Amino Acid Catabolism Flashcards
1
Q
describe the reaction between amino and keto acids (2)
A
- reversible reaction
- direction of reaction determined by concentration of each within a cell
2
Q
which keto acid is the catalytic component in the TCA cycle and why? (2)
A
- alpha-ketoglutarate
- it is not regenerated
3
Q
what are the main ketoacid - amino acid pairs? (3)
A
- alpha-ketoglutarate and glutamate
- oxaloacetate and aspartate
- pyruvate and alanine
4
Q
what are the sources of amino acids for catabolism? (3)
A
- ingested amino acids in excess of the body’s need for protein synthesis
- normal protein turnover
- during starvation (or uncontrolled diabetes) when carbohydrates are not available or can not be properly utilized
5
Q
nitrogen balance equation and its possible values (4)
A
nitrogen balance = nitrogen ingested - nitrogen excreted
- zero: ideal, protein synthesis = protein degradation
- positive: protein synthesis > protein degradation
- negative: protein synthesis < protein degradation
6
Q
in what situations are nitrogen balance positive or negative? (2)
A
- positive: during immune response, pregnancy, exercise, injury repair
- negative: starvation
7
Q
what happens when dietary protein enters the stomach? (2)
A
- stimulates production of gastrin hormone
- gastrin hormone causes secretion of HCl (lowers pH) and pepsinogen (a zymogen)
8
Q
what is a zymogen?
A
- the storage form of a protease
9
Q
how does pepsinogen contribute to the digestion of protein? (2)
A
- pepsinogen turns into pepsin, a protease, at low pH
- pepsin starts degrading proteins at amino terminal side of aromatic amino acids
10
Q
what happens to proteins as they leave the stomach and enter the small intestine? (2)
A
- the pancreas secretes secretin which induces release of bicarbonate
- bicarbonate neutralizes HCl in the low pH contents
11
Q
- what is the pancreas’ role in protein digestion (3)
A
- secretion of secretin to neutralize HCl
- releases zymogens which are converted to active proteases by enteropeptidase, a proteolytic enzyme secreted by intestinal cells
- these and other proteases degrade most proteins to their component amino acids (proteases have different specificities to target different functional groups)
12
Q
how are digested proteins absorbed by the body? (2)
A
- they enter intestinal cells through a transporter as they are polar and cannot diffuse freely, but not much energy is required for transport
- they exit intestinal cells through a transporter and enter the blood
13
Q
where do dietary nitrogen and carbon skeletons go after they are absorbed? (2)
A
- nitrogen goes toward the urea cycle
- carbon skeletons go toward the citic acid cycle
14
Q
NH4+
A
- ammonium
15
Q
NH3
A
- ammonia
16
Q
how is NH4+ produced in the body?
A
- amino acid degradation, which occurs in all cells of the body
17
Q
how is NH4+ carried in the bloodstream?
A
- NH4+ is carried in the form of glutamine or alanine in the blood stream to the liver and kidney
18
Q
- where is urea produced?
A
- liver
19
Q
what is the fate of NH4+ and why?
A
- NH4+ is toxic
- it is converted to NH3 (urea) in the liver via the urea cycle
20
Q
aminotransferases/transaminases role (2)
A
- equilibrate amino acids among available alpha-keto acids
- permits synthesis of non-essential amino acids, using amino groups from other amino acids and carbon skeletons synthesized in a cell
21
Q
how is nitrogen obtained in humans and what can it be used for? (3)
A
- N must be obtained in the diet as amino acids (proteins)
- we get them from pants/bacteria that can obtain N themselves
- amino N of one amino acid can be used to synthesize another amino acid
22
Q
aminotransferases
A
- catalyze transfer of an alpha-amino group from an alpha-amino acid to an apha-ketoacid
23
Q
aminotransferase reactions (2)
A
- reaction is reversible as there is very little chance in free energy (close to chemical equilibrium)
- direction of rxn controlled by concentration of reactants/products
24
Q
what mechanism does the Ping-Pong use?
A
- Ping-Pong catalytic mechanism: two reactions occurs sequentially, with two sequential substrates taking turns accessing the enzyme active site
25
what are the two sequential aminotransferase reactions?
1. removal of NH3+ created alpha-keto acid
| 2. addition of NH3+ to keto acid creates amino acid
26
why is glutamine, and not glutamate, the main carrier of amino groups on the blood? (2)
- glutamine does not alter pH of the blood due to the lack of negative charge
- negatively charged glutamate will cause blood pH to change
27
describe the glucose-alanine cycle (4)
1. muscles degrade protein into amino acids and amino groups are collected into glutamate by aminotransferase
2. amino group can be transferred to pyruvate to generate alanine and regenerate alpha-ketoglutarate
3. alanine carries amino group to the liver
4. in the liver, alanine is converted back to pyruvate, liberated NH4+ enters the urea cycle
28
what does alanine do for the urea cycle? (2)
- carries NH4+ to the liver
| - 2nd most abundant amino acid in the blood
29
describe the first step of the glucose-alanine cycle (2)
- during strenuous exercise, muscles degrade protein into amino acids for fuel
- this liberates amino groups which are collected into glutamate by aminotransferases
30
describe the second step of the glucose-alanine cycle (2)
- glutamate is converted to glutamine
- amino group can also be transferred to pyruvate to generate alanine (alanine transferase) and regenerate alpha-ketoglutarate
31
describe the fourth step of the glucose-alanine cycle (3)
- in the liver, alanine is converted back to pyruvate
- pyruvate is used to synthesize new glucose and the net effect is to shift the energetic cost of gluconeogenesis to the liver
- liberated NH4+ enters the urea cycle
32
what are the sources of glutamate in the liver? (3)
- glutamine from the blood
- alanine from the blood
- glutamate from intracellular protein catabolism
33
how is glutamates alpha-amino released in the liver?
- oxidative deamination catalyzed by glutamate dehydrogenase to liberate NH4+ and alpha-ketoglutarate
34
oxidative deamination of glutamate (4)
- occurs within the mitochondrial matrix of the liver
- enzyme: glutamate dehydrogenase, only enzyme that ->
- can use either NAD+ or NADP+ as electron acceptor
- ammonia is processed onto urea for excretion
35
how is oxidative deamination regulated? (3)
- controlled by energy balance of the cell
- positively regulated by ADP
- negatively regulated by ATP
36
what can happen to arginine in the urea cycle?
- it can be liberated outside of cycle for other protein needs if necessary
- of this occurs, urea cycle does not go to completion
37
how is the urea cycle regulated? (2)
- allosterically
| - transcriptionally
38
how is the urea cycle regulated transcriptionally?
- carbamoyl phosphate synthetase I (CPS-1) and 4 urea cycle enzymes are up-regulated during starvation (break down of protein occurs) and when there is excess protein
39
how is the urea cycle regulated allosterically? (2)
- CPS-1 is activated by glutamate via N-acetylglutamate
| - N-acetylglutamate is only made when there is enough arginine, glutamate and acetyl-CoA in the cell
40
what are the consequences of deficiencies in the urea cycle enzymes? (2)
- lead to elevated NH4 in blood (hyperammonemia)
| - can not tolerate protein rich diets
41
what is the treatment for urea cycle enzyme deficiences? (2)
- treatment by liver transplantation (usually from parents, but baby will have to take immunosuppressants for the rest of their life)
- dialysis (filter substances out of the blood)
- prodrugs: benzoate or phenylbutyrate is ingested and converted to benzoyl-CoA (removes glycine) or phenylacetyl-CoA (removes glutamine) in body
42
what processes usually occurs in the mitochondria
- energy producing or energy using reactions
43
the administration of these molecules can help treat those with urea cycle enzyme deficiencies (3)
- administration of phenylbutyrate to lower levels of ammonia in blood
- administration of N-acetylglutamate to patients deficient in CPS-1
- administration of arginine to patients deficient in ornithine transcarbamoylase, arginiosuccinate synthetase, or argininosuccinase
44
what other enzymes is PLP used in for amino acid metabolism? (2)
- decarboxylation
| - racemization
45
functions of the TCA cycle (3)
- oxidize acetate to CO2, releasing reducing (NADH/FADH2) equivalents
- intermediates can be drawn out to be used as precursors in various biosynthetic pathways
- 4-5 carbon end products of catabolic pathways (ie. amino acid catabolism) feed into the cycle and serve as fuel
46
ketogenic (2)
- degraded to acetyl-CoA ->-> ketone bodies
| - lysine and leucine are purely ketogenic
47
glucogenic
- degraded to pyruvate ->-> glucose
48
which amino acids are both ketogenic and glucogenic and why? (6)
- tryptophan
- phenylalanine
- tyrosine
- threonine
- isoleucine
- complex skeletons get broken down and enter cycles as different pieces
49
ketone bodies (2)
- acetoacetate, acetone, and beta-hydroxybutyrate
| - synthesized by liver when there is excess of acetyl-CoA and depletion of oxaloacetate
50
what happens when there is an overproduction of ketone bodies?
- acidosis (drop in blood pH)
51
what scenario might cause an excess of acetyl-CoA and depletion of OAA?
- high protein, low carb diet
52
which of the TCA cycle enzymes is membrane bound?
- succinate dehydrogenase (produced FADH2)
53
where does pyruvate enter the TCA cycle and what is generated/consumed? (2)
- oxidized to acetyl-CoA by pyruvate dehydrogenase, generating NADH
- carboxylated to oxaloacetate by pyruvate carboxylase, consuming an ATP
54
how is pyruvate dehydrogenase regulated? (3)
- allosterically inhibited by ATP, acetyl-CoA, NADH, and long-chain FAs
- stimulated by AMP, CoA and NAD+ (which accumulate when too little acetate flows into the TCA cycle)
- activity is regulated by ATP/ADP and NADH/NAD levels
55
how is pyruvate carboxylase regulated? (3)
- inactive in absence of its allosteric activator, acetyl-CoA
- in excess acetyl-CoA, activity is stimulated to produce more oxaloacatate to enable the TCA cycle to use more acetyl-CoA, an anaplerotic reaction
- can be a major reaction in the OAA deficiency situations
56
anaplerotic reaction
- reactions that form intermediates of a metabolic pathway
57
characteristics of enzymes involved in carbon skeleton breakdown (2)
- catalyze chemical rearrangements
| - contain co-factors at their active site
58
what are the main reactions of carbon skeleton breakdown and their co-factors? (3)
- transamination: pyridoxal phosphate (PLP)
- racemization: PLP
- one carbon transfers (most oxidized carbon, intermediate oxidized C, least oxidized C): biotin, tetrahydrofolate, S-adenosylmethionine (SAM)
59
phenylketonuria (PKU) (2)
- accumulation of phenylalanine or derivatives impair normal development of brain
- 8/100,000
60
phenylketonuria treatment
- treated by rigid dietary control (beware of aspartame = dipeptide of Phe and Asp)
61
what causes phenylketonuria?
- defect in the first step of Phe breakdown due to malfunctioning phenylalanine hydroxylase enzyme that catalyzes phenylalanine -> tyrosine
62
what are the ways that an enzyme can be malfunctioning/defected? (3)
- completely missing enzyme
- under-expressed levels of perfectly functional enzyme
- normal expression of complete/partial loss of function enzyme, due to a mutation in the catalytic or allosteric site
63
what is the minor phenylalanine catabolic pathway that is activated in patients with phenylketonuria?
- aminotransferase reaction between phenylalanine and pyruvate to generate phenylpyruvate and alanine
64
what are the compounds that build up in patients with PKU and why is it harmful? (4)
- compounds are toxic and can cause damage to brain cells if left untreated
- phenylpyruvate (ketoacid of phenylalanine)
- phenylacetate
- phenyllactate
65
how is phenylacetate produced from phenylpryruvate?
- addition of H20 and CO2 leaving group
66
alkaptonuria (3)
- 0.4/100,000
- build-up of homogentisate
- homogentisate appears in urine and is deposited in cartilage and elsewhere, making substances appear black (polymerization is black)
67
why does alkaptonuria occur?
- defect in homogentisate 1,2-dioxygenase enzyme that prevents complete breakdown of phenyalanine by inability to convert homogentisate
68
cachexia (3)
- wasting syndrome: weight loss and muscle wasting due to cancer
- tumours produce factors which are secreted and stimulate protein breakdown/autophagy in host cells (in muscle tissue)
- use protein breakdown products to feed the tumours
69
treatment of cachexia
- new drug therapy being developed: normal hormone that stimulates protein anabolism in the muscle
70
what does the breakdown of phenylalanine produce? (2)
- phenylalanine is first broken down to tyrosine
| - tyrosine breakdown produces fumarate and acetoacetyl-CoA (which is broken down into 2 acetyl-CoA)
