L18: Protein Metabolism Flashcards
(105 cards)
1
Q
What are the key enzymes involved in protein digestion?
A
Pepsin, Trypsin, Chymotrypsin
These enzymes break down dietary proteins into smaller peptides and amino acids.
2
Q
What is nitrogen balance?
A
The difference between entries and exits from the amino acid pool
It reflects the availability of amino acids for protein synthesis.
3
Q
Define protein turnover.
A
The balance between degradation and synthesis of endogenous proteins
This process ensures a constant supply of functional proteins in the body.
4
Q
What happens when there is a lack of esential AA?
A
endrogenous (already in us) protein degredation -> essential AA.
5
Q
2 enzymes in protein degredation
A
Ubiquitine-proteasome (ATP needed!)
Lysosomes
6
Q
What triggers the digestion of dietary proteins in the stomach?
A
Low pH (acidity)
This acidity denatures proteins, making them accessible for enzymatic breakdown.
7
Q
What denaturizes proteins
A
Pepsin
8
Q
Where does the digestion of dietary proteins begin?
A
In the stomach
Here, pepsin initiates the breakdown of proteins into polypeptide & AA.
9
Q
What happens to polypeptides in the small intestine?
A
They are broken down into amino acids
And eventually A.A. are absorbed in small intestine
10
Q
Importance of bile in digestion of proteins
A
Neutralizes pH by sodium
bicarbonate in the bile
11
Q
What enzymes does the pancreas release in protein digestion?
A
Trypsin, Chymotripsin, carboxypeptidase elastase
12
Q
What enzymes are released by the small intestine during protein digestion?
A
Amino-peptidase, Di/Tri-peptidase
For digestion
13
Q
What is the role of zymogens in digestion?
A
They are inactive forms of digestive enzymes that require activation
Activation occurs through proteolytic cleavage (Catalysis, autocatalysis)
14
Q
Fill in the blank: Diseases relating to the digestion of dietary proteins usually relate to damages to the _______.
A
small intestine
Conditions like Celiac disease or Crohn’s disease can affect protein digestion.
15
Q
What is celiac disease?
A
Gluten
Autoimmune disorder -> damage small intestine
16
Q
Malabsorption syndromes
A
Protein intolerance/allergies
Chron’s, cystic fibrosis
17
Q
What are common symptoms of protein digestion disorders?
A
Troubles of digestion and protein/lipids in feces
These symptoms can indicate malabsorption issues.
18
Q
What are Essential Amino Acids?
A
Amino Acids that cannot be synthesized from other Amino Acids or metabolic intermediates and must be supplied by the diet (e.g., Phenylalanine, Valine, Leucine).
19
Q
What are Nonessential Amino Acids?
A
Amino Acids that can be synthesized from other Amino Acids or metabolic intermediates (e.g., Alanine, Asparagine, Glutamate, Aspartate, Serine).
20
Q
What does ‘conditionally nonessential’ mean?
A
Amino Acids that must be supplied by the diet only in certain situations such as malnutrition, illness, or for preterm infants (e.g., Glutamine, Glycine, Tyrosine, Cysteine, Tyrosine).
21
Q
How are Nonessential Amino Acids synthesized from α-ketoacids?
A
They are synthesized by enzymes called Transaminases
22
Q
What is glutamate synthesized from
A
alpha-ketoglutarate
A.A. transaminase (requires vit b6)
23
Q
What is aspartate synthesized from
A
oxaloacetate + glutamate (AST)
24
Q
What is serine synthesized from
A
Pyruvate from glycolysis
25
What is the role of Aspartate Transaminase (AST)?
Catalyzes the synthesis of Glutamate from α-ketoglutarate and Asparate from oxaloacetate.
**Catabolism**
26
What is synthesized from enzymes modifying existing AA?
Glutamin from glutamate
Tyrosine from phenylalanine
Aspartate from Asparagine
27
What is Neutral Nitrogen Balance?
Entries = Exit, indicating normal nutrition.
28
What is Positive Nitrogen Balance?
Entries > Exit, examples include growth, body building, tissue repair, pregnancy.
29
What is Negative Nitrogen Balance?
Exit > Entries, examples include fasting, tissue injuries, wasting diseases, malnutrition.
30
What is Amino Acid Catabolism?
The process where amino acids are used as metabolic fuel -> intermediates of glucose or lipid metabolism, and detoxifying amine groups as Urea.
31
When does Amino Acid Catabolism occur?
When protein intake exceeds needs
skeletal muscle proteins are used for energy (intense exercise / starvation)
diet lacks essential amino acids.
32
What are the two pathways for the Amine group and Carbon skeleton of Amino Acids?
Amine groups -> Urea (urea cycle)
Carbon skeletons -> intermediates of glucose or lipid metabolism.
33
What is the central organ of Amino Acid Catabolism?
**LIVER**
34
Fill in the blank: Amino acids are catabolized when too much OR too little _______ is consumed.
protein
35
True or False: Degradation of skeletal muscle is an abnormal response to injury/infections.
False, it is normal
36
What is the main risk associated with the catabolic degradation of Amino Acids?
Formation of Ammonia (NH3)
Death
## Footnote
Ammonia is highly toxic for the Central Nervous System.
37
What molecule is formed when Amine group is combined with Ammonia in the detoxification process?
Urea
## Footnote
Urea is excreted in urine.
38
What are the two key reactions in the catabolism of Amino Acids?
* Transamination
* Oxidative Deamination
39
Metabolic intermediates of transamination
alpha-keoglutarate
Oxaloacetate
Pyruvate
40
Where does transamination typically start?
In peripheral tissues, such as the muscle
41
What is transferred to an α-ketoacid during transamination?
The Amine group (-NH2)
42
Show reaction that transamination catalyzes
AA1 + alpha-ketoacid 1 -> Glutamate + alpha-ketoacid 2
43
What is the role of Glutamate in Amino Acid catabolism?
Amine groups are funneled to glutamate
44
Which vitamin is required for the function of all transaminases?
Vitamin B6
45
What are the two Amino Acids that Glutamate is transformed into for transport to the liver?
* Glutamine
* Alanine
46
What happens once Alanine and glutamine reach the liver?
Transformed back into glutamate
47
What enzyme transforms Glutamine into Glutamate?
Whats produced from the reaction?
Glutaminase
reaction produces Ammonia (NH3)
48
What does Alanine Transaminase (ALT) do?
Transfers the Amine group of Alanine to Glutamate + vise versa
49
What is a significant clinical marker of liver damage?
Detection of ALT in the blood
50
How does Glutamate release its Amine group in the liver?
* Oxidative Deamination by Glutamate Dehydrogenase
* Transamination by Aspartate Transaminase (AST)
51
What is released during oxidative deamination of Glutamate?
Ammonia (NH3)
52
What does Aspartate Transaminase (AST) transfer?
The Amine group to Aspartate
53
Is AST a specific marker for liver damage?
No, it is less specific than ALT as it is found in muscles and other organs.
54
What are the two key components of the Urea cycle? Why?
* Ammonia
* Aspartate
They each provide one of the nitrogen to the urea
55
What is the Urea cycle?
A series of reactions leading to the transfer of Nitrogen atoms of Ammonia and the Amine group of Aspartate to Urea.
## Footnote
The Urea cycle takes place in the liver.
56
Where does the Urea cycle take place?
**LIVER**
## Footnote
The liver is the primary site for the Urea cycle, processing nitrogen waste.
57
What enzyme does this:
ammonia + CO2 -> Carbamoyl Phosphate
Carbamoyl Phosphate Synthetase I (CPS I).
## Footnote
This step is the **limiting** step of the Urea cycle.
58
What is the role of N-acetyl Glutamate (NAG) in the Urea cycle?
It acts as an allosteric regulator for CPS I (activates or increases it)
## Footnote
NAG synthesis is regulated by Arginine.
59
How does the accumulation of Arginine affect CPS I activity?
It leads to increased CPS I activity.
## Footnote
Arginine is a precursor to Urea.
60
Where do the 2 key reactions of amine group elimination take place?
Liver mitochondria
61
What reaction does Ornithine Transcarbamylase (OTC) catalyze?
Carbamoyl Phosphate + Ornithine -> Citrulline
## Footnote
OTC is the most common genetic defect related to Urea cycle pathologies.
62
Importance of OTC enzyme
Most common genetic defect relating to urea cycle
63
What happens to Citrulline after it is formed?
It passes into the cytosol of liver cells.
## Footnote
Citrulline contains the Nitrogen atom of the original Ammonia molecule.
64
What is formed from Aspartate + Citrulline?
Argininosuccinate.
## Footnote
Argininosuccinate is a precursor to Arginine and contains two amine groups.
65
What are the two products of Argininosuccinate transformation?
Transforms to Arginine -> Urea and Ornithine
66
What does Urea contain in terms of amine groups?
Two amine groups (-NH2).
## Footnote
One amine group comes from Ammonia and the other from Aspartate.
67
How is Ornithine related to the Urea cycle?
It goes back to the mitochondria to synthesize Citrulline.
## Footnote
This recycling process is why it is called the Urea cycle.
68
What does the Urea cycle consume and generate?
Consumes Oxaloacetate
Generates Fumarate
69
Does the Urea cycle consume ATP?
Yes, several steps in the Urea cycle consume ATP.
## Footnote
ATP is required for the energy-intensive reactions in the cycle.
70
Where is Urea produced and where does it go?
Liver -> relased in bloodstream -> kidneys -> urine
71
What is the purpose of measuring Urea levels in the blood?
To detect and diagnose kidney dysfunction
72
What is Hyperammonemia?
Elevated levels of Ammonia in the blood & body
Ammonia = damage to CNS
73
What are common symptoms of Hyperammonemia?
* Tremors
* Slurring of speech
* Drowsiness
* Vomiting
* Edema
* Blurred vision
* Coma
* Death
74
What is Acquired Hyperammonemia? What causes it?
Liver damage due to viral infection or substances damaging the liver
Defective detoxification of ammonia
75
What is a common cause of Congenital Hyperammonemia?
Rare Genetic disorders leading to defects in enzymes of the Urea Cycle
Usually in newborns -> brain damage/mental retardation
76
Which enzyme is most commonly defective in Congenital Hyperammonemia?
Ornithine Transcarbamylase (OTC)
X-linked disorder
77
What treatment options exist for Hyperammonemia?
* Diet restriction
* Hemodialysis
* Arginine
* Molecules binding to Glutamate (Phenylbutyrate/Phenylacetate)
78
What is the relationship between amino acids and their carbon skeletons?
They can be modified to join glucose or lipid metabolism
79
What are Glucogenic Amino Acids transformed into?
Intermediates of glucose metabolism
* Pyruvate
* Intermediates of the TCA cycle (α-ketoglutarate, fumarate, oxaloacetate)
ex: glutamate, alanine
80
What are Ketogenic Amino Acids transformed into?
Intermediates of lipid metabolism
* Acetyl CoA
* Oxaloacetate
ex: leucone, lysine
81
Can amino acids be both glucogenic and ketogenic?
Yes, dif pathways
Ex: Phenylalanine and Tyrosine
82
What does a deficiency in an enzyme related to Amino Acid Catabolism lead to? Treatment?
| In terms of carbon skeleton
Toxic accumulation of an Amino Acid or an intermediary metabolite
Treatment: remove AA from diet and supplement
83
What is Phenylalanine Ketonuria (PKU)?
Autosomal recessive
defect in Phenylalanine hydroxylase (phenylalanine -> tyrosine) leading to accumulation of neurotoxic derivatives of phenylalanine
Leaks in urine -> musty odor
Can lead to mental impairment
84
Describe what a mutation in OTC is
X-linked
Congenital hyerammonemia
Lethargy, mental impairment
85
Treatment of OTC disease
Limit protein from food, hemodialysis, give arginine (stimulates CPS1) + molecules binding to Glutamate
to help its excretion (Phenylbutyrate/Phenylacetate).
86
What is the treatment for Phenylalanine Ketonuria (PKU)?
* Strict dietary restrictions
* Use of synthetic food without Phenylalanine
* Supplementation with Tyrosine
87
What is Maple Syrup Urine Disease (MSUD)?
Autosomal recessive
Deficiency in enzymes processing Branched Chain Amino Acids (BCAAs) (**BC ketoacid dehydrogenase complex**) -> toxic extra BCAAs and alpha-ketoacids -> leak in urine
Detected @ pre/neonatal screening
Mayple syrup smell from **Isoleucine** in urine
88
What are the consequences of Maple Syrup Urine Disease (MSUD)?
* Feeding problems
* Vomiting
* Neurological problems
* Coma
* Death
* Ketoacidosis
89
What is the treatment for Maple Syrup Urine Disease (MSUD)?
* Strict dietary restrictions
* Use of synthetic food without BCAAs
* Supplementation with BCAAs at low levels
90
What are the key roles of Nucleotides?
* Energy: ATP is a nucleotide
* Precursors to RNA and DNA (purines, pyrimidines)
* Components of important coenzymes: NADH, NADPH, FADH2, CoA
* Cellular communication & regulation: cAMP, GTP
## Footnote
Nucleotides play diverse roles in cellular metabolism and functions.
91
Which amino acids are essential for the synthesis of Nucleotides?
* Glycine
* Glutamine
* Aspartate
## Footnote
These amino acids are critical precursors in nucleotide metabolism.
92
What is Severe Combined Immunodeficiency Disease (SCID) related to?
| Regarding nucleotide pathology
Enzymatic deficiency leads to the absence of B and T cells
**ADA deficiency -> extra dATP**
## Footnote
Treatments include enzyme replacement therapy, antibiotics, bone marrow transplant, and gene therapy.
93
What causes Gout in relation to Nucleotide metabolism?
Deficiency in the **metabolism of nucleotides** leads to the accumulation of **Urate** -> inflammatory response, kidney damage, and nephropathy.
AKA: hyperuricemia
## Footnote
Treatments include drugs that block Urate synthesis and anti-inflammatory medications.
94
What are the two essential functions of Heme?
* Assembled with Globins to form **Hemoglobin**
* Cofactor for several enzymes in the liver (e.g., Cytochrome P450)
## Footnote
Heme is crucial for oxygen transport and detoxification processes.
95
Where is Heme synthesized?
* Bone marrow (85% of total production)
* Liver (15% of total production)
## Footnote
The synthesis occurs primarily in red blood cell precursors and hepatocytes.
96
What is the precursor for Heme?
Glycine
## Footnote
Four Glycines are combined and transformed by ALAS enzymes to synthesize Heme.
97
What is Creatine formed from?
Glycine + Arginine in the liver and kidneys.
## Footnote
Creatine serves as a backup energy supply in muscles.
98
Where does creatine travel to?
Skeletal and cardiac muscle
| It is an important clinical marker for myocardial infarction.
99
What role does Creatine Kinase play?
Creatine is phosphorylated by Creatine Kinase to creatinine
regenerate ATP
100
What happens to Creatine and Creatine Phosphate?
They are degraded into Creatinine, which levels in urine can estimate muscle mass.
## Footnote
Elevated Creatinine in blood indicates kidney malfunction.
101
What are the derivatives of Tyrosine?
* Melanin
* Catecholamines (Dopamine, Norepinephrine, Epinephrine)
## Footnote
Tyrosine is crucial for various biological functions including UV protection and neurotransmission.
102
What is the role of Melanin?
Responsible for UV protection.
## Footnote
Defects in Tyrosine metabolism can lead to **Albinism**.
103
What are catecholamines? Clinical relevance?
Neurotransmitters (dope, norepi)
Parkinsons treated w/ dopamine increase
epi & norepi -> fight or flight hormones
104
What is S-Adenosyl Methionine (SAM) synthesized from?
Methionine + ATP
involving vitamin B12 and Folate
Potential anti-caner drug
## Footnote
Homocysteine (Hcy) is an intermediate and a marker in **cardiovascular diseases.**
105
Why is SAM important?
Universal donor of methyl group (-CH3) for methylases.
## Footnote
SAM regulates key processes such as **DNA methylation.**
