's are called omega-3 fatty acids
PUFA's with a double bond b/w C-3 and C-4 when using the most distant c from carboxyl group (omega) as # 1 C.
112
Which omega-3 PUFA can synthesize (2) other omega-3 PUFAS?
| What are they?
ALA
| EPA DHA
113
Physical properties of FAs and compounds that contain the are largely determined by (2)
length and degree of unsaturation of hydrocarbon chain
114
Solubility and FA's
decreases as chain length increases
115
Melting Point and FA's
decreases as chain length decreases
| decreases as # of double bonds increases
116
Saturated chains of FA's - conformation?
extended
117
Natural unsaturated FA's - configuration?
double bonds are commonly in cis, kinks chain
118
Saturated FA's - packing/favorable interactions
pack in fairly orderly way
| extensive favorable interactions
119
Unsaturated CIS FA's - packing/favorable interactions
pack less orderly due to kink
| less extensive favorable interactions
120
Why do unsaturated cis FA's have lower MP?
takes less thermal energy to disrupt disordered packing of unsaturated FA's
121
State at room temp:
a) unsaturated
b) saturated
a) oily, liquid
| b) solid, waxy consistency
122
Trans fats are formed by?
partial dehydrogenation of unsaturated FA's - cis to trans configuration
123
why are trans fats made?
to increase shelf life or stability at high T of oils used in cooking
124
what is the advantage of trans double bonds?
allows a given FA to adopt extended conformation, can pack more regularly, show higher MP than cis forms
125
Trans fat are double trouble for your health because?
raise your bad (LDL) cholesterol
and lowers good (HDL) cholesterol
increases risk of heart disease
126
Majority of FA's in biological system are found in form of ___.
triacylglycerols (triglycerides)
127
triacylglycerols
3 FA's esterified to the 3 OH groups of glycerol
128
(2) advantages of using triacylglycerols as stored fuel rather than psychs (glycogen and starch)
1) C atoms of FAs are more reduced than those of sugars and oxidation yields much than 2x as much energy
2) hydrophobic, therefore unhydrated - don't have to carry extra weight of water of hydration associated with stored psachs
129
primary storage form of lipids?
body fat - triacylglycerols (non polar)
130
a) solid lipids
| b) liquide lipids
a) fats
| b) oils
131
triacylglycerols are less soluble in water than FAs due to?
lack of charged carboxylate group
132
density of fats vs water
less dense therefore they float
133
Short term energy needs ?
glucose & glycogen - quick delivery
134
long term energy needs?
fats - good storage, slow delivery
135
Waxes
esters of long chain saturated and unsaturated FAs with long chain alcohols
136
Waxes - solubility and MP
insoluble
| high MP - higher than triacylglycerols
137
Waxes - functions (5)
1) storage of metabolic fuel (plankton)
2) protection/pliability of hair and skin
3) waterproofing for birds feathers
4) protection from evaporation in plants
5) used in lotions, ointments, polishes
138
Beeswax is mixture of?
large # of lipids, including esters of triacontanol, & long chain alkane hentiacontane
139
Structural Lipids in Membranes - Membrane lipids are?
amphipathic - hydrophobic (non polar tail) and hydrophilic (polar head group) parts - usually attached to FA
this directs packing into sheets called membrane bilayers
140
Diversification can come from:
1) modifying of different backbone
2) changing FA's
3) modifying head groups
141
properties of head groups determine?
surface properties of membranes
142
different ___ and ___ have different membrane lipid head group compositions
organisms and tissues
143
Glycerophospholipids
one type of membrane lipid
hydrophobic regions are composed of 2 FAs joined to glycerol
primary constituent of cell membranes
144
Glycerophospholipids - 2 __ __ form __ linkages with 1st and 2nd OH groups of _-___-_-____
fatty acids
ester
L-glycerol-3-phosphate
145
Glycerophospholipids - head group at physiological pH?
CHARGED
146
General structure of Glycerophospholipids
2 fatty acids attached in ester linkages to 1st and 2nd C
unsaturated FA's commonly found connected to C2
head group (substituent group) attached through phosphodiester linkage to 3rd C
- polar alcohol in head group
147
Phosphatidylcholine
major component of most eukaryotic cells membranes
| many prokaryotes including E coli can't synthesize this lipid, their membranes don't contain this
148
Phosphatidylcholine transportation?
transported b/w membranes w/ in cell by phosphatidylcholine transfer protein (PCTP) -
149
Phosphatidylcholine plays a role in?
plays role in membrane-mediated cell signalling and PCTP activation of other enzymes
150
Ether lipids
one of the 2 acyl chains is attached to glycerol in EITHER (vs ester) linkages
151
Plasmalogens
```
ether linked (where most glycerophospholipids have ester linked FA) alkyl chain (contains double bond b/w C1 and C2)
(vinyl ether analog of phosphatidylethanolamine)
```
152
Ether Lipids - platelets-activating factor
aliphatic ether analog of phosphatidylcholine
| acetic acid has esterified C2
153
platelets-activating factor - function/role
molecular signal
stimulates aggregation of blood platelets
plays role in mediation of inflammation
154
Sphingolipids
| backbone and substituents , head group
type of membrane lipid
backbone=long chain amino alcohol SPHINGOSINE
FA joined to backbone via amide linkage
polar head group connected to sphingosine by glycosidic or phosphodiester linkage
155
the sugar containing glycosphingolipids are found largely in?
outer face of plasma membrane
156
Sphingomyelin
```
subclass of sphingolipids
- ceramide + phosphocholine attached to alcohol
```
157
ceramide
sphingosine + amide linked FA
158
Sphingomyelin is abundant in ?
myelin sheath that surrounds some nerve cells in animals
159
Sphingomyelin vs Phosphatidycholine
structurally similar
160
Blood groups are partly determined by?
type of sugars located on head groups in glycosphingolipids
161
the structure of the sugar on head groups in glycosphingolipids is determined by?
an expression of specific glycosyltransferases
162
Individuals with…will have O antigen
no active glycosyltransferase
163
Individuals with…will have A blood group
glycosyltransferase that transfers N-acetylgalactosamine group
164
Individuals with…will have B blood group
glycosyltransferase that transfers galactose group
165
Defects in the turnover of __ __ leads to a ...
```
membrane lipids
# of diseases
partial breakdown products accumulate in tissues (causing disease)
```
166
Sterols
structural lipids in membranes of most eukaryotic cells
167
Sterol structure
almost planar, rigid steroid nucleus consisting of 4 fused rings
(3 with 6 C's, one with 5)
168
Cholesterol
major sterol in animal tissues, amphipathic
polar head group (hydroxyl) in A-ring
various non polar side chains
169
Cholesterol and related sterols are present where?
in membranes of most eukaryotic cells.
170
Cholesterol and related sterols function? (2)
1) modulate fluidity & permeability
| 2) thicken plasma membrane
171
How do mammals obtain cholesterol? (2)
from food, or synthesize it de novo in liver
172
How can lipids (cholesterol) be moved from tissue or origin to where they will be consumed/stored if they are insoluble in water?
carried in blood plasma bound to proteins - via blood vessels
(plasma lipoproteins)
173
Cholesterol in low-density lipoproteins
tends to deposit and clog arteries
174
many ___ are derivatives of sterols
hormones
175
Steroids
oxidized derivatives of sterols
176
Steroid structure (compared to cholesterol)
Steroids have the sterol nucleus, but lack alkyl
chain found in cholesterol
177
the difference in Steroids structure compared to cholesterol results in?
steroids are more polar than cholesterol
178
Steroid hormones are synthesized how?
Steroid hormones are synthesized from cholesterol in gonads and adrenal glands
179
How are they are carried through the body?
in the bloodstream, usually attached to carrier protein
180
Many of the steroid hormones are?
male and female sex hormones
181
Testosterone
male sex hormone - produced in testes
182
Estradiol
one of the female sex hormones - produced in ovaries and placenta
183
Cortisol and Aldosterone
hormones synthesized in cortex of adrenal gland
| regulates glucose metabolism and salt excretion
184
Prednisone & Prednisolone
synthesized steroids used as anti-inflammatory agents
185
Brassinolide
growth regulator found in vascular plants
186
Function of Steroid hormones
| transportation, function, produces?
move through bloodstream (on protein carriers) from site of production to target tissues, where they enter cells, bind to highly specific receptor proteins in nucleus and trigger changes in gene expression & thus metabolism
187
Prednisone & Prednisolone are mediated in part by?
inhibition of arachidonate release by phospholipase A2 and consequent inhibition of synthesis of leukotrienes, prostaglandins & thromboxanes.
188
Biologically active lipids are present in what amounts?
relatively smaller amounts than storage or structural lipids
189
Biologically active lipids play vital roles as?
signalling molecules between nearby cells
190
Lipid soluble vitamins?
A, D, E, K
191
Arachidonic acid (omega-6 FA) derivates as ___ ___
signalling lipids
192
Arachidonic acid is the precursor of?
Eicosanoids
193
3 classes of Eicosanoids
prostaglandins
thromboxanes
leukotrienes
194
what are Eicosanoids?
paracrine hormones - substances that act only on cells near point of hormone synthesis
195
what are Paracrine hormones?
substances that act only on cells near point of hormone synthesis (rather than transported in blood to act on cells in other tissues/organs)
196
Prostaglandins purpose?
inflammation, fever
197
Enzymatic oxidation of arachidonic acid yields?
family of biologically active lipid products
198
Eicosanoids storage?
not stored within cells, but are synthesized as required
199
How eicosanoids are synthesized?
starts with signal that causes reaction in cell membrane
- arachidonic acid freed from membrane phospolipids by specific enzyme (phospholipase A2) , signal leads to specific response
200
for inflammatory purposes, arachadonic acid is generated by?
action of a secretory lipase
201
for signalling purposes, arachadonic acid is mobilized by?
specific lipase
202
what converts FA to prostaglandins, prostacyclin, thromboxanes, and leukotrienes?
cyclooxygenase, peroxidase, lipooxygenase
203
Eicosanoid Hormones are produced when needed from?
arachidonic acid via phospholipase A2
204
Eicosanoids play a role in?
inflammation, smooth muscle contraction, platelet function
205
Thromboxanes purpose
formation of blood clots
206
Leukotrienes purpose
smooth muscle contraction in lungs
207
how does Vitamin D regulates calcium uptake?
vitamin D3 is not itself biologically active but it is converted by enzymes in liver and kidney to calcitriol, a hormone that regulates calcium uptake in intestine & calcium levels in kidney and bone
208
Vitamin A (aka?) functions as? precursor for?
retinol
functions as hormone and as visual pigment
precursor for other hormones involved in signalling
209
Vitamin E, K, and lipid quinones are?
antioxidants - destroy most reactive forms of oxygen radicals and other free radicals protecting unsaturated FA from oxidation & preventing oxidative damage to membrane lipids
210
Polyketides
diverse group of biologically active lipids with medicinal uses
secondary metabolites - not central to metabolism but serve some subsidiary function
211
Summary:
a) Triacylglycerols
b) phospholipids
c) sphingolipids
d) cholesterol
a) main storage lipid
b) man constituent of membranes
c) play role in cell recognition
d) both membrane lipid & precursor for steroid hormones
212
The lipid bilayer is ___
| Saturated fats create what kind of environment?
dynamic
| rigid environment, a non fluid environment
213
the rigid, non fluid environment of the lipid bilayer sets stage for cholesterol how? affects membrane./?
hydrophobic ring packs in with the saturated fatty acids, reduces membrane fluidity and permeability.
214
__ is in lipid bilayer, with ___ attached
phosphatidylcholine
215
phosphatidylcholine - PUFAs attached are the … for?
substrate pool for secondary messengers
216
Cholesterol
| Alkyl side chain - role?
Structural -
| non polar - functions to embed cholesterol in membrane
217
Modification of steroid nucleus results in?
an incredible variety of biologically active lipids
218
what % of Cholesterol is synthesized endogenously?
synthesized in body - 75%
219
Risk factor of CHD? (coronary heart disease)
LDL cholesterol
220
How are cholesterol levels targeted?
Drugs - statin drugs
221
How do Statin drugs work?
reduce synthesis, resins to increase excretion from body and absorption inhibitors
222
what is needed to make eicosanoids?
PUFA with unsaturated bond pattern to support folding into active form
223
Steroid hormone are synthesize where? release into what? taken up by what?
specialized cells, released into blood vasc. system, taken up by target tissue
224
(2) modes of action for steroids
1) slow action
| 2) fast acions
225
Slow action Hormones involves?
involves binding to target tissue, retrieval of genetic material & new protein synthesis.
hormone action is due to protein expression .
226
Example of slow action hormone
Testosterone binds to androgen receptor sites resulting in gene transcription
227
Fast action Hormones involves?
involves membrane associated receptors activating intracellular signalling cascades (non-genomic actions)
228
Glucocorticoids support a variety of which functions? producing?
cardiovascular, metaboilc, immunologic, homeostatic
| producing both slow and fast action effects
229
Hormones grouped into by receptor binding (5)
1) androgens
2) glucocorticoids
3) estrogens
4) mineralcorticoids
5) progestogens
230
non-steroidal anti-inflammatory agents do what?
| example?
inhibit enzymes (aspirin)
PUFA is not converted to active biomolecule
- reduces inflammation & pain
- blood clotting in heart attack
231
Vitamins
Organic nutrients required in small amounts, perform a variety of functions.
- cannot be synthesized, required in diet
232
(2) general classes of vitamins
1) water soluble
| 2) fat soluble (soluble in non polar organic solvents)
233
Folic acid acts as a carrier on ?
one carbon units.
234
Lipid soluble vitamins are ___ and are absorbed with ….. and overcome.. by?
hydrophobic
| other dietary fats and overcome transport problems by associating with proteins
235
Vitamin D is not strictly a vitamin since...
it can be synthesized from cholesterol products in the skin.
236
Major source of Vitamin D ?
Endogenous synthesis
237
Vitamin D levels in excess of those required for mineral homeostasis reduce the risk of? (4)
insulin resistance, obesity and metabolic syndrome associated w/ obesity, various cancers.
238
How does Vitamin D act as a hormone?
converted into active form (by enzymes): calcitrol which binds to nuclear receptor
239
Synthesis of active form of Vitamin D (calcitrol) is regulated by?
factors that respond to Ca and phosphate in blood
240
Calcitrol works in concert with? to do what?
| regulate..balance..affects..
Calcitrol works in concert with Parathyroid hormone in Ca2+ homeostasis, regulation in blood, balance b/w deposition/mobilization from bone
241
Calcitrol acts through nuclear receptors to?
activate synthesis of intestinal absorption of Ca, increases renal excretion of Ca, and mobilizes bone mineral content
242
Calcitrol affects transcription of?
affects transcription of genes that regulate Ca
243
Vitamin D - summary of its roles
maintenance of Ca balance, enhance intestinal absorption, mobilization of bone minerals, gene expression regulation and cell differentiation
244
Vitamin D deficiency can cause (3)
rickets - bones of young kids fail to mineralize
osteomalacia - demineralization of bones
osteoperosis - fracture in older women
245
Low levels of Vit. D are associated with? (5)
1) ^ mortality
2) multiple sclerosis
3) gestational diabetes, preeclampsia, small infants
4) some cancers
5) ^ risk of viral infections
246
Vitamin A - Primary Deficiency
| occurs due to?
to low consumption of provitamin (carotenoids) from fruits & veggies or preformed vitamin A from animal & dairy products.
247
Vitamin A - Secondary deficiency
| associated with?
associated with chronic malabsorption of lipids, impaired bile production and release, and chronic
exposure to oxidants, such as cigarette smoke, and chronic alcoholism.
248
Retinoid hormones
| derived from?
ß-carotene --> vitamin A1 (retinol) --> retinoid acid
249
retinoid receptors in cells?
all cells have at least one form of retinoid receptor
250
similarity between RETINOIC ACID and thyroid hormone, the steroid hormones and Vitamin D? (hint: binding)
retinoic acid binds to nuclear receptors that bind to response elements in the DNA and regulate the transcription of certain genes.
251
Retinoid hormones are most active in?
cells experiencing rapid growth
252
Vitamin A1 Function (2)
- maintains?
- important to?
1) Maintains healthy skin and mucus membranes (through gene expression)
2) important to development of bones&teeth
253
Vitamin A1
may help?
may relieve?
help treatment of rough, dry skin, acne, boils psoriasis and other skin disorders (Retinoic acid)
- May relieve night blindness, eye inflammation, unhealthy hair, dandruff, peeling nails, frequent colds & bronchial complaints
254
ß-carotene significance (conversion)
pro vitamin widely found in nature
| can be converted to vit. A1 (retinol) which is converted to the visual pigment 11-cis-retinal
255
(2) paths of function for 11-cis-retinal
| hormonal and non-hormonal
ß-carotene -> retinol -> visual pigment 11-cis-retinal
can be converted into retinoid acid (hormone) or visible light causes conformational cis to trans change in protein (non hormonal function)
256
Vision
| what focuses light? onto what?
lens focuses light on retina
257
Retina is composed of?
layer of neurons
258
Rods vs Cones
Rods- night vision, high resolution
| Cones - colour vision
259
Rods and cones function? (form links with..)
| how does signal get to brain
form synapse (links) with several ranks of interconnecting neurons that convey and ganglion cells integrate signals - send resulting signal through optic nerve to visual cortex of brain
260
how does Visual transduction occur?
1) rhodopsin formed by…
2) light causes?
1) 11-cis-retinal combines with opsin protein to form rhodopsin (has 7 transmembrane helices embedded.
2) light hits chromophore resulting in cis to trans change (11-cis-retinal to 11-trans-retinal)
(this bond change alters protein structure)
261
After change in structure of chromophore causing conformational change in rhodopsin molecule...
rhodopsin interacts w/ G protein TRANSDUCIN and this protein sends signal
(signal amplification)
262
How is there a significant signal amplification with one change of Rhodopsin?
One Rhodopsin change results in five hundred Transducin changes.
263
toxicity (from vitamins?) is just an..
over expression of normal functioning
264
Excessive Vitamin A leads to?
nauseau, anorexia, hair loss, blurry vision, vomiting, muscle/abdominal pain, weakness/drowsiness
265
Chronic cases of excessive Vitamin A?
hair loss, dry skin, insomnia, weight loss, anemia, bone fractures on top of other symptoms
266
Isotretinoin, a vitamin A derivative commonly used to treat acne, can produce?
symptoms associated with excess Vitamin A
| headache, blurred vision, confusion, associated w/ increased intracerebral pressure
267
Symptoms from Isotretinoin begin to resolve when?
when intake of the offending substance is stopped
268
Chronic intake of preformed vitamin A may be associated with? why?
osteoporosis & hip fractures
| because it suppresses bone building while simultaneously stimulating bone breakdown
269
Vitamin E is also known as the?
Sex Vitamin
270
functions attributed to Vitamin E (5)
1) antioxidant function
2) enzymatic activités
3) gene expression
4) neurological function(s)
5) MOST IMPORTANT - suggested to be in cell signalling)
271
1) the most important function of vitamin E has been suggested to be in?
2) It may not have a significant role in?
1) in cell signaling
| 2) antioxidant metabolism
272
How do antioxidants work?
aromatic ring of tocopherols (biological antioxidants) reacts w/ & destroys oxygen & free radicals protecting unsaturated fats from oxidation and preventing oxidative damage to membrane lipids (can cause cell fragility)
273
Membranes Go Rancid:
| Lipid Peroxidation refers to the ?
Oxidative degradation of lipids
274
Oxidative degradation of lipids is when…
| it affects?
when free radicals take electrons from the lipids in cell membranes, resulting in cell damage
- affects PUFAs
275
Lipid per oxidation:
| oxidative degradation of lipids affects polyunsaturated fatty acids because?
PUFA contain multiple double bonds in b/w which lie methylene bridges (-CH2-) that possess especially reactive H’s
276
When radicals react w/ non-radical.. what happens?
| what descriptive mechanistic name does this lead to?
another radical is produced leading to descriptive mechanistic name "chain reaction mechanism”
277
When does the radical reaction stop?
when two radicals react and produce a non-radical species
| TERMINATION step
278
Initiation step of Radical Reaction
FA radical produced
Notable initiators in living cells are reactive oxygen species (ROS), such as OH- and Hydroperoxyl (HO2), which combines with hydrogen atom to make water and fatty acid radical.
ROS + H --> H2O + FA radical
279
How are Membranes protected by antioxidants?
There are significant levels of Vitamin E in membranes, serum & liver stores.
- oxidized before PUFAs - terminates rxn
280
Where are significant levels of Vitamin E found?
membranes, serum and liver stores
281
Many polyketides find use in medicines (3)
Erthryomycin: antibiotic
Amphotericin B: antifungal
Lovastatin: inhibitors of cholesterol synthesis
282
Erythromycin
- function
- mechanism
(binds to? inhibits synthesis of.. which processes?)
Inhibits growth of bacteria.
Mechanism not fully understood.
Binds to 50s subunit of bacterial 70s rRNA complex, protein synthesis & subsequent structure & function processes critical for life or replication are inhibited.
283
Amphotericin B
| how does it cause fungal cell death?
Binds w/ ergosterol (component of fungal cell membranes) forming transmembrane channel that leads to ion (K+, Na+, H+ and Cl-) leakage & fungal cell death.
284
Lovastatin
member of what drug class?
used for? in combo with what?
statin drug class,
used in combo with diet, weight-loss,& exercise for lowering cholesterol (hypolipidemic agent) in those with hypercholesterolemia to reduce risk of CHD.
285
```
Vitamin D
1) synthesis
2) functions as?
works with?
targets?
```
1) endogenous synthesis possible
2) steroid hormone
parathyroid hormone
liver, kidney, bone
286
Vitamin A
a) synthesis?
b) functions?
a) required preformed in diet
| b) chromophore, steroid hormone
287
Vitamin A's relation to Vit D
Hormone-receptor complex regulates genes governing cell growth and differentiation
288
Vitamin E
a) synthesis?
b) functions?
a) required preformed in diet
| b) antioxidant
289
What reaction consumes Vitamin E?
reaction with ROC
290
Absence of Vitamin A, D, & E create?
deficiency symptoms
291
Excess Vitamin A, D, & E create?
toxicity
292
Amino acid precursor of Niacin
tryptophan
293
Pellegra
vitamin deficiency disease caused by deficiency of Niacin or tryptophan
294
Pellegra
| defined in southern USA: caused by? (3)
maze, meat, molasses (which are low in vitamins)
295
Pellegra
| the 3 "M" causes? (4)
1) dermatitis (inflammation of skin)
2) dementia
3) diarrhea
4) death
296
This indigenous process made more niacin available
corn soaked in an alkaline solution
297
Pellagra is common in what countries/continents? (4)
Africa, Indonesia, North Korea and China
298
Scurvy is caused by?
Vitamin C deficiency
299
Water Soluble Vitamins (4)
1) pantothenic acid (CoA)
2) thiamine (TPP)
3) niacin (NAD+)
4) riboflavin (FAD)
300
1. Pantothenic Acid:
TCA Cycle and FA Synthesis.
301
2. Thiamine:
Multi-enzyme reactions of CHO metabolism. Pentose phosphate pathway.
302
3. Niacin:
Electron carriers oxidation/reduction reactions
303
4. Riboflavin:
Electron carriers oxidation/reduction reactions
304
A variety of enzyme cofactors serving many of chemical functions are unrelated structurally except for the presence of ___ (included as part of their structure)
adenosine
305
the water soluble vitamins are all involved in?
cellular energy production
306
(3) stages of cellular respiration
| STAGE 1
Oxidation of fatty acids, carbohydrates and some amino acids yield acetyl-CoA.
307
(3) stages of cellular respiration
| STAGE 2
Oxidation of acetyl-CoA in the citric acid cycle yields four steps in which electrons are captured.
308
(3) stages of cellular respiration
| STAGE 3
Electrons are funneled into mitochondria enzyme chain and the electrons from NADH and FADH2 are turned into useful energy.
The final acceptor of electrons is oxygen.
309
Energy released in Stage 2 of Cellular respiration in the Citric Acid cycle is conserved in?
in the reduced electron carriers NADH and FADH2
310
(3) stages of cellular respiration
1) Acetyl-CoA production
2) Acetyl-CoA oxidation
3) Electron-transfer + oxidative phosphorylation
311
TPP is coenzyme form of ?
vitamin B1 (Thiamine)
312
Stage 1 - Simple explanation
taking all of the energy yielding compounds and breaking them down to common fuel
electrons captured and moved to e-transport chain - ATP
313
Stage 2 - simple explanation
common tool box
| take in 1 substrate + release energy (electrons) moved to e-transport chain - ATP
314
Stage 3 - simple explanation
mitochondria enzyme chain is tool box
| electrons (energy) carried by metabolic energy carriers (NADH & FADH2) and turned into useful energy - ATP
315
the final acceptor of electrons is?
oxygen
316
TPP - function
| a) metabolic
Central role in metabolism of carbohydrates (i.e. oxidative decarboxylations)
- metabolism of branched chain aa's
Transketolase reaction of PPP (links CHO and lipid metabolism).
317
TPP - function
| b) neural
```
Thiamine pyrophosphate (TPP) functions in nerve transmission
- phosphorylates, & activates chloride channels in nerve membranes
```
318
TPP deficiency
Peripheral neuritis, beriberi, heart failure and edema.
319
TPP is involved in?
enzyme complex, (coenzyme of pyruvate decarboxylase and dehydrogenase)
320
Coenzyme A- role in:
| metabolism
Central role in acyl group metabolism- links CoA to TCA, fatty acid oxidation, cholesterol synthesis and acylation reactions
321
Coenzyme A: deficiency
Wide spread in nature. No deficiencies observed.
322
because of Thiamine's ring structure...
it can be broken down (fragile vitamin)
323
Niacin - metabolic role
Coenzyme role in energy production.
| Source of ADP-ribose for ribosylation of proteins and nucleoproteins involved in DNA repair.
324
Niacin - neural role
NAD products act to increase intracellular calcium in response to neurotransmitters and hormones.
325
Niacin - deficiency
Pellagra – dermatitis, dementia and diarrhea
326
RIboflavin - metabolic role
Coenzyme in mitochondrial respiratory chain (STAGE 3), key enzymes in fatty acid, amino acid oxidation(STAGE 1) and the citric acid cycle(STAGE 2).
Flavin hyperperoxides generates superoxide and perhydroxyl radicals (oxidant stress in the body).
327
Riboflavin deficiency characterized by?
| Fatal?
cheilosis (inflamed mouth), desquamation (peeling skin) and inflammation of the tongue, and a seborrhoea dermatitis (inflammatory skin disorder).
Non fatal
328
De novo synthesis refers to?
the synthesis of complex molecules from simple molecules
329
Vitamin B12, also known as?
cobalamin
330
Vitamin works with? to provide? for what?
works with folate to provide one carbon residues for DNA synthesis
331
What serves as a sensitive measure of vitamin status and why?
Red blood cells because they turn over rapidly.
332
Vitamin B12 deficiency causes? leads to?
pernicious anemia, leads to megaloblastic anemia.
333
What happens if there is a deficiency of these water soluble vitamins?
no useful energy at cellular level
334
What happens if there is no useful energy at cellular level?
no ATP no catabolic rxns to feed anabolic rxns
335
Metabolic consequence and target/vulnerable tissue if deficiency of water soluble vitamins?
rapidly turning over (synthesized) tissue - in trouble
336
Anemia is caused by either (2)
1. level of red blood cells below normal (cofactor for DNA synthesis) - megaloblastic anemia
2. level of hemoglobin below normal
Results in fatigue – not enough O2 to tissues
337
Without Vitamin B12, what doesn't function?
Folic Acid
338
Vitamin B12 is involved in...
Folic acid metabolism, Folate can't release methyl groups
339
which (2) things are needed for 1 carbon metabolism
vitamin B12 and folic acid
340
(4) things that happen if vitamin B12 deficiency: FOLATE TRAP
1) folate can't release methyl groups
2) S-adenosyl-methionine a primary methyl donor is not formed
3) Methylation of DNA, proteins and lipids stops
4) Nucleoside biosynthesis stops. B12 deficiency targets rapidly growing tissue.
341
The FOLATE TRAP is a second demonstration of the…
| It shows them as..
water soluble vitamins working in concert.
key cofactors in intermediary metabolism.
342
B Complex Vitamins
(6)
```
Vitamin B1 (thiamine) TPP
Vitamin B2 (riboflavin)
Vitamin B3 (niacin)
Vitamin B5 (pantothenic acid)
Vitamin B9 (folic acid)
Vitamin B12 (cobalamin)
```
343
Thiamin, Niacin and Riboflavin act as?
enzymatic cofactors
344
– Pantothenic acid acts as an?
an acyl carrier group
345
Thiamin, Niacin, Riboflavin and Pantothenic acid all work together in?
Pyruvate Dehydrogenase Reaction
346
Vitamin C
what is it?
serves to?
a water soluble antioxidant
| - serves to protect Vitamin E from oxidation
347
Hormones
what are they?
production, transportation, function?
small molecules or proteins produced in one tissue, released into circulation, carried to other tissues where they act through receptors to bring about changes in cellular activities
348
In neuronal signalling...
nerve cells release neurotransmitters that act on nearby cells
– Distance may be small (~μm)
349
In hormonal signaling...
hormones are carried by the bloodstream to nearby cells or other organs
– Distance may be great (1 m or more)
350
Basics of endocrine signalling (4)
coordination of metabolism of whole organism
role of specific tissue & organs
hormonal regulation of fuel metabolism
control of body mass
351
Neuroendocrine System
metabolic fine control/integration.
352
Neuronal signaling - how it occurs
Electrical signals originate in the cell body, travel to the axon tip, where neurotransmitters are released and diffuse to target cells.
353
Hormonal signaling - how it occurs
Hormones are secreted into the blood- stream, which carries then throughout the body to target tissues.
354
In Neuronal and Hormonal signaling -
| commonality?
Both neurotransmitters and hormones interact with specific receptors on or in their target cells, triggering responses
355
Individual cells in one tissue sense a change in organisms circumstance, and respond by?
secreting chemical messengers that pass to another cell in same or different tissue where messenger binds to receptor molecule and triggers change in second cell
356
Hormones act through….
Specific high-affinity interactions
357
Receptors in different cells
different sets of receptors - defines range of its hormone responsiveness
358
each cell type has its own combo of hormone receptors which defines range of its hormone responsiveness
2 cell types with same receptor may have different intracellular targets of hormone action and thus respond different to same hormone
359
Different cell types with same receptor
may have different intracellular targets of hormone action and thus respond DIFFERENT to same hormone
360
Even structurally similar hormones can...
bind different receptors
| can have diff effects if they preferentially bind to diff receptors
361
Interactions are high-affinity so?
only low amounts of hormone are needed
362
Specificity of hormone action results from...
structural complementarity b/w hormone and its receptor
363
response of the same hormone in different tissues with same receptor may be..
DIFFERENT
364
Cell surface receptors
peptide of amine hormone binds to receptor on outside of cell
acts through receptor w/o entering cell
- produces second messenger
- causing altered activity of preexisting enzyme
365
Nuclear receptor
steroid of thyroid hormone enters cell
hormone-receptor complex acts in nucleus
- altered transcription of specific genes
altered amount of newly synthesized proteins
366
Epinephrine binds to receptors that ...
spans a membrane.
367
• Signal amplification – starts with ...
the hormone
368
Binding of epinephrine causes what to happen?
Binding induces conformational change that produces a second messenger
369
Signal amplification results when enzyme associated with a __ __ is activated and...
signal receptor is activated and catalyzes activation of many molecules of 2nd enzyme each of whig activates many molecules of a 3rd enzyme
370
Binding of epinephrine causes conformational change which causes a cascade of reactions…
RESULT?
FAST ACTING hormone
activates (through its receptor) adenyl cyclase - produces many cAMP which activate protein kinase A which activates glycogen phosphorylase b kinase which activates glycogen phosphorylase b
RESULT is signal amplification
- 1 epinephrine causes production of MANY glucose-1-phosphate from glycogen
371
Nuclear Receptor Hormones
steroid, retinoid, vitamin D, thryoid hormones are non polar & pass through plasma membrane to nucleus where they bind to a receptor in nucleus
372
After binding of hormone to nuclear receptor …
| causes?
Receptor-hormone complex binds to DNA, acts as transcription factor
– Increases or decreases expression of target genes
373
How long does process of expression of target genes (decreased/increased) by hormones binding to nuclear receptor take?
hours to days
374
Vitamin D involved in…
| decreased levels of Ca ...
calcium binding
signal indicates increase of Ca into body which increases synthesis of active form of Vit D - intestine - de novo synthesis of Ca binding - increases Ca into GI tract
375
Classes of Mammalian Hormones (3)
1) Paracrine
2) Endocrine
3) Autocrine
376
Paracrine
released into extracellular space, diffuse to neighboring target
377
Example of Paracrine Hormones
Eicosanoids
378
Endocrine
released to blood, carried to target cells
379
Example of Endocrine hormone
insulin, glucagon
380
Autocrine
affect the cell where they’re produced (but bind to surface receptors)
381
Classification of Mammalian Hormones based on
path from release to target
382
Blood sugar levels outside the normal range may be an indicator of?
of a medical condition
383
Persistently high levels of blood glucose referred to as
Hyperglycemia
384
Persistantly low levels of blood glucose referred to as
Hypoglycemia
385
Hyperglycemia
Persistently high levels of blood glucose
386
Hypoglycemia
Persistantly low levels of blood glucose
387
Diabetes mellitus is characterized by?
persistent hyperglycemia from any of several causes, and is the most prominent disease related to failure of blood sugar regulation
(either because pancreas does not produce enough insulin, or b/c cells do not respond to insulin that is produced)
388
Adult Onset Diabetes Epidemic
- % of diabetes cases
- # diagnosed cases worldwide
90% of diabetes cases are type 2
| 300 million diagnosed cases world-wide
& growing
389
Adult Onset Diabetes Epidemic
| hallmark is?
resistance to insulin
390
In Adult Onset Diabetes Epidemic,
| the body's initial response is?
to make more insulin
391
In Adult Onset Diabetes Epidemic,
| over time, some individuals have to..
supplement with insulin
392
Diabetes and Metabolic Syndrome
| affects what % of adult US popn?
27%
393
Diabetes and Metabolic Syndrome
| Cluster of symptoms along with insulin resistance (5)
1) abdominal obesity
2) high triglycerides (TAGs)
3) low HDL
3) high BP
4) elevated blood glucose (may not full-blown diabetic)
5) often includes other signs of inflammation
394
Physiological Effects of Low Blood Glucose in Humans
1) slightly low (50-60)
2) 30-40
3) 0- 20
1) subtle neurological signs (hunger, sweating, trembling, release of epinephrine/glucagon/cortisol
2) lethargy, convulsions, coma
3) permanent brain death (if prolonged)
4) death
395
Normal range of blood glucose
60-90 mg/100 mL
396
Fuel use over time
1) immediately after meal
2) 2 or more hours after meal
3) 4 hours after
1) increase of glucose
2) blood glucose begins to drop, FA use increases
3) increased TAG hydrolysis increase FA available fuel for muscle liver
397
post-prandial
after meal
398
Immediately after meal, glucose levels increase so...
Insulin stimulates glycolysis and glycogen synthesis
399
2 or more hours after meal, blood glucose begins to drop and FA use increases so...
Glucagon secreted, liver glycogen releases glucose
400
Four hours post-prandial, increased TAG hydrolysis increases ?
FA available fuel for muscle and liver
401
Response to prolonged fasting…
| to provide glucose for brain (2)
liver deaminates or transaiminates amino acids
- in liver, carbon skeletons of glucogenic aa are converted to pyruvate, then glucose via gluconeogenesis
to provide glucose for brain
402
Response to prolonged fasting…
| adipose (FAT) tissue releases?
FA which are oxidized to acetyl-CoA in liver, but oxaloacetate depleted (by citric acid cycle) to make glucose so forms ketone bodies which are exported from liver to heart, skeletal muscle and brain (which use these as fuels instead of glucose)
403
All of these responses of the body are in response to?
(liver de/transaminating aa's, c skeletons of glycogenic aa -> pyruvate -> glucose
FA -> acetyl CoA but oxaloacetate depleted so -> ketone bodies - exported to other tissues)
Lack of carbohydrates leads to these effects
404
Specialized pancreatic cells secrete important hormones
Pancreatic ß Cells secrete insulin in response to changes in blood glucose
405
Adrenal Medulla
Part of Adrenal gland that releases epinephrine which results in glucose mobilization
406
Pancreas - response to
a) low levels of blood glucose
b) high levels of blood glucose
a) Glucagon released
| b) Insulin released (decreased glucagon release)
407
Glucagon and Insulin are both...
Peptide hormones
408
```
Epinephrine vs. Glucagon
1) similarity
2) differences
a.
b.
```
1) Epinephrine stimulates same cAMP cascades as glucagon in fat & liver
BUT ALSO...
2)
a. Stimulates glucagon secretion itself & inhibits insulin secretion
b. Breaks down MUSCLE glycogen as well as liver glycogen
409
Effects of Glucagon on Blood Glucose (6) production&release of glucose by liver
breakdown, synthesis, 3 conversions, mobilization
a) ↑ glycogen breakdown (liver)
b) ↓ glycogen synthesis (liver)
c) ↓ glycolysis (liver) (converts glucose to pyruvate)
d) ↑ gluconeogenesis (liver)
e) ↑ FA mobilization (adipose tissue)
f) ↑ ketogenesis
410
Glycolysis
conversion of glucose to pyruvate
411
Gluconeogenesis
generation of glucose from non-carbohydrate carbon substrates
412
Effects of Glucagon on Blood Glucose
a) ↑ glycogen breakdown (liver)
b) ↓ glycogen synthesis (liver)
c) ↓ glycolysis (liver) (converts glucose to pyruvate)
d) ↑ gluconeogenesis (liver)
e) FA mobilization (adipose tissue)
f) ↑ ketogenesis
a) glycogen --> glucose
b) less glucose stored as glycogen
c) less glucose used as fuel in liver
d) aa's, glycerol, oxaloacetate -> glucose
e) less glucose used as fuel by liver & muscle
f) provides alternative to glucose as energy source for brain
413
ketogenesis
process by which ketone bodies are produced as a result of fatty acid breakdown.
414
Effects of insulin on Blood Glucose: Uptake of glucose by cells and storage as triacylglycerides & glycogen (7)
uptake(2), synthesis(3), breakdown(1) conversion/production(1)
a) ↑ glucose uptake (muscle, adipose)
b) ↑ glucose uptake (liver)
c) ↑ glycogen synthesis (liver muscle)
d) ↓ glycogen breakdown (liver muscle)
e) ↑ glycolysis, acetyl-CoA production
f) ↑ FA synthesis (liver)
g) ↑ Triacylglycerol synthesis (adipose tissue)
415
Effect of Insulin favours (2) things
conversion of excess glucose to 2 storage forms:
a) glycogen (in liver & musclle)
b) triacylglycerides (in adipose tissue)
416
Physiological Effects of Epinephrine: Prep for Action
| 3
↑ heart rate
↑ BP
↑ dilation of respiratory passages
417
Physiological Effects of Epinephrine:
↑ heart rate
↑ BP
↑ dilation of respiratory passages
OVERALL EFFECT?
↑ delivery of O2 to tissues (muscle)
418
Metabolic Effects of Epinephrine: Prep for Action
| 7
a) ↑ glycogen breakdown (muscle,liver)
b) ↓ glycogen synthesis (muscle, liver)
c) ↑ gluconeogenesis (liver)
d) ↑ glycolysis (muscle)
e) ↑ FA mobilization (adipose tissue)
f) ↑ glucagon secretion
g) ↓ insulin secretion
419
OVERALL EFFECT of metabolic effects of EPINEPHRINE:
a) ↑ glycogen breakdown (muscle,liver)
b) ↓ glycogen synthesis (muscle, liver)
c) ↑ gluconeogenesis (liver)
d) ↑ glycolysis (muscle)
e) ↑ FA mobilization (adipose tissue)
f) ↑ glucagon secretion
g) ↓ insulin secretion
a/b/c: ↑ production of glucose for fuel
d) ↑ ATP production in muscle
e) ↑ availability of FA as fuel
f/g: reinforce metabolic effects of epinephrine
420
Peptide Hormones - Origin
Synthesized on ribosome of β-cells as preproinsulin (larger precursor of insulin) and stored in secretory vesicles in β-cells
421
Peptide Hormone synthesis requires...
functioning pancreas
422
Insulin is secreted in response to (what situation)?
increased blood glucose levels (meal situation)
423
Targets of Insulin the Peptide Hormone
| Binds to? in where? (4)
Many
| Binds to receptors in muscle, brain, liver, adipose tissue, and other fuel-metabolizing tissues
424
In order for Insulin to bind..
Functioning receptors are required
425
Peptide Hormone Insulin - Response
Stimulates glucose uptake in muscle & fat
Glucose → glucose 6-phosphate
• In liver: insulin stimulates glycogen synthase, inactivates glycogen phosphorylase (which turns glycogen to glucose)
– Glucose 6-phosphate → glycogen
426
Insulin stimulates conversion of excess glucose to ...
FAT
427
Also in liver, INSULIN stimulates which (2) processes?
Glycolysis: glucose-6-phosphate → Acetyl-CoA
TAG synthesis: Acetyl-CoA → TAG (exported by VLDL)
428
In FAT, Insulin stimulates...
TAG synthesis
429
Energy allows for ...
de novo tissue synthesis
430
Adipocytes (aka?)
what are they?
what are they specialized in?
(AKA lipocytes and fat cells
| - the cells that primarily compose adipose tissue, specialized in storing energy as fat
431
ADIPOCYTES are metabolically active in that they...
carry out glycolysis (glucose→ pyruvate)
convert Acetyl-CoA to FAs
use FAs to make TAGs
release FA when other tissues need them
432
ADIPOCYTES use FA to make TAGs from (2)
from intestinal lipids via chylomicrons
from liver via VLDL
433
ADIPOCYTES
carry out..
covert..
Glycolysis: glucose→ pyruvate
Acetyl-CoA→ FA → TAG
release FA when needed by other tissues
434
ADIPOCYTES release FA when...
other tissues (skeletal muscle, heart) need them
435
As we gain weight .. body composition?
the % of lean body mass decreases as fat accumulates.
436
When Demand for FUEL RISES:
| Hormones work quickly on adipocytes...
lipases (in adipocytes) hydrolyze TAGs to release FAs
| - release is accelerated by epinephrine
437
How is release of FAs by hydrolysis of TAGs by lipases accelerated?
Epinephrine stimulates cAMP dependant phospohorylation of perilipin and thus gives hormone-sensitive lipase access to lipid droplet
438
Insulin's affect on HSL
counterbalances effect of epinephrine, & decreases activity of HSL
439
Adipocytes: In individual with healthy body mass...
TAG uptake in diet = TAG oxidation for energy
440
Adipocytes: In overweight individuals...
excess calorie intake results in enlarged adipocytes, unable to store more
441
Pro-inflammatory state of ADIPOCYTES
- secrete… which attracts…
which infiltrates.. producing… causing..
release…enter… accumulation.. causing?
enlarged adipocytes secrete MCP-1 attracting macrophages which infiltrate adipose tissue, produce TNFα triggering lipid breakdown + FA release into blood (export)
when FA enter muscle cells, they accumulate in small lipid droplets
This ectopic storage of lipids somehow causes insulin resistance
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Adult Onset Diabetes Treatments - LIFESTYLE
| (2) things to do (3) things
Diet and exercise:
1) to ↓ obesity
2) manage blood glucose
3) ↑ insulin sensitivity of muscles
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Adult Onset Diabetes Treatments - HORMONAL TREATMENTS
| under what circumstances?
Insulin, if endogenous insulin secretion is inadequate
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Adult Onset Diabetes Treatments - HORMONAL TREATMENTS
| under what circumstances?
Insulin, if endogenous insulin secretion is inadequate
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Adult Onset Diabetes Treatments - DRUGS
AMPK activator: Metformin (glucophage)
PPAR activators
Sulfonylureas
Dipeptidyl protease-4 inhibitors (Januvia)
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Adult Onset Diabetes Treatments - DRUGS
AMPK activator: Metformin (glucophage)
PPAR activators
Sulfonylureas
Dipeptidyl protease-4 inhibitors (Januvia)
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AMPK activator: Metformin (glucophage)
mimics effects of ADIPONECTIN- protein involved in regulating glucose levels as well as FA breakdown.
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AMPK activator: Metformin (glucophage)
mimics effects of ADIPONECTIN- protein involved in regulating glucose levels as well as FA breakdown.
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PPAR activator: THIOZIDINEDIONES
↑ adiponectin
| stimulate adipocyte differentiation, thereby ↑ capacity for TAG storage
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PPAR activator: THIOZIDINEDIONES
↑ adiponectin
| stimulate adipocyte differentiation, thereby ↑ capacity for TAG storage
447
Sulfonylureas
bind to ATP-gated K+ channel in ß cells stimulating insulin release (close channels)
447
Sulfonylureas
bind to ATP-gated K+ channel in ß cells stimulating insulin release (close channels)
448
DPP IV - Dipeptidyl protease-4 inhibitors (Januvia)
prevent proteolytic degradation of glucagon-like peptide-1 (GLP-1) - peptide hormone producedin gut that stimulates pancreatic insulin secretion
- prolongs action of GLP-1, effectively ↑ insulin secretion
448
DPP IV - Dipeptidyl protease-4 inhibitors (Januvia)
prevent proteolytic degradation of glucagon-like peptide-1 (GLP-1) - peptide hormone producedin gut that stimulates pancreatic insulin secretion
- prolongs action of GLP-1, effectively ↑ insulin secretion
449
NEUROENDOCRINE SYSTEM
NS controls production of specific hormones via this system
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NEUROENDOCRINE SYSTEM
NS controls production of specific hormones via this system
450
Blood glucose levels are controlled by?
by peptide hormones: insulin and
glucagon. (Epinephrine is also part of the control system)
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Blood glucose levels are controlled by?
by peptide hormones: insulin and
glucagon. (Epinephrine is also part of the control system)
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What (2) things can leads to diabetes?
Defective insulin production by pancreas
or
Inadequate insulin sensing by target cells
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What (2) things can leads to diabetes?
Defective insulin production by pancreas
or
Inadequate insulin sensing by target cells
452
How can Adult onset diabetes be treated?
by lifestyle changes and drugs
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How can Adult onset diabetes be treated?
by lifestyle changes and drugs
