Amino Acid Metabolism Flashcards
(106 cards)
1
Q
What are the sources of aminoacids in the body?
A
- Dietary
- Body protein break down
- De novo synthesis of non essential amino acids
2
Q
Amino acids in the body are consumed in ….., ….. and ……
A
- break down to CO2 and H2O
- Synthesis of body proteins
- Synthesis of specialized products (hormones, enzymes, neurotransmitters)
3
Q
The amino acids …… & ….. are essentials only in children and infants
A
Arginine, histidine
4
Q
Name the essential amino acids in humans
Hint: Pvt. Tim Hall
A
Phenylalanine, valine, threonine, tryptophan, isoleucine, methionine, histidine, arginine, leucine, lysine
5
Q
Humans are unable to synthesize these 3 types of amino acids
A
- Basic amino acids
- Aromatic ring system in amino acids
- Branched chains amino acids
6
Q
The major drain on the amino acids pool is ……
A
protein synthesis, with about 300 grams synthesized every day
7
Q
Healthy adult protein requirement is …..
A
- 8 g/kg per day
* Exogenous protein source is required to maintain the amino acid pool
8
Q
Protein degradation starts in the …… by the action of ……
A
- Stomach
2. Pepsin (which is activated by the gastric acid
9
Q
Pepsin function is to ……
A
degrade proteins into large peptides
10
Q
Inactive pancreatic proteases are activated by the enzyme ……
A
enteropeptidase
- Pancreatic proteases are (trypsin, chymotrypsin, elastase, carboxypeptidase)
- Trypsinogen is the one who is activated first, and then in turn activates the rest of the enzymes
11
Q
Pancreatic proteases hydrolize proteins into …..
A
aminoacids, dipeptides, tripeptides
12
Q
What happens to small peptides upon transport into the intestinal cells?
A
They are hydrolyzed into amino acids before they leave the cells
13
Q
Aminoacid transport are ……. dependent in the luminal surface
A
Sodium
* Na+ independent in the contraluminal membrane
14
Q
Degradation of amino acids starts by ….
A
removal of the alpha-amino group
* %85 of the amino nitrogen is disposed of in urea
15
Q
What are the reactions needed to transport the nitrogen from amino acids to urea?
A
- Transamination
2. Oxidative deamination of glutamate
16
Q
What are Transaminases?
A
Enzymes that transfer alpha-amino group to an acceptor.
- Transaminases are specific for the aminoacids, but not for the acceptors
- Lysine, serine and threonine are not transaminated
see. p. 344
17
Q
The acceptor in the transaminases reactions is usually …..
A
an alpha-keto acid
* like alpha-keto glutarate
18
Q
What is the role of pyridoxal phosphate in transamination?
A
It acts as a transient carrier in the reaction
* same as B 6 (pyridoxine)
19
Q
Pyridoxal phosphate is the derivative of ……
A
B6 (pyridoxine). It acts as a coenzyme for all transamination reactions
20
Q
What are the fates for glutamate?
A
In the liver, the alpha-amino group may be released as free ammonia, or transferred to oxaloacetate
21
Q
Describe the oxidative deamination for glutamate
A
the reaction is catalyzed by glutamate dehydrogenase (in the mitochondria)
Glutamate + NAD (gives) alpha-ketoglutarate + NADH + NH4
* Ammonium is released from glutamate, making it available for urea synthesis
see p. 345
22
Q
Describe oxaloacetate transamination
A
some alpha-amino acids are transferred from glutamate to oxaloacetate, forming aspartate. This reaction occurs in the cytosol of the liver/muscle/brain/RBC/heart, and is catalyzed by AST (aka glutamate:oxaloacetate transaminase)
* Aspartate will act as urea donor in urea synthesis
* Increased AST may suggests hepatitis, MI, renal disease
see p. 345
23
Q
Urea synthesis occurs in the ….
A
liver
* Excreted by the kidney
24
Q
Urea is composed of ……..
A
two amino groups and one carbonyl. One amino comes from ammonium and the other from aspartate. The carbonyl comes from bicarbonate
25
The synthesis of 1 mol of urea requires ...... enzymes and ..... ATPs
five, three
| * NH4 + 3ATP + HCO3 + aspartate (gives) urea + fumarate + 2ADP + AMP + 2Pi + PPi
26
The first two reactions in urea cycle occurs in the ......, the rest is in the .....
mitochondria
| cytosol
27
The enzyme ..... catalyzes the first reaction in urea synthesis
carbamoyl phosphate synthetase I
* NH4 + 2ATP + HCO3 (gives) carbamoyl phosphate
* This is the rate limiting step in urea synthesis
28
The enzyme .... catalyzes the second reaction in urea synthesis
ornithine transcarbamoylase
| * Carbamoyl phosphate + ornithine (gives) citrullin
29
The enzyme ........ synthesizes arginosuccinate from citrulline
Arginosuccinate synthetase
| * Citrulline + Aspartate + ATP (gives) Arginosuccinate
30
Arginosuccinate lyase cleaves arginosuccinate into .... and .....
fumarate, arginine
| * Furmarate enters TCA cycle
31
The enzyme arginase cleave arginine into ..... and .....
urea and ornithine
| * ornithine is transported back into the mitchondria to be used in another urea synthesis cycle
32
Carbamoyl phosphate synthetase is allosterically activated by .....
N-Acetyl glutamate, which is formed when glutamate accumulates in the mitochondria after a protein rich meal
33
Carbamoyl phosphate synthetase II is a .....
cytosolic enzyme involved in pyrimidine synthesis. Uses glutamate as a nitrogen donor
34
Arginase enzyme is found only in .....
liver, brain and kidney
35
Enzymes deficiency in the urea cycle leads to accumulation of
ammonia. . most notably in CPS-I and OTCase deficiency
| * Ammonia accumulates in liver cirrohsis. It is fatal since there is no alternative pathway
36
Skeletal muscles uses ..... as a carrier to transfer amino groups to the liver where it participates in urea synthesis
alanine
37
The enzyme alanine aminotransferase catalyzes the transfer of amino group from ..... to ...... in skeletal muscles
glutamate to pyruvate
* The formed alanine is transferred to the liver, glutamate is reformed and used in urea synthesis. Pyruvate is used in gluconeogenesis
* This enzyme is also called glutamate:pyruvate transaminase
* Increased ALT levels may suggests acute hepatitis
38
Alanine amino transferase in both skeletal muscles and the liver is found in the mitochondria. T/F
False. It is a cytosolic enzyme
39
In extrahepatic tissues, it is important to detoxify free ammonia by formation of ......
glutamine
* glutamate + NH4 + ATP (gives) glutamine + ADP + Pi
* This reaction is important in tissues that can't synthesize urea
40
What is the fate of glutamine ??
it is taken up by the liver and the kidney
| see p. 348
41
Ammonia in glutamine is removed by two enzymes, ..... & ......
glutaminase and glutamate dehydrogenase
* Both of these enzymes are in the mitochondria
* In the liver, ammonia is incorporated in urea, in the kidney it is secreted in urine as ammonium (important in titration of H+)
42
What is the fate of the carbon skeleton in amino acids degradation?
1. Oxidized to CO2 and H2O and generate energy
| 2. Used to synthesize glucose or ketones
43
All amino acids are broken down to 7 metabolites. List
Acetyl-CoA, Acetoacetyl-CoA, pyruvate, succinyl-CoA, fumarate, oxaloacetate, alpha-ketoglutarate
44
Some amino acids are glucogenic and ketogenic, like ....
isoleucine, phenylalanine, tyrosine, tryptophan
45
Strict glucogenic amino acids are
All but the ketogenic and the mixed
46
Degradation of branched chain amino acids occur mainly in the ..........
skeletal muscles, where transaminase activity is high
47
The enzyme ........... catalyzes the transfer of amino group from branched amino acid to alpha-ketoacid with the formation of glutamate
Branched chain aminoacid transaminase (BCAA transaminase)
48
The branched alpha ketoacids are decarboxylated by the enzyme .......
Branched chain ketoacid dehydrogenase (BCKA-DH), the result is branched chain acyl-CoA analogs
Valine : succinyl-CoA
Isoleucine: Propionyl-CoA and Acetyl-CoA
Leucine: Acetoacetyl-CoA
see p.349
49
BCKA-DH complex is similar to ........ and requires the same five coenzymes
Pyruvate dehydrogenase
50
Propionyl-CoA is the result of ........ degradation
Isoleucine, methionine, threonine
| * Also, comes from oxidation of odd number fatty acids (from the omega end)
51
Propionyl-CoA needs what enzymes to be converted to succinyl-CoA?
1. Propionyl-CoA carboxylase
2. Methmalonyl-CoA mutase
see p. 350
52
Propionic aciduria results from deficiency of ......
| Methymalonyl-CoA aciduria results from deficiency of ...............
1. Propionyl-CoA carboxylase or biotin
2. Methmalonyl-CoA mutase or B12
see p. 350
53
Non essential amino acids are synthesized from intermediates ...... or ......
glycolysis or essential amino acids
54
Phosphoglycerate is a precursor for ....... amino acid
glycine and serine
55
Transamination of pyruvate gives ......., while oxaloacetate & alpha-ketoglutarate give ....... & ....... respectively
alanine
| aspartate, glutamate
56
Addition of amide group to the side chain of aspartate & glutamate give ...... & ...... respectively
Aspargaine, glutamine
57
Tyrosine and cysteine are synthesized from the essential amino acids ...... & ..... respectively
Phenylalanine, methionine
58
Phenylalanine hydroxylase deficiency leads to
phenylketonuria
* There is musty body odor and mental retardation. Minimal melanine production causing light skin, hair & blue eyes
* Tx is removal of phenylalanine from diet, including aspartame
* PKU is characterized by high levels of Phenylalanine in blood and its by products in urine (phenylpyruvate, phenyllactate, phenylacetate)
59
Tyrosine synthesis requires .........., and the enzyme .......
phenylalanine, phenylalanine hydroxylase
60
Phenylalanine hydroxylase requires ...... & ......
O2, tetrahydrobiopterin
* THB is oxidized to DHB in the reaction. It must be reduced back to THB by NADPH and reductase for the synthesis reaction to continue
61
The sulfur in cysteine is derived from ......., while the rest of the cysteine molecule is derived from .......
methionine, serine
62
Describe the reaction for converting methionine into cysteine
1. methionine is first converted into homocysteine
2. Addition of serine catalyzed by cystathionine synthase and B6 to form cystathionine
3. Cystathionase cleaves cystathionine into cysteine, NH4 and alpha-ketobutyrate
63
The enzyme methionine synthase converts ...... back to methionine using ......
homocysteine, B12 and THF as a methylating agent
| * This is one of the two reactions in humans that requires B12
64
What are the causes for homocysteinuria?
1. Inherited deficiency of methionine synthase, cystathionine synthase
2. Acquired B12, B6 and folate deficiency
65
What is the cause of cystathioninuria?
Deficiency of pyridoxine (B6) or cystathionase
66
Arginine is formed by cooperation between ..... and ......
intestine and kidney
67
The first two enzymes in the urea cycle are found in the ......... . The rest of the enzymes are found in .......
mitochondria of intestinal cells, kidney
68
There is approximately ..... grams of free amino acids in the body, of which ..... percent is essential amino acids
100 grams
| 10%
69
What are the differences between CPS-I and CPS-II
CPS-1: in the mitochondria, catalyzes the condensation of NH4 and HCO3 in the urea cycle
CPS-II: in the cytosol, catalyzed reactions of pyrimidine synthesis
70
What are the results of these deficiencies:
1. CPS-I
2. Arginosuccinate lyase
3. Arginosuccinate synthase
4. OTCase
1. Type I hyperammonia: increased ammonia, alanine and glutamine
2. Arginosuccinate aciduria
3. citrullinemia
4. Type II hyperammonia: increased ammonia, glutamine
71
The products of breakdown of leucine and lysine is used by nerve cells for
lipid production
72
What are the most common reactions for the synthesis of specialized products from amino acids?
decarboxylation: requires B6
hydroxylation: requires THB as a reductant
methylation: requires SAM as a methylating agent
73
SAM is synthesized by the condensation of ....... and ......
ATP & methionine
| * SAM has much higher reducing power than THF
74
Decarboxylation of histidine results in ......
histamine
| * Histamine is synthesized in mast cells of connective tissue near blood vessels
75
GABA is produced by ......
decarboxylation of glutamate
| * GABA is an inhibitory neurotransmitter
76
Serotonine is synthesized by .......
hydroxylation of tryptophan, then decarboxylation
| * Serotonine is a potent vasoconstrictor
77
Catecholamine is a neurotransmitter in ....., and a hormone in ......
brain
| the adrenal medulla
78
Catecholamines are rapidly degraded by ...... & ......
monoamine oxidase & catechol-O-methyl transferase
79
Tyrosine hydroxylase and dopamine hydroxylase have different cofactor requirement in catecholamine synthesis. T/F
True
* Tyrosine hydroxylase requires THB & O2 to convert tyrosin to DOPA
* Dopamine hydroxylase requires Cu & ascorbate to convert dopamine into norepinerphrine
80
Parkinson's results from deficiency of ...... It is treated by ...... & ......
dopamine
treated with L-DOPA (levodopa) & carbidopa
* L-DOPA crossed the BBB to be decarboxylated to dopamine
* L-DOPA peripheral effect is inhibited by carbidopa, which inhibits DOPA decarboxylase. Carbidopa does not cross the BBB
81
Melanin is produced by hydroxylation of ...... and requires .... & ..... as cofactors
tyrosine
Cu & ascorbate
* Deficiency of tyrosine hydroxylase (tyrosinase) causes albinism. Individuals are prone to sun induced skin cancer (SCC & melanoma & basal cell carcinoma)
82
Thyroxine synthesis requires ...... & ......
tyrosine rich thyroglobulin & iodide uptake
| * Iodide must be oxidized to iodine
83
The incorporation of one iodine in the tyrosine side chain produces ....., while two iodine produce ......
```
monoiodinated tyrosine (MIT)
diiodinated tyrosine (DIT)
```
84
Covalent cross linking of two DIT produces ....., while one DIT and one MIT produces ....
tetraiodothyronine (T4)
| triiodothyronine (T3)
85
Nitric oxide is synthesized from ...... by the action of ..... . It is found in ...... where it causes ..... by increasing ......
arginine
nitric oxide synthase (requires THB and O2, forms NO & citrullin from arginine)
endothelial cells of small blood vessels
relaxation
cGMP
* It is called "endothelium derived relaxing factor"
* It has a 5 seconds half life
* Also has a role in macrophage activity (its metabolite are toxic to ingested organisms)
86
Creatine is synthesized from ...., .... & ..... .
arginine, SAM & glycine
87
Creatine phosphate is the storage form of ......
High energy phosphate in skeletal muscles. It is degraded rapidly by the action of creatine phosphokinase (CPK) to produce ATP
88
The amount of creatinine excreted in urine is proportional to ....... .
Creatinine level in blood is used to ......
muscle mass
| assess kidney function or estimate muscle mass
89
In heme synthesis, the porphyrin ring is formed from .... & .....
glycine & succinyl-CoA
90
The rate limiting step in heme synthesis is the formation of ...... catalyzed by ..... and inhibited by .....
aminolevulinate, aminolevulinic acid synthase
* This reaction requires B6
* The synthesis is inhibited by heme
91
Condensation of two aminolevulinate forms ...... . This reaction is catalyzed by ......
porphobilinogen
catalyzed by ALA dehydratase
* This is the first intermediate with a pyrrole ring
92
Condensation of four porphobilinogen forms ....
uroporphyrinogen
| * Catalyzed by uroporphyrinogen synthase
93
The addition of ...... to protoporphyrin IX forms heme
Iron
| * The reaction catalyzed by ferrochetolase (called heme synthase)
94
What are the reactions that require B12 as a coenzyme ?
1. Conversion of methymalonyl-CoA to succinyl-CoA
| 2. Conversion of homocysteine to methionine
95
Heme degradation occurs in the ..... by the action of ...... which opens the ........ and forming .......
reticuloendothelial cells
heme oxygenase
pyrrole ring
biliverdin & CO
96
What is the one and only reaction in humans that forms CO?
Oxygenation of heme to biliverdin
97
In the liver, biliverdin is reduced to ...... by the action of ......
bilirubin, biliverdin reductase & NADPH
98
Conjugation of bilirubin with ...... greatly increases its solubility, forming .....
glucouronate (catalyzed by UDP-glucuronyl transferase)
bilirubin diglucuronide
* This is called direct bilirubin, while the unconjugated is called indirect
99
Bilirubin is excreted in the feces as ..... and in the urine as .....
stercobilin
| urobilin
100
What are the causes of jaundice (hyperbilirubinemia)?
excessive hemolysis, bile obstruction or liver damage
101
All non essential amino acids are derived from intermediates in the ....... except tyrosin, which is derived from .....
TCA
| phenylalanine
102
Deficiency of homogentisic acid oxidase causes ......., which is characterized by ...
alkaptonuria
black urine & pigmented sclera
* homogentisic acid (aka melanic acid) is an intermediate in the breakdown of tyrosine
103
Albumin is synthesized by ......, and its functions are .....
liver (60% of plasma proteins)
| * Maintains plasma osmotic pressure, transport of molecules (drugs, Ca, steroid hormones, copper, free fatty acids)
104
Globulins synthesized by the liver is three types, list..
1. Alpha: forms HDL, prothrombin, angiotensinogen
2. Beta: forms LDL
3. Gamma (not synthesized by the liver): forms immunoglobulins
105
Hemoglobin is composed of ...... & ......
1. Heme: 4 groups, each has 4 pyrrole & one Fe+2
| 2. Globin: one group composed of 2 alpha & 2 beta chains
106
What is the difference between hemoglobin and myoglobin??
Hemoglobin (RBC) has four heme groups
| Myoglobin (muscles, red) has one heme group (accepts only one O2), with higher O2 affinity than Hb
