Final Exam Flashcards
(452 cards)
1
Q
What are the 4 lipid classes?
A
- Fatty Acids
- Triacyclglycerols
- Phospholipids
- Cholesterol
2
Q
Fatty acids have no _____ present, meaning they are fully reduced
A
oxygens
3
Q
What are lipids?
A
Fats, they are a group of organic compounds that are insoluble in water but are soluble in organic solvents
4
Q
Fatty acids are _______ molecules
A
amphipathic
5
Q
What are saturated fatty acids?
A
Solid hydrocarbon chains with no double bonds or kinks
6
Q
What are unsaturated fatty acids?
A
Have one or more double bonds that cause kinks in the acid
7
Q
There are 2 different kinds of fatty acid nomenclature: ?
A
- Fatty acid carbon atoms are usually numbered beginning with the carboxyl terminal carbon atom.
Carbon atoms 2 and 3 are also referred to as α and β, respectively. - Fatty acids can also be numbered from the methyl carbon atom, which is called the omega (ω) carbon.
8
Q
How is the normal nomenclature structured?
A
E.g. 18:1Δ^9
18 = number of carbons
1 = number of double bonds
9 = double bond location
9
Q
Fatty acids, a major source of energy, are stored as triacyclglycerols in what kind of tissue?
A
Adipose
10
Q
Fatty acids are connected to glycerol by an _____ bond
A
ester
11
Q
“Free” fatty acids are highly ____, attaching them to glycerol makes them less so
A
toxic
12
Q
What are the 2 sources of triacylglycerol?
A
- From the diet
- Synthesized in the liver from carbohydrates and proteins if absolutely necessary
13
Q
____ are the most highly concentrated form of stored biological energy
A
Triacylglycerol
14
Q
Triacylglycerol is stored in an _____ form
A
anhydrous
15
Q
Triacylglycerol is too _______ to cross biological membranes
A
hydrophobic
16
Q
Triacylglycerol is degraded in the small intestine and resynthesized in ?
A
intestinal cells (enterocytes)
17
Q
____ break down lipids and usually release a fatty acid
A
Lipases
18
Q
Triacylglycerol broken down by lipases and turned into ?
A
Monoacylglycerol and 2 fatty acids
19
Q
What is the importance of Chylomicrons?
A
Fat shuttles, they transport triacylglycerol in the circulation to tissues
20
Q
Fatty acids are stored as triacyclglycerols in _____ ____ in adipose tissue
A
lipid droplets
21
Q
Adipose tissue has a very ___ capacity for triacylglycerol storage
A
high
22
Q
In the ____, glycerol from lipolysis in adipose tissue can be used for gluconeogenesis
A
liver
23
Q
Fatty Acid Oxidation Occurs in the ?
A
Mitochondrial Matrix
24
Q
To be oxidized, fatty acids need to be:
1. ?
2. ?
A
- Activated (bound to CoA)
- Transported (carnitine shuttle)
25
What is the rate-limiting step of fatty acid oxidation?
Fatty acid transport into the mitochondria
26
In an energy surplus the carnitine shuttle is going to have __ activity; but in an energy deficiency the carnitine shuttle is going to have ___ activity
low, high
27
The ____ step of the carnitine shuttle is regulated, and the enzyme of the step is ?
1st, Carnitine acyltransferase I
28
What are the 4 basic steps in the β-Oxidation of saturated fatty acids?
1. Oxidation
2. Hydration
3. Oxidation
4. Cleavage
29
What is the 1st step in the β-Oxidation of saturated fatty acids?
Oxidation via Acyl CoA dehydrogenase. Introduces trans double bond (α-β or C2-C3)
30
What is an Enoyl CoA?
A generic term describing an unsaturated fatty acid bound to CoA
31
What is the 2nd step in the β-Oxidation of saturated fatty acids?
Hydration via Enoyl CoA hydratase
32
What is the 3rd step in the β-Oxidation of saturated fatty acids?
Oxidation via Hydroxyacyl CoA dehydrogenase
33
What is the 4th step in the β-Oxidation of saturated fatty acids?
Thiolysis/cleavage via thiolase. Carbons 1 and 2 of a fatty acid generate each acetyl CoA
34
In the β-Oxidation of saturated fatty acids, two carbon units are sequentially removed from the ____ end of the fatty acid (carbons bound to CoA)
carboxyl
35
Fatty acid oxidation continues until ?
the fatty acid is completely oxidized to acetyl CoA
36
What is the overall NET production of ATP from the oxidation of palmitate (7 cycles)?
106 ATP
37
What is the importance of Enoyl CoA isomerase?
- Moves double bond from C3-4 to C2-3
- Changes double bond from cis to trans and now becomes an intermediate of the pathway
38
? is a unique product of the beta oxidation of odd chain fatty acids
Propionyl Co-A
39
Propionyl Co-A is metabolized by carboxylase to a 4-carbon intermediate that is eventually converted to ?
succinyl Co-A
40
? are an alternative to glucose as a fuel or energy source
Ketone bodies
41
Ketone bodies are formed by ketogenesis in the _____ only
liver
42
Ketone bodies are utilized by extrahepatic tissues (brain) when [?] is low
glucose
43
Determine which of these ketone bodies are used/not used for fuel:
Acetoacetate: ?
β-hydroxybutyrate: ?
Acetone: ?
Acetoacetate: for fuel
β-hydroxybutyrate: for fuel
Acetone: not for fuel
44
Ketone body formation occurs in the mitochondria of the ___ where acetyl CoA is produced
liver
45
Which ketone body does not contribute to acetyl CoA production?
Acetone
46
Fatty acid biosynthesis occurs in the ____, in the ___ primarily and in adipose
cytosol, liver
47
Fatty acids are synthesized by a multienzyme complex: ?
Fatty Acid Synthase (FAS)
48
In fatty acid biosynthesis, the chain length is increased by sequential addition of ___ -carbon units (derived from acetyl CoA)
2
49
Elongation of fatty acids stops with formation of ______ (C-16)
palmitate
50
Further elongation/desaturation of fatty acids past palmitate is catalyzed by ?
other enzymes
51
What is the primary substrate for fatty acid biosynthesis?
Acetyl CoA
52
_____ is also needed for fatty acid biosynthesis
NADPH
53
? catalyzes the 1st and rate limiting step of FA biosynthesis
Acetyl CoA Carboxylase
54
Palmitate is an ____ of acetyl CoA carboxylase, while Citrate is an _____
inhibitor, activator
55
Glucagon and epinephrine ______ acetyl CoA carboxylase, while insulin ______ it
inactivates, activates
56
What is the 2nd step in Fatty Acid Biosynthesis?
Loading FAS with substrates. Acetyl-CoA to β-ketoacyl synthase via Acetyl transacylase (AT)
57
What is the 3rd step in Fatty Acid Biosynthesis?
Formation of acetyl ACP and malonyl ACP charges/primes. Malonyl CoA to Malonyl ACP via Malonyl transacylase (MT)
58
What is the 4th step in Fatty Acid Biosynthesis?
1st reaction in formation of FA chain, and is a condensation. Activated acetyl and malonyl groups condense forming acetoacetyl ACP. Catalyzed by β-ketoacyl-ACP Synthase
59
What is the 5th step in Fatty Acid Biosynthesis?
Acetoacetyl-ACP (B-ketobutyryl-ACP) is reduced. Reaction a reduction reaction, and is catalyzed by B-ketoacyl-ACP reductase (KR). Electron donor is NADPH.
60
What is the 6th step in Fatty Acid Biosynthesis?
Dehydration. Water is removed from C2 and C3 of β-hydroxybutyryl-ACP to introduce a double bond. Product is trans-Δ2-butenoyl-ACP.
61
What is the 7th step in Fatty Acid Biosynthesis?
Reduction. Double bond of trans-Δ2-butenoyl ACP is reduced to form butyryl-ACP by Enoyl-ACP Reductase. NADPH is the electron donor. One pass through fatty acid synthase is complete.
62
What is the 8th step in Fatty Acid Biosynthesis?
Translocase. Transfer of butyryl group from ACP to KS. Catalyzed by Acetyl transacylase (AT). The next cycle can then start
63
What is the 2nd round in Fatty Acid Biosynthesis?
- Malonyl CoA -> Malonyl-ACP is catalyzed by malonyl transacylase (MT)
- Butyryl group is condensed to malonyl ACP
Repeat:
Reduction
Dehydration
Reduction
Translocation
Product = 6 carbon fatty acid
64
In total, __ cycles of condensation and reduction are required to produce palmitate.
7
65
What is the overall reaction for the synthesis or palmitate:
__Acetyl CoA + __ATP + __NADPH -> __Palmitate + __CoA + __ADP + __Pi + __NADP+ + __H2O
8, 7, 14, 1, 8, 7, 7, 14, 6
66
Most fatty acids are ____ than palmitate (18-26C), mono- and ________fatty acids
longer, polyunsaturated
67
Elongation occurs in _______ ______, and 2 carbons are added at a time from malonyl CoA
endoplasmic reticulum
68
Humans cannot introduce double bonds past carbon __
9
69
Desaturation is the introduction of ? and is catalyzed by _______ enzymes
cis double bonds, desaturase
70
Location of double bond is ____ for each desaturase
specific
71
Humans lack Δ__ and Δ__ desaturases, and so must obtain _____and _______ through the diet
12, 15, linoleate, α-linolenate
72
We use linoleate and α-linolenate to make other ?
long polyunsaturated fatty acids
73
Low energy (↓ AMP): is where AMPK is _____ and AMPK phosphorylates ____ (inactive)
active, ACC
74
High energy (🠕 ATP): is where is AMPK _____ and ACC is de-phosphorylated (_____)
inactive, active
75
Acetyl CoA carboxylase activity is ____ by citrate and insulin
increased
76
Acetyl CoA carboxylase activity is _____ by epinephrine, and glucagon
decreased
77
Acetyl CoA carboxylase activity is ______ by palmitate?
decreased
78
Malonyl CoA inhibits ? (carnitine shuttle), and so blocks ?
carnitine acyltransferase I, beta oxidation
79
Cholesterol is synthesized mainly by the ___, the remainder is from the ____
liver, diet
80
What are the 2 functions of cholesterol?
- Structural component of membranes
- Precursor of bile salts, steroid hormones, & vitamin D
81
Where are the 27 carbons in cholesterol from?
Acetyl CoA
82
Cholesterol is the precursor of 5 steroid hormones: ?
1. Cortisol
2. Estradiol
3. Progesterone
4. Testosterone
5. Vitamin D
83
How many reactions are there is the cholesterol biosynthetic pathway?
25
84
What is the rate limiting step in the cholesterol biosynthetic pathway?
HMG-CoA reductase
85
Where does the cholesterol biosynthetic pathway occur?
the cytosol
86
Cholesterol is synthesized in __ stages
4
87
In cholesterol biosynthesis, there is ___ of NADPH required for these reactions and everything in between and most comes from the ___
LOTS, PPP
88
What is stage 1 in cholesterol biosynthesis?
Formation of mevalonate. 3 acetyl CoA are used to form it. Here HMG CoA reductase is found, and is the target of statins.
89
A total of ___ acetyl CoA are used for each molecule of cholesterol formed.
18
90
Excess cholesterol is converted to bile acids which are stored in _____
gallbladder
91
What are the 3 fates of cholesterol?
1. Hepatocyte plasma membrane
2. Bile Acids
3. Exported in LDLs
92
What is an HDL?
High-density lipoprotein. Picks up cholesterol from blood and tissues
93
What is an LDL?
Low-density lipoprotein. Transport cholesterol from liver to tissues
94
Regulation of cholesterol synthesis occurs in __ ways:
1. When cholesterol levels in the cell drop, the transcription of the gene for HMG-CoA reductase is ____; transcription slows when cholesterol levels are ___
2. The rate of translation of HMG-CoA reductase mRNA is inhibited by ____ _____
3. The degradation of HMG-CoA reductase enzyme is _____ by elevated levels of ____ cholesterol
3, stimulated, high, mevalonate metabolites, stimulated, cellular
95
Together the three regulatory processes of cholesterol synthesis can alter the amount of enzyme by over ___-fold!
200
96
↓ [cholesterol]: leads to __ HMG-CoA reductase, LDL receptor and __ synthesis and __ uptake of cholesterol
🠕, 🠕, 🠕
97
🠕 [cholesterol]: leads to __ HMG-CoA reductase, LDL receptor, and __ synthesis and __ uptake
↓, ↓, ↓
98
What is Familial Hypercholesterolemia?
High circulating cholesterol levels, caused by a defective LDL receptor, the cholesterol is not cleared from the blood, causing atherosclerotic plaques
99
In familial hypercholesterolemia, cholesterol levels get so high they form ?
xanthomas (deposits) in the skin
100
Cholesterol provides _____ to membranes
fluidity
101
Fatty acids have 2 fates: 1. and 2.
1. Triacylglycerol as metabolic energy
2. Phospholipid for membranes
102
What are the 3 most common phospholipids?
1. Phosphatidylcholine
2. Phosphatidylethanolamine
3. Phosphatidylserine
103
Triacylglycerol and phospholipids are synthesized from a _____ pathway, what is it called?
common, Kennedy Pathway
104
? is the starting substrate of TG and PL synthesis
Glycerol 3-phosphate
105
In the Kennedy pathway, _______ catalyzes the sequential attachment of fatty acids to glycerol backbone (____bond)
acyltransferase, ester
106
What is the most abundant phospholipid?
Phosphatidylcholine, at 50%
107
Why is there a second pathway for the synthesis of phosphatidylcholine?
To ensure there is an adequate supply
108
Where does the methylation pathway of the synthesis of phosphatidylcholine occur?
The liver
109
What kind of charge do all of the relevant phospholipids have?
positive charge
110
The synthesis of phosphatidylethanolamine occurs by _________ of phosphatidylserine
decarboxylation
111
Eicosanoids are derived from ______, which is part of a phospholipid present in a ?
arachidonate, cell membrane
112
Arachidonate releases by ?
Phospholipase A2
113
Eicosanoids are termed ?
paracrine hormones
114
Eicosanoids are not stored and so are ?
rapidly degraded
115
______ send messages to nearby cells/tissues including the cell in
which it was made
Eicosanoids
116
The signal for PLA2 activation _____ calcium in the cell; this leads to
______ of PLA2 to the plasma membrane, and phosphorylation of PLA2
which ____ it.
elevates, translocation, activates
117
Biological actions of eicosanoids are _____ in ____ organs
diverse, various
118
What are some examples of the biological actions of eicosanoids?
vasodilation, vasoconstriction, platelet aggregation, inhibition of platelet aggregation, contraction of smooth muscle, chemotaxis of leukocytes, release of lysosomal enzymes
119
What are some of the excess production symptoms of eicosanoids?
pain, inflammation, fever, nausea, vomiting
120
Where does Aspirin target in the realm of arachidonates?
Prostaglandin synthase
121
What is the Ubiquitin-proteasome pathway?
For cellular protein turnover. Ubiquitin molecules are linked to a specific lysine. The protein becomes polyubiquitinated, processed into peptides, and the ubiquitin is eventually cleaved and re-utilized
122
What is proteolysis?
The hydrolytic cleavage if proteins by digestive proteinases; these enzymes are secreted into the stomach and small intestine
123
Gastric acidic environment _____ proteins
and thus enhances proteolysis
denatures
124
The K+/H+ Pump in the membrane of specialized
stomach cells pumps ____ into the stomach in
exchange for K+ at the expense of _____ ______;
generates acidic environment and releases ____.
protons, ATP hydrolysis, heat
125
In some individuals, the K+/H+ pump is overactive, or the esophageal sphincter is weak, which results in
?
gastroesophageal reflux disease (GERD)
126
What are some medications used to treat GERD?
Antacids, histamine H2 receptor blockers, and proton pump inhibitors
127
All digestive proteolytic enzymes are secreted from either specialized gastric cells (pepsinogen) or from the
pancreas (others) as ?
inactive zymogens
128
All zymogens are themselves activated by ?
proteolysis
129
Why are proteinases are synthesized and stored as
zymogens?
So that they don’t break down proteins in the cells
where they are made/stored and don’t digest themselves prior to secretion
130
_____ preferentially cleaves peptide bonds between hydrophobic amino acids or aromatic amino acids.
Pepsin
131
______ cleaves peptide bonds following an Arg or Lys
residue
Trypsin
132
______ preferentially cleaves peptide bonds after an aromatic amino acid.
Chymotrypsin
133
______ broader specificity; cuts after amino acids with smaller, hydrophobic side chains such as Gly, Ala,Val
Elastase
134
What are endopeptidases?
When proteolytic enzymes cleave internal peptide bonds in a substrate
135
Proteases eventually self-_____
inactivate
136
The Amino Acids on either side of a peptide bond form a
____ substrate and generally require _____ enzymes
unique, different
137
Bond between arginine and glycine is cleaved by
_____
trypsin
138
Bond between tyrosine and serine is cleaved by
________
chymotrypsin
139
In regards to the specificities of digestive proteolytic enzymes, two groups target either the amino or
carboxy terminal residue of a peptide, these are called _________ or _______ respectively
aminopeptidases, carboxypeptidases
140
What are the 3 fates of the amino group of amino acids?
Transamination (cytosol)
Oxidative deamination (mitochondria)
Urea Cycle (split between the cytosol and mitochondria)
141
In the Transamination Reaction, there is a transfer of amino group to an α-ketoglutarate. What are the donors/acceptor?
Donors: L-amino acids
Acceptor: α-ketoglutarate
142
In the Transamination Reaction, the amino groups get funneled to ?
Glutamate
143
The Transamination reaction is an obligatory step in the degradation of ?
amino acids (except for Lys and Thr)
144
True or False: the transamination reaction is reversible?
True, Keq is ~1
145
What are the enzymes in the transamination reaction?
Enzymes: aminotransferases
Coenzyme: PLP
146
What are the 2 most important aminotransferases?
Aspartate aminotransferase
Alanine aminotransferase
147
Where is aspartate aminotransferase found?
In the liver mitochondrion
148
Where is alanine aminotransferase found?
Muscle cytosol
149
_____ phosphate (an aldehyde) is an a-amino group acceptor; _______ phosphate is an a-keto (ketone) group acceptor
Pyridoxal, pyridoxamine
150
In ______ phosphate, the amino group of incoming α-amino acid forms covalent linkage with aldehyde group, and the α-keto acid leaves
pyridoxal
151
In _______ phosphate, the ketone group of incoming α-keto acid (typically α-ketoglutarate) forms covalent linkage with amino group. Amino group then
displaced again by active site lysine amino group. Glutamate leaves.
pyridoxamine
152
The incoming amino acid amino group displaces the
lysine amino group, in a fully _____ reaction, and
forms an identical _____ of PLP
reversible, aldimine
153
What is aldimine?
A chemical term that defines an imine (C=N group) derived from an aldehyde
154
An aldimine is also called a ?
Schiff base
155
What is the ping-pong nature of the aminotransferase reaction?
In which when the first substrate (amino acid) is bound to the enzyme (via PLP) and reacts (pyridoxamine phosphate), the second substrate (α-ketoglutarate) cannot bind to form second product (L-glutamate) till the first product (α-keto acid) leaves
156
What is the α-keto acid pair to alanine?
pyruvate
157
What is the α-keto acid pair to aspartate?
Oxaloacetate
158
What is the α-keto acid pair to glutamate?
α-ketoglutarate
159
What is an α-keto acid?
Means there is a ketone group adjacent to a carboxylate group
160
Aminotransferases are important markers for ?
liver or heart damage
161
High serum levels of _____ aminotransferase (also called Glutamate Pyruvate Transaminase or GPT) indicative of damage. Same goes for _____ aminotransferase (also called Glutamate Oxaloacetate Transaminase or GOT).
alanine, aspartate
162
Fate of Glutamate in Liver is to be transported to the mitochondria and undergoes oxidative deamination to release ?
ammonia
163
Oxidative deamination of glutamate is done via which enzyme?
Glutamate dehydrogenase
164
Oxidative deamination removes the amino group from glu as ? and is a reversible reaction
NH4
165
What is the coenzyme in oxidative deanimation?
NAD+ or NADP+
166
High concentrations of NH4+ are ?
toxic
167
NH4+ is converted to urea in the ?
liver mitochondria
168
Excess ammonia in non-liver tissues is transported as _____ to the liver
glutamine
169
What is the nontoxic transport form of NH4+?
Glutamine
170
In the liver, NH4+ is released from glutamine by cleavage by which enzyme?
Mitochondrial glutaminase
171
Alanine transports excess ammonia from muscle tissue to ?
liver
172
In muscle, glutamate is formed from ?.
transaminations
173
The glutamate amino group is ultimately transaminated to pyruvate, forming _____. Once in liver, alanine is transaminated to form ______.
alanine, glutamate
174
Alanine carries ______ from muscle to liver
Nitrogen
175
NH4+ is converted to urea in the ?
liver
176
Where does the urea cycle occur?
The liver
177
What are the 3 precursors of urea?
NH4+, CO2, and Aspartate
178
Historically, urine was a valuable diagnostic tool for defects in ?
nitrogen metabolism
179
In the urea cycle, there are __ cytosolic enzymes that exist as a multiprotein complex
3
180
______ and _____ must be transported in and out of the mitochondria respectively during the cycle
Ornithine, citrulline
181
? is a major regulation point but is actually not part of the urea cycle
Carbamoyl Phosphate Synthetase I (CPS I)
182
The formation of carbamoyl phosphate occurs in the ?
mitochondrial matrix
183
What is the enzyme used in the formation of carbamoyl phosphate?
CPS I
184
How is CPS I regulated?
allosterically
185
What is the first key regulatory step in urea cycle?
The formation of carbamoyl phosphate
186
How many ATP molecules are consumed in the formation of carbamoyl phosphate?
2
187
The formation of N-acetylglutamate is done via which enzyme?
N-acetylglutamate synthase
188
What is happening during the formation of N-acetylglutamate?
Amide bond formation between α-amino group of glutamate and activate carbonyl carbon of acetate
189
The formation of N-acetylglutamate is _______ regulated and only occurs in the presence of _____ amino acids in the liver
allosterically, excess
190
The product N-Acetylglutamate is a required allosteric activator of ?
CPS I
191
Citrullene is formed in the ?
Mitochondrion
192
Ornithine is the first cousin of ____, as it has one ____ CH2 group
lysine, fewer
193
What is going on in the formation of citrulline?
An amide bond is formed between ornithine and carbamoyl phosphate
194
What is the important aspect of citrulline?
It can be transported to the cytosol
195
Citrulline is formed via which enzyme?
Ornithine transcarbamoylase
196
Argininosuccinate is formed from citrulline and aspartate via which enzyme?
Argininosuccinate synthetase
197
Argininosuccinate formation occurs in the ?
cytosol
198
In the formation of argininosuccinate, what intermediate is formed?
L-citrulline adenylate
199
The role of aspartate in the formation of argininosuccinate is to ?
ultimately donate the 2nd NH3 group to urea
200
the formation of arginine and fumarate by argininosuccinate is done via which enzyme?
Cytosolic argininosuccinase or argininosuccinate lyase
201
In the formation of arginine, the other product fumarate can be converted to ?
malate
202
The malate formed by the fumarate (made via the formation of arginine) then goes back to the mitochondrion to feed into which cycle?
TCA
203
The malate formed by the fumarate (made via the formation of arginine) can also be converted to ______ and/or ______
oxaloacetate, aspartate
204
Which cycle supplies most of the arginine requirements for adults?
Urea
205
The hydrolysis of arginine is via which enzyme?
Cytosolic arginase
206
In the hydrolysis of arginine, ____ is finally formed and ____ is regenerated
urea, ornithine
207
What is the overall stoichiometry of the urea cycle:
__CO2 + __NH4+ + __ATP + __Aspartate + __H2O -> __Urea + __ADP + __Pi + __AMP + __PPi + __Fumarate
1, 1, 3, 1, 2, 1, 2, 2, 1, 1, 1
208
A single urea cycle enzyme deficiency will result in _______, or elevated NH4+ in the blood, and is incredibly toxic to the ____ system
hyperammonemia, nervous
209
Citrullinema is a result of what deficiency?
Argininosuccinate lyase deficiency
210
Patients with liver cirrhosis cannot process ?
ammonia to urea
211
Urea cycle requires an ____ of amino acids in the liver, is typically very active in ___ protein diets, very active during _____, and the leftover carbon skeletons are shunted to the ? or to ?
excess, high, starvation, TCA cycle, gluconeogenesis
212
Why is the urea cycle active during starvation?
The human body can't utilize carbohydrates as an energy source, so proteins present in the muscles are broken down and hence use amino acids as energy sources. Since there is an enhancement in the amino acid degradation, more urea is produced
213
What is argininemia?
Defective arginase in urea synthesis, and causes mental retardation
214
What is argininosuccinicacidemia?
Defective argininosuccinase in urea synthesis, and causes vomiting and convulsions
215
What is carbamoyl phosphate synthetase 1 deficiency?
Defective carbamoyl phosphate synthetase 1 in urea synthesis, and causes lethargy, convulsions, and early death
216
What is maple syrup urine disease (branched chain ketoaciduria)?
Defective branched-chain α-keto acid dehydrogenase complex in isoleucine, leucine, and valine degradation, and it causes vomiting, convulsions, mental retardation, and early death
217
What is phenylketonuria?
Defective phenylalanine hydroxylase in the conversion of phenylalanine to tyrosine, leads to a phelylalanine buildup in the blood, and causes neonatal vomiting and mental retardation
218
What are the 2 main treatment options for deficiencies in urea cycle enzymes?
Supplemented diet with benzoate and phenylbutyrate
219
How do treatments like benzoate and phenylbutyrate work?
Form enzyme-catalyzed amide linkages with glycine or glutamine α-amino groups. The resultant products, benzoylglycine and phenylacetylglutamine are then excreted in urine. This can help deplete the liver nitrogen pool, eventually lowering the ammonia levels in blood
220
In the liver, free ammonium is produced from
breakdown of Serine and Threonine by ? and ?
serine dehydratase, threonine dehydratase
221
In the liver, the breakdown of Serine gives ____ and ___ and Threonine gives ______ and ____
pyruvate, NH4+, α-ketobutyrate, NH4+
222
In the kidney, ammonia is generated by the metabolism of glutamine by enzymes ? and ?, and is secreted in urine as ?
glutamate dehydrogenase, glutaminase, free ammonium
223
Other sources of ammonia includes amines from the ___, monoamines that serve as ______/__________, and from the catabolism of _____ and _______
diet, hormones, neurotransmitters, purines, pyrimidines
224
The carbon skeletons of all 20 amino acids are broken
down and fed into only seven central metabolites: ?
Pyruvate, oxaloacetate, α-ketoglutarate, succinyl CoA, fumarate, acetyl CoA, acetoacetyl CoA
225
Which of the seven central metabolites are glucogenic, which are ketogenic?
Glucogenic: pyruvate, oxaloacetate, α-ketoglutarate, succinyl CoA, fumarate
Ketogenic: acetyl CoA, acetoacetyl CoA
226
There are only two amino acids that are purely ketogenic: ?
Leucine and lysine
227
What is the difference between glucogenic and ketogenic?
Glucogenic amino acids can be converted into glucose, which can then be used to produce energy. Ketogenic amino acids can be converted into ketone bodies.
228
______ breakdown generates products that are ketogenic and glucogenic: ______ is ketogenic, _____ is glucogenic via gluconeogenesis.
Phenylalanine, acetoacetate, fumarate
229
The liver lacks the branched chain _______, so breakdown occurs in _____, ____, and _____ tissue.
aminotransferase, kidney, brain, adipose
230
_______, ______, ______, and _____ are all converted to glutamate, and then broken down to α-ketoglutarate
Glutamine, proline, arginine, histidine
231
α-ketoglutarate and pyruvate are the most common ways of breaking down your ?
carbon skeletons
232
It is estimated that about __% or 10^11 (100 Billion) kg comes from ?
60, nitrogen-fixing microorganisms
233
Nitrogenase itself is very sensitive to inactivation by ?
O2
234
Both the reductase and nitrogenase are ? proteins
iron-sulfur cluster (Fe-S)
235
The ____ Cofactor is only found in nitrogenase
MoFe
236
Humans have __ Mo-requiring enzymes and all require the pterin Mo Cofactor
4
237
? is a primary control point of nitrogen metabolism
Glutamine synthetase
238
Glutamine Synthetase is present in ____ organisms.
all
239
Glutamine is _____ source of amino groups in many Biosynthetic Reactions
primary
240
Glutamine synthetase is an allosteric _____ (12 identical subunits)
dodecamer
241
Glutamine Synthetase activity is controlled by 8 _____ regulators
allosteric
242
Combined effect of allosteric effectors in glutamine synthetase is more than ____.
additive
243
Covalent modification of Glutamine synthetase by _____ makes the enzyme more responsive to allosteric inhibitors.
adenylation
244
Adenylylation of Glutamine Synthetase occurs on a ____ residue
tyrosine
245
Adenylation of Glutamine Synthetase leads to its _____, and is the ?.
inactivation, regulatory step
246
Glutamine is the major source of the donor amino group in the formation of ?
amides
247
All amino acids are built from intermediates of which 3 pathways?
Glycolysis, TCA cycle, PPP
248
What are the nonessential amino acids for humans?
Alanine, asparagine, aspartate, glutamate, serine
249
What are the two conditionally essential amino acids for humans?
Arginine, glutamine, and tyrosine
250
Why are arginine, glutamine, and tyrosine considered conditionally essential amino acids?
Specific populations who do not synthesize it in adequate amounts, such as new born infants and people with diseased livers who are unable to synthesize cysteine, must obtain one or more of these from their diet
251
In tetrahydrofolate, the two ____ atoms are the sites where the 1 carbon units get attached
nitrogen
252
Can we synthesize tetrahydrofolate?
No
253
What are the terms synonymous with the 1-C unit "methyl"?
N^5, or -CH3
254
What are the terms synonymous with the 1-C unit "methylene"?
N^5N^10, or -CH2-
255
What are the terms synonymous with the 1-C unit "formyl"?
N^10, or -CHO
256
What are the terms synonymous with the 1-C unit "methenyl"?
N^5N^10, or -CH=
257
N^5-formimino-tetrahydrofolate is involved in ______ metabolism
histidine
258
The conversion of tetrahydrofolate to N^5,N^10-methylene-tetrahydrofolate requires the conversion of serine to ?
glycine
259
Methionine synthesis entails the conversion of homocysteine to methionine via what enzyme?
methionine synthase
260
Methionine synthesis also involves the conversion of N^5 methyltetrahydrofolate to ?
Tetrahydrofolate coenzyme B12
261
When you convert serine to glycine, you liberate a group that ends up on ?
tetrahydrofolate
262
S-Adenosylmethionine (SAM) is a ____ donor in many biosynthetic reactions
methyl
263
When S-Adenosylmethionine is used as a methyl donor, the product is ?
S-Adenosylhomocysteine
264
Hydrolysis of S-Adenoyslhomocysteine yields ______ and ______. Homocysteine has __ more CH2 group than cysteine
adenosine, homocysteine, 1
265
? supplies the CH3- group for methionine biosynthesis
N^5-methyltetrahydrofolate
266
Where the adenosine is linked to methionine?
The sulfur atom
267
Methyl group usually transfers to a _____ or
_____ atom
nitrogen, oxygen
268
Valine ____ threonine deaminase, while isoleucine ____ threonine deaminase.
activates, deactivates
269
What is the amino acid precursor of sphingosine?
Serine
270
What is the amino acid precursor of histamine?
histidine
271
What is the amino acid precursor of thyroxine?
Tyrosine
272
What is the amino acid precursor of epinephrine?
Tyrosine
273
What is the amino acid precursor of serotonin?
Tryptophan
274
What is the amino acid precursor of nicotinamide unit of NAD+?
Tryptophan
275
What is the amino acid precursor of 5,6-Dihydroxyindole?
Tryptophan
276
What is the amino acid precursor of L-Dopamine?
Tyrosine
277
What is the amino acid precursor of Gamma-aminobutyric acid (GABA)?
Glutamate
278
What is the amino acid precursor of heme?
Glycine
279
While only 5% of nucleosides absorbed are reutilized for nucleic acid synthesis, 25% of these are used by the rapidly regenerating _____ (specialized intestinal cells).
enterocytes
280
In the intestinal lumen, the conversion of nucleic acids to nucleotides uses which enzyme?
Nuclease enzymes, phosphodiesterases
281
In the intestinal lumen, the conversion of nucleotides to nucleosides uses which enzyme?
Alkaline phosphatase enzymes
282
In the intestinal lumen, the conversion of nucleosides to purines and pyrimidines uses which enzyme?
Nucleosidase enzymes
283
For the base Adenine, what is the corresponding:
1. Ribonucleoside
2. Ribonucleotide
3. Deoxyribonucleoside
4. Deoxyribonucleotide
1. Adenosine
2. Adenylate (AMP)
3. Deoxyadenosine
4. Deoxyadenylate (dAMP)
284
For the base Guanine, what is the corresponding:
1. Ribonucleoside
2. Ribonucleotide
3. Deoxyribonucleoside
4. Deoxyribonucleotide
1. Guanosine
2. Guanylate (GMP)
3. Deoxyguanosine
4. Deoxyguanylate
285
For the base Uracil/Thymine, what is the corresponding:
1. Ribonucleoside
2. Ribonucleotide
3. Deoxyribonucleoside
4. Deoxyribonucleotide
1. Uridine
2. Uridylate (UMP)
3. Thymidine
4. Thymidylate (TMP)
286
For the base Cytosine, what is the corresponding:
1. Ribonucleoside
2. Ribonucleotide
3. Deoxyribonucleoside
4. Deoxyribonucleotide
1. Cytidine
2. Cytidylate (CMP)
3. Deoxycytidine
4. Deoxycytidylate (dCMP)
287
What are the 7 uses of nucleotides?
1. Precursors of DNA and RNA
2. ATP
3. Adenine nucleotides are the components of 3 major coenzymes (NAD, FAD, Coenzyme A)
4. Activated intermediates
5. Metabolic and physiologic regulators
6. GTP is used in signal transduction pathways
7. CTP is used in the biosynthesis of glycerophospholipids
288
What is the De Novo pathway?
Activated ribose (PRPP) + amino acids + ATP + CO2 -> Nucleotide
289
What is the Salvage pathway?
Activated ribose (PRPP) + base -> Nucleotide
290
In the De Novo pyrimidine biosynthesis (UTP, CTP), pyrimidines are built from ?
Carbamoyl phosphate, aspartate, and PRPP
291
In the De Novo pathway of pyrimidine nucleotide (UMP and CMP) biosynthesis, what are the precursors?
Ribose-5-phosphate, CO2, Gln, Asp
292
What are the steps in the De Novo pathway of pyrimidine nucleotide (UMP and CMP) biosynthesis?
1. Synthesize carbamoyl phosphate
2. Build the pyrimidine ring (orotate) from aspartate
3. Link orotate to ribose-5-phosphate
293
What is the rate limiting step in pyrimidine synthesis and its corresponding enzyme?
Synthesis of carbamoyl phosphate, the enzyme is Carbamoyl Phosphate Synthetase II (CPS II)
294
Compare the metabolic process of CPS I to CPS II?
CPS I: urea synthesis
CPS II: pyrimidine synthesis
295
Compare the location of CPS I to CPS II?
CPS I: mitochondrial matrix
CPS II: cytosol
296
Compare the N donor of CPS I to CPS II?
CPS I: NH4+
CPS II: glutamine
297
Compare the regulator effectors of CPS I to CPS II?
CPS I: + = N-acetylGlu, arginine
CPS II: - = CTP, + = ATP, PRPP
298
Aspartate transcarbamoylase (ATCase) is an _______ regulated control point
allosterically
299
What is an inhibitor of ATCase? What is an activator of ATCase?
CTP, ATP
300
What yields orotate?
Ring closure and oxidation
301
The formation of PRPP from Ribose 5-phosphate uses what enzyme? This enzyme is highly regulated, but by ____ end products (not ______).
PRPP synthetase, purine, pyrimidines
302
Orotidylate decarboxylase catalyses formation of ? from orotidylate
uridylate
303
Both Orotate phosphoribosyl transferase and Orotidylate decarboxylase activities are found on a _____ polypeptide chain. The bifunctional enzyme is called ?
single, uridine monophosphate synthetase
304
Formation of CTP from UTP requires ______, ___ and the enzyme ?
glutamine, ATP, cytidylate synthetase
305
Pyrimidine Nucleotide Biosynthesis:
The pyrimidine ring is first synthesized to form ______. Then N1 of Orotate is covalently linked to C1 of the _____ using PRPP as the _____. ________ is the leaving group. Orotidylate is then enzymatically decarboxylated to form ____. ___ is then formed from UMP (__ ATP molecules are used up). Then ___ is formed by the addition of NH3 to UTP (from Glutamine).
orotidylate, ribose, precursor, pyrophosphate, UMP, UTP, 2, CTP
306
Ribonucleotide Reductase (RNR) makes deoxy NDP’s from ____
NDP’s
307
Note that dUDP and dUTP are dephosphorylated to ____, then converted to ___
dUMP, dTMP
308
Order these statements for the conversion of dUMP to dTMP:
1. N5,N10 methylene THF is then regenerated by the action of serine hydroxymethyl transferase.
2. THF is regenerated by reduction of dihydrofolate by dihydrofolate reductase using NADPH
3. Methylation of dUMP by 1-C (CH2) transfer (N5,N10 methylene THF)
3, 2, 1
309
How do chemotherapeutic agents work?
Inhibition of biosynthesis of DNA is the basis for some chemotherapies
310
Where is the impact caused by fluorouracil in THF synthesis?
Thymidylate synthase, in the conversion of dUMP to TMP
311
Where is the impact caused by trimethoprim in THF synthesis?
Dihydrofolate reductase, in the conversion of dihydrofolate to tetrahydrofolate
312
Fluorouracil is what kind of inhibitor?
Suicide
313
Methotrexate and Aminopterin are effective competitive inhibitors of _______
DHFR - dihydrofolate reductase
314
_______ has a 1000x fold greater affinity for DHFR than does dihydrofolate and is a competitive inhibitor
methotrexate
315
Methotrexate, aminopterin, and trimethoprim are also used to treat some _____ disorders such as rheumatoid arthritis and eczema
autoimmune
316
________ binds and inhibits both bacterial and protozoan DHFR enzymes very effectively (10^5 more so than Human DHFR).
Trimethoprim
317
_______ is often used in combination with other drugs to combat bacterial or protozoan infections.
Trimethoprim
318
______ is used to treat herpes simplex infections (various herpes viruses), and herpes zoster infections (chicken pox, shingles).
Acyclovir
319
Acyclovir is considered what kind of medication?
Antiviral
320
The following paragraph describes the Mechanism of action of what kind of medication?
Herpes viruses have a thymidine kinase which has a broad substrate specificity. Herpes TK, but not the human enzyme, will phosphorylate acyclovir. Acyclovir phosphate is a dGTP analog for the viral DNA polymerase. No 3’-OH group, hence after incorporation, termination of viral DNA synthesis.
Antiviral acyclovir
321
? : is a reverse transcriptase inhibitor which is a nucleoside analog. One component of an HIV cocktail.
Zidovudine and/or Azidothymidine
322
Zidovudine and/or Azidothymidine is considered what kind of medication?
Antiviral
323
The following paragraph describes the Mechanism of action of what kind of medication?
Cellular enzymes first convert azidothymidine to the 5’ triphosphate. Acts as a thymidine analog; gets incorporated into the DNA. Links to normal nucleotide 3-OH via its 5’ triphophate. The azido group on C3 the prevents further phosphodiester bond formation and DNA elongation.
Zidovudine and/or Azidothymidine
324
In the interconversion of nucleoside monophosphate kinase, its always the _______ that gets phosphorylated to the diphosphate, and its specific for the _____ not the sugar
monophosphate, base
325
What are the Three types of pathways in the Biosynthesis of Purine Nucleotides?
(1) De novo pathway (starting from the beginning)
(2) Salvage pathway (recycling bases)
(3) Very little is used from dietary sources
326
What are the 6 precursors for the de novo pathway is the Biosynthesis of Purine Nucleotides?
1. Ribose-5-P
2. Aspartate
3. CO2
4. Glycine
5. Glutamine
6. Formate
327
What is the main strategy in the biosynthesis of purine nucleotides?
Build the purine ring onto the ribose-5-P one atom or few atoms at a time
328
Formation of Inosinate then leads to formation of
______ and ______.
Adenylate, Guanylate
329
The first step in Purine Synthesis adds ______ to ? It is also highly _____
ammonia, C1 of ribose-5-P, regulated
330
What is the reaction of the first step in purine synthesis?
5-phosphoribosyl-1-pyrophosphate (PRPP) is converted to 5-phospho-β-D-ribosylamine, via glutamine-PRPP amidotransferase and the conversion of glutamine to glutamate and PPi
331
The product of the first step in purine synthesis is _____ and soon decomposes, so it has to be quickly utilized in the next step of the pathway. This reaction is regulated by ______ ______. Note, ______ is the origin of the amino group.
unstable, feedback inhibition, glutamine
332
There is ______ regulation of GMP and AMP synthesis: GTP is required for IMP → AMP, and ATP is required for IMP → GMP
Reciprocal,
333
Purine degradation results in ?
Uric Acid (Urate)
334
What is the purine degradation reaction resulting in uric acid?
Xanthine is converted to uric acid, and then urate via the enzyme xanthine oxidase
335
_____ is only moderately soluble, tends to crystallize if in excess, but it is a very good antioxidant.
Urate
336
_____ is characterized by high blood levels of uric acid or urate due to overproduction or underexcretion of uric acid
Gout
337
Uric acid crystals deposit in joints causes ?
pain and inflammation, essentially arthritis
338
What is the treatment for gout?
Drugs. e.g. allopurinol
339
Allopurinol reacts with xanthine oxidase to produce ______, which is an inhibitor of xanthine oxidase
Oxypurinol
340
Most purines from diet are converted to ? which is (hopefully) excreted
uric acid
341
What are the two main enzymes used in the salvage pathways for purine nucleotide biosynthesis?
Adenine phosphoribosyltransferase (APRT), this is the minor enzyme of the two
Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
342
What is Lesch Nyhan Syndrome?
Deficiency in HGPRT activity due to mutations in the gene
343
Lesch Nyhan Syndrome is an X-linked disease, thus primarily affects ____
males
344
? comes with severe intellectual deficits, motor dysfunction, self-mutilation, and very aggressive behavior. The combination of increased synthesis and decreased utilization of purines leads to high levels of uric acid production
Lesch Nyhan Syndrome
345
What is the most dangerous aspect of Lesch Nyhan Syndrome?
It does not respond to allopurinol treatment
346
What is a major aspect of the intricate regulation and integration of metabolic pathway?
Allows metabolic pathways to respond rapidly to the needs of the cell/organism
347
What are the 5 most common mechanisms of regulation in metabolic pathways?
1. Allosteric modulators
2. Covalent modification
3. Proteolysis
4. Induction or repression of enzyme synthesis
5. Compartmentalization
348
Hormones are signals from outside the cell that allow communication between ____ and ____ as well as integrate and coordinate the metabolic activities of ______ _____
cells, tissues, different tissues
349
The human body uses and regenerates approximately its own body weight in ATP per day, which corresponds to about __-__kg of ATP/day
50-75
350
What are the 3 sources of carbohydrates, fat, and proteins?
1. Diet
2. Circulating Fluid (blood)
3. Stored fuel
351
There are 6 sources of carbohydrates, fat, and proteins from circulating fluid (blood):
1. Glucose from diet and ______
2. Lactate from _____ metabolism
3. Glycerol and fatty acids from ? in adipose tissue
4. Ketone bodies synthesized in the ____
5. Triacylglycerol transported as ?
- ____ contains triacylglycerol from dietary fatty acids
- ____ contains triacylglycerol produced in the liver
6. Amino Acids from ___ or ______ of body proteins
1. gluconeogenesis
2. anaerobic
3. lipolysis of triacylglycerol
4. liver
5. plasma lipoprotein, chylomicron, VLDL
6. diet, proteolysis
352
Stored fuel comes in 3 different forms: ?
1. Glycogen
2. Triacylglycerol
3. Proteins
353
How much liver glycogen in grams compared to muscle glycogen?
Liver: ~100g
Muscle: ~500g
354
How much triacylglycerol in the body in grams?
~15000
355
Triacylglycerol is the ____ of stored energy in the body, and can be stored in virtually ______ amounts
bulk, unlimited
356
How much protein in the body in grams?
~6000
357
Stored fuel in protein form has no storage form independent of ______
function
358
_________ are the most highly concentrated form of stored biological energy
Triacyclglycerols
359
Tissues and organs have specialized functions and, therefore, they have different ____ _______ and ?
fuel requirements, patterns of metabolism
360
Type of fuel utilized by these tissues vary with the ______ and _______ states of the individual, and level of _____
nutritional, hormonal, activity
361
Brain and RBC only use ____ as energy source
glucose
362
The brain, given its small size, utilizes a big proportion and overconsumption of _____
glucose
363
Some organs function as substrate/energy providers: such as the ___ and ? ensure that consumer organs, especially _____, ____, and ? are always supplied with fuel.
liver, white adipose tissue, brain, muscle, red blood cells
364
The _____ ____ absorbs nutrients from the diet; moves them into blood or lymphatic system
small intestine
365
The _____ ___ carries nutrients from intestine to liver
portal vein
366
The _____ processes fats, carbohydrates, proteins from diet; synthesizes and distributes lipids, ketone bodies, and glucose for other tissues; converts excess nitrogen to urea
liver
367
The ______ secretes insulin and glucagon in response to changes in blood glucose concentration
pancreas
368
The _____ transports ions to maintain membrane potential; integrates inputs from body and surroundings; sends signals to other organs
brain
369
The _____ _____ uses ATP generated aerobically to pump blood
cardiac muscle
370
The _____ _____ carries lipids from intestine to liver
lymphatic system
371
The _____ ____ synthesizes, stores, and mobilizes triacylglycerols.
adipose tissue
372
The ____ _____ uses ATP generated aerobically or anaerobically to do mechanical work
skeletal muscle
373
Glucokinase in liver is not inhibited by ?
G6P (glucose-6-phosphate)
374
_____ has high capacity for glucose uptake
Liver
375
? is at the crossroads of carbohydrate metabolism in the liver
Glucose 6-phosphate
376
Glucose export is used to maintain blood [glucose] for use by ____
brain
377
In liver, during the ___ state, glucose is used for conversion to ATP, glycogen, fatty acids, cholesterol, NADPPH, and nucleotides; but in the ____ state, glycogen and gluconeogenesis is used to generate glucose
fed, fasting
378
Liver acts as a glucose _____
sensor
379
Liver acts as a glucose sensor and there are three features contribute to this:
1. Liver has a specific glucose transporter, ____, which has a high ___ for glucose which means it can respond to increasing glucose concentrations
2. Liver also has a specific hexokinase called ______; it too has a high Km for glucose and is not inhibited by _______
3. Liver glycogen phosphorylase a is inhibited by ______
GLUT2, Km, glucokinase, glucose-6-P, glucose
380
In liver, during the ___ state, amino acids are converted to proteins, nucleotides, or are exported; but in the ____ state, amino acids are used to make glucose and ATP
fed, fasting
381
In liver, during the ___ state, fatty acids are converted to triacylglycerol and phospholipids; but in the ____ state, fatty acids are converted to ATP and ketone body production
fed, fasting
382
A major role of the liver is to produce fuel from nutrients taken up from blood to be used by ?
other organs
383
The liver takes up _____ and _____ released from muscle and glycerol released from adipose to synthesize glucose via gluconeogenesis
alanine, lactate
384
There is no significant ____ in the brain
glycogen
385
In brain, during the ___ state, glucose is converted to ATP; but in the ____ state, glucose and ketone bodies are used for ATP
fed, fasting
386
During prolonged fasting, ketone bodies can provide as much as ___% of the energy in the brain
70
387
In fat cells, during the ___ state, glucose is converted to ATP, NADPH, as well as Acetyl CoA and DHAP, which are converted to Fatty acyl CoA and glycerol 3P, fatty acids are converted to triacylglycerol; but in the ____ state, lipolysis occurs
fed, fasting
388
In fat cells, most ATP needs are met through ?
β-oxidation
389
What are myocytes?
Skeletal muscle cells
390
Since muscle lacks glucose-6-phosphatase, the glucose released from glycogen is metabolized
through ____
glycolysis
391
Some lactate in blood is used by heart and oxidized to CO2; has specific isozyme of LDH which favors conversion to _____
pyruvate
392
At _____ activity in skeletal muscle cells, glucose is converted to ATP and lactate, glycogen to glucose, and fatty acids to ATP
maximum
393
In skeletal muscle cells during the _______ state, fatty acids are converted to ATP
resting
394
The heart obtains most of its ATP through ______ ______ using fatty acids
oxidative phosphorylation
395
Insulin, glucagon and epinephrine are the major metabolic hormones: ______ and _____ are synthesized and stored in the pancreas while _____ is synthesized in the adrenal gland
insulin, glucagon, epinephrine
396
Insulin, glucagon, and epinephrine are termed _____ hormones which means they are secreted into the blood to act on other tissues including the major metabolic organs discussed already
endocrine
397
Its important to note that insulin, glucagon, and epinephrine do not necessarily have effects on all tissues, only those that have ?
receptors on their cell surface
398
Insulin, glucagon, and epinephrine ensure that adequate fuels are available for the different
tissues in the body or that dietary nutrients are properly stored and metabolized → ?
maintain metabolic homeostasis
399
Because insulin, glucagon, and epinephrine can simultaneously act on different tissues, they can
coordinate metabolic processes to more effectively achieve the ?
desire effect
400
The primary signal for insulin secretion is ____; fatty acids and some specific amino acids can augment this , so insulin levels rise shortly after eating and signal the fed state
glucose,
401
Since sustained high levels of glucose in blood is damaging to cells, the metabolic effects of insulin are related to _____ blood glucose and to properly manage, store, metabolize this nutrient
lowering
402
One of the primary, initial effects of insulin is to stimulate glucose ___ into cells
uptake
403
Insulin: __ glucose uptake, __ glycolysis, __ acetyl-CoA production, __ glycogen synthesis, __ triacylglycerol synthesis, __ gluconeogenesis, __ lipolysis
Signals fed state: __ blood glucose level, __ fuel storage, __ cell growth and differentiation
↑, ↑, ↑, ↑, ↑, ↓, ↓, ↓, ↑, ↑
404
The primary signal for glucagon release from the pancreas is a ____ in blood glucose levels
drop
405
A major action of glucagon is to stimulate _____ of glucose from liver by activating glycogenolysis and gluconeogenesis
release
406
Glucagon also stimulates _____ which provides an additional brain fuel to take some pressure of glucose usage
ketogenesis
407
Glucagon also stimulates ? in adipose, which release fatty acids which can be used as an alternative fuel by many tissues, again taking the pressure off of glucose usage
TAG breakdown
408
Glucagon: __ cAMP level, __ glycogenolysis, __ glycogen synthesis, __ triacylglycerol hydrolysis and mobilization, __ gluconeogenesis, __ glycolysis, __ ketogenesis
Signals fasting state: __ blood glucose level, __ glucose release from liver, __ ketone bodies as an alternative fuel for brain
↑, ↑, ↓, ↑, ↑, ↑, ↓, ↑, ↑, ↑, ↑
409
_______ is released from adrenal glad under stressful situations that require energy
Epinephrine
410
The main target organs of ______ are liver, muscle and adipose, which provide fuel for the muscle to produce ATP
epinephrine
411
In ______, epinephrine stimulates glycogen breakdown and glucose release; in ____, epinephrine stimulates TAG breakdown and fatty acid release; in ______, epinephrine stimulates glycogen breakdown and glycolysis
liver, adipose, muscle
412
Epinephrine: __ cAMP level, __ glycogenolysis, __ glycogen synthesis, __ triacylglycerol mobilization, __ glycolysis
Signals stress: __ blood glucose level, __ glucose release from liver
↑, ↑, ↓, ↑, ↑, ↑, ↑
413
The normal blood glucose (mg/100mL)
60-90, or ~3mM to ~5mM
414
What is "hypoglycemic"?
Anything less than 40mg/100mL, causes lethargy, convulsions, and coma
415
What happens if your blood glucose goes below 10mg/mL or ~0.5mM?
If prolonged, permanent brain damage, and death
416
What is "hyperglycemic"?
Anything above 140mg/100mL, causes cataract, convulsion, coma, death
417
What is the "Early Phase" in the 3 phases of starvation?
1 day
418
In the ____ phase: glucagon levels rise in response to dropping glucose, insulin goes down; glucose uptake decreases to preserve for brain; gluconeogenesis and glycogenolysis in liver stimulated; no problem maintaining blood glucose; TAG hydrolysis in adipose is mildly stimulated, glycerol released is substrate for gluconeogenesis while fatty acids energy source for many tissues; metabolically this is an easy challenge to handle
early
419
What is the "Mid Phase" in the 3 phases of starvation?
2-3 weeks
420
In the ____ phase: liver glycogen now completely depleted; body tries to lower its utilization of glucose; TAG hydrolysis in adipose is further elevated; but amount of glycerol released is inadequate to provide sufficient substrate for gluconeogenesis; as a result, muscle degradation begins which releases amino acids; glucagon stimulates ketone body production; excessive fatty acid oxidation in liver provides lots of acetyl CoA substrate; brain derives about a third of its energy from ketone bodies
Mid
421
Muscle wasting actually begins about Day __ of starvation
3
422
What is the "Late Phase" in the 3 phases of starvation?
>3 weeks
423
In the ____ phase: TAG hydrolysis in adipose continues to provide most of the body’s energy needs; muscle degradation slows dramatically in attempts to spare whatever muscle remains; this reduces glucose production; ketone body production increases even further; brain derives about two-third of its energy from ketone bodies; this phase lasts depends on the size of the fat depot
Late
424
The degradation of non-muscle cellular protein produces many symptoms, people often die from an _____ _____ rather than directly from ______ although reduction in heart function does occur
infectious disease, starvation
425
_______ _____ is the collective name for a group of disorders characterized by persistent hyperglycemia
Diabetes Mellitus
426
_____ _____ is the leading cause of adult blindness, amputation, renal failure, heart attack and stroke
Diabetes Mellitus
427
What is the fasting glucose blood level in Diabetes Mellitus?
> 7mM
428
The major effects of ______ include: urinary loss of H2O, glucose, electrolytes, dehydration of cells, cellular malfunction and can cause coma, glycation of plasma proteins (HbA1c), cataracts
hyperglycemia
429
What are the 2 tests that can help diagnose Diabetes?
1. Glucose tolerance test
2. Blood HbA1C test
430
What is the Glucose tolerance test?
Drink glucose solution, measure blood [glucose] over a period of several hours
431
What is the Blood HbA1C test?
HbA1C test result reflects your average blood sugar level for the past two to three months, and measures the amount of blood sugar attached to your hemoglobin proteins (glycated)
432
The ____ your A1C level is, the poorer your blood sugar control and the higher your risk of diabetes
higher
433
What are the 2 main aspects of Type 1 Diabetes Mellitus?
1. Insulin-Dependent Diabetes Mellitus (IDDM)
2. Juvenile onset
434
What are the 2 main aspects of Type 2 Diabetes Mellitus?
1. Non-insulin-Dependent Diabetes Mellitus (NIDDM)
2. Maturity onset
435
Type __ Diabetes Mellitus accounts for ~10% of diabetics and is characterized by deficiency of insulin
1
436
Type __ Diabetes Mellitus is caused by an autoimmune attack of the β-cells of pancreas due to: environmental factors or genetic determinants that allow cells to be recognized as “non-self” by the immune system
1
437
Clinical characteristics of Type __ Diabetes Mellitus:
o frequent urination (polyuria)
o excessive thirst (polydipsia)
o excessive hunger (polyphagia)
* usually accompanied by fatigue and weight loss
1
438
What is the treatment for type 1 Diabetes Mellitus?
Insulin therapy to regulate blood glucose
439
In diabetes, there is hyperglycemia due to:
__ glucose uptake, __ glycogen breakdown, __ gluconeogenesis. There is also a __ ketone bodies
↓, ↑, ↑, ↑
440
Your body thinks it is starving because there is no glucose entering cells, so insulin therapy aims to __ glucose uptake
↑
441
___ ketone body production in diabetics can be lethal
Excess
442
Ketone bodies are moderately strong acids, and excess production can lead to _____. In untreated diabetics, there can be overproduction of ketone bodies, leading to ______ ______
acidosis, diabetic ketoacidosis
443
If insulin is absent or not functioning, glucose cannot enter cells. All energy must be derived from ____, leading to the production of _____ ___
fats, acetyl CoA
444
In diabetics, _______ is used for glucose production, so there is insufficient amounts to react with acetyl CoA from fatty acid oxidation. Instead, _____ __ builds up because oxaloacetate is not available to replenish the TCA cycle. Result is that acetyl CoA is utilized for ?
oxaloacetate, acetyl CoA, ketone body production
445
In diabetics, KB _____ > KB ______
Synthesis, Oxidation
446
Low fat diet still contains lots of ________: dietary _______ are broken down into glucose, _____ blood glucose levels. Insulin is secreted from pancreas and stimulates glucose _____. Promotes fat storage
carbohydrates, carbohydrates, raising, uptake
447
In the keto/ketogenic diet, most calories come from ___ and very little _______
fats, carbohydrates
448
Goal in the keto/ketogenic diet is to reduce body weight and get rid of excess triacylglycerol from adipose tissue by stimulating _____ and ? by restricting carbohydrate intake so ____ not secreted. Glucagon/epinephrine is secreted which activates lipolysis so the body’s primary fuel source shifts from _____ to ____
lipolysis, fatty acid oxidation, insulin, glucose, fat
449
With the keto diet, you want to stimulate _____, but not ______
ketosis, ketoacidosis
450
What is ketosis?
Production of ketone bodies
451
What is ketoacidosis?
Very high levels of ketone bodies in the blood, ↓ blood pH leads to coma, death, which can happen if not enough caloric intake is too low
452
In the keto diet there are beneficial metabolic changes (short-term) which does lead to weight loss, __ hunger, __ energy expenditure, __ fat loss vs protein. But there are some pitfalls: hunger, fatigue, low mood, irritability, constipation, kidney stones, nutrient deficiencies, headaches, brain “fog,” ↑ uric acid in the circulation can cause gout
↓, ↑, ↑
