Dietary Proteins 2 Flashcards
1
Q
What is the carbon skeleton left from AA metabolism used for?
A
- uses it for fuel
- AAs that are gluconeogenic or glycogenic produce glucose vis GNG
- AAs that are ketogenic produce acetyl CoA and ketone bodies
- some AAs have both gluconeogenic and ketogenic regions
2
Q
Metabolism overview? (4)
A
pics
3
Q
glucogenic AA? (5)
A
- most AAs
- AAs that form pyruvate or intermediates of the TCA cycle
- provide carbon synthesis for glucose
4
Q
ketogenic AA? (5)
A
- a few AAs
- leucine and lysine are exclusively ketogenic
- AAs that are converted to acetyl CoA or acetoacetate can be used to form fatty acids or ketone bodies
5
Q
exclusively ketogenic AAs?
A
- lysine
- leucine
6
Q
glucogenic and ketogenic AAs?
A
- essential: isoleucine, phenylalanine, tryptophan
- nonessential: tyrosine
7
Q
Why so many more glucogenic AAs?
A
- TCA cycle is constantly turning to generate energy
- intermediates of TCA cycle, OAA, have multiple uses
8
Q
starved state?
A
- decreased carbs
- decreased glucose
- decreased insulin
- increased glucagon
- TG stores and protein mobilized for energy from GNG and urea genesis is increased
9
Q
examples of branched chain AA (BCAA)?
A
- valine
- leucine
- isoleucine
- these are essential
10
Q
why can’t the liver use BCAA for energy?
A
-liver does not have BCAA transaminase enzymes
11
Q
where are BCAA metabolized? (7)
A
- enriched in portal circulation and liver, liver does not use BCAA
- BCAA mainly metabolized in peripheral tissues
- all enzymes involved in BCAA metabolism are especially high in muscle
12
Q
3 steps of BCAA metabolism? (8)
A
- BCAA to alpha ketoacids by transamination
- alpha ketoacids to acetyl CoA derivatives by BCAA alpha keto acid dehydrogenase (BCKD)
- derivatives to acetyl CoA (leucine, isoleucine) or succinyl CoA (valine, isoleucine)
13
Q
Maple Syrup urine disease? (8)
A
- deficiency in BCKD (1 in 200,000)
- severe neurological damage, acidosis, sweet smelling urine
- complete enzyme deficiency leads to death within months
- untreated patients with complete enzyme deficiency die within months of birth
- treatments: dietary restriction of valine, leucine, isoleucine, megadose of thiamin
14
Q
BCKD, GDH, PDH? (9)
A
-TPP is cofactor of BCKD, so thiamine dose helps
15
Q
Examples of aromatic AAs?
A
- phenylalanine
- tyrosine
- tryptophan
- all are both glucogenic and ketogenic
16
Q
phenylalanine metabolism? (11)
A
- phenylalanine (essential) goes to tyrosine (nonessential) by Phe hydroxylase, BH4 is coenzyme
- enzyme defect leads to phenylketonuria - tyrosine goes to 4 hydroxyphenyl pyruvic acid by tyrosine transaminase
- enzyme defect leads to tyrosinemia type II - pyruvic acid is converted homogentisic acid by pyruvic acid dehydrogenase
- enzyme defect leads to tyrosinemia type III - homogentisic acid goes to 4 maleylacetoacetic acid by homogentisic acid 1,2 deoxygenase -enzyme defect leads to alkaptonuria
- 4 maleylacetoacetic acid converts to fumarate (glucogenic) or acetoacetate (ketogenic)
- this path can also go to tissue proteins, melanin, or catecholamines
17
Q
what kind of reaction causes phenylalanine to phenylpyruvate?
A
transamination
18
Q
what happens if there is a defect in phenylalanine hydroxylase? (11)
A
- accumulation of phenylalanine
- converts to phenylpyruvate which converts to phenylpyruvate or phenyl lactate (phenylketones)
- phenylketonuria
19
Q
BH4 reactions? (12)
A
- tyrosine synthesis
- catecholamine synthesis
- serotonin synthesis
- BH4 or BH2 deficiency could cause disease
20
Q
Clinical impact of genetic disease? (13)
A
-substrate accumulates, product is deficient
21
Q
genetic disease of phenylalanine summary (14)
A
chart
22
Q
SAM synthesis and one carbon metabolism? (15)
A
- L methionine is converted to S-adenosyl-L-methionine by L-methionine adenosyl transferase, ATP is used
- SAM is very reactive on the methyl group (35 reactions)
- one carbon metabolism:
- the group containing a single carbon atom can be transferred from one compound to another, such as folate (methyl tetrahydrofolate), Vit B12, and SAM
23
Q
Methionine metabolism/remethylation? (17)
A
- SAM transfers methyl group by methyltransferase to become S-adenosyl homocysteine
- hydrolyze it to become homocysteine, adenosine released
- if methionine is inadequate, homocysteine can be resynthesizes to methionine by methionine synthase, Vit B12
- if methionine is adequate, homocysteine becomes cystathione by cystathione beta synthase and Vit B6, and then becomes cysteine
24
Q
Homocystinuria? (18)
A
- lack of Vit B12, B6, or folate
- deficient in methionine synthase or cystathione beta synthase (inherited)
- accumulation of homocysteine, excreted in urine, high in plasma
25
clinical picture of homocystinuria?
- symptoms:
- failure to thrive
- long limbs, tall thin build
- osteoporosis
- mental retardation
- lens dislocation in eye
- thromboembolisms (blood clots, independent risk factor of CVD)
- due to accumulation of homocysteine
- risk for CVD
- similar to marfans syndrome but marfans joints are too loose, homocytinuria joints are too tight
- lab: accumulation of homocysteine, methionine
- genetically due to defect in one carbon metabolism pathways
- cystathione beta synthase deficiency is most common (ireland)
- treatment:
- restriction of dietary methionine
- megadoses of Vit B6, B12, folic acid (boost the homocysteine to methionine reaction)
- betaine
26
homocystinuria due to Vit B12 deficiency?
- causes:
- strict vegans may not consume enough
- pernicious anemia (lack of intrinsic factor to absorb B12)
- other issues affecting stomach or intestine
- lab:
- pernicious anemia (RBC, WBC cannot replicate DNA, become large)
- high homocysteine which increases heart disease risk
- nerve cells damage (demyelination, irreversible)
27
A 5yr. old mentally retarded child is seen by an ophthalmologist for “blurry vision”. Ocular examination demonstrated bilateral lens dislocations, and further workup is significant for osteoporosis and homocystine is high in blood and urine. What kind of disease does he have? Which AA does he has defect in metabolizing?
(A) Hartnup disease: Neutral AA transporter defect
(B) PKU: Phenylalanine metabolism defect
(C) Homocystinuria: Methionine metabolism defect
(D) Cystinuria: COAL transporter defect
C
28
Folate deficiency?
- megaloblastic anemia (due to increased thymine and purine synthesis, less cell proliferation)
- neural tube defects in newborns if mother has folate deficiency during pregnancy
29
Routine screening of infants for genetic diseases? (22)
- PKU (all states)
- MSUD (some states)
- Homcystinuria (all states)
- potential to test 85 disorders with one blood sample by tandem mass spect (40 AA disorders)
30
During a medical rotation, a medical student volunteered for a respiratory physiology examination that determines basal metabolic rate. She followed the protocol for a resting individual in the postabsorptive state. Which of the following AAs would be found in the highest concentration in serum?
(A) Alanine and glutamine
(B) Arginine and ornithine
(C) Glutamate and aspartate
(D) Branched chain AA
(E) Hydrophobic AA
A
- need to transport to liver
- branched chain AA is from food, should be low, it has to be uptake by muscle and peripheral tissues
31
A 5yr. old mentally retarded child is seen by an ophthalmologist for “blurry vision”. Ocular examination demonstrated bilateral lens dislocations, and further workup is significant for osteoporosis and homocystinuria. Genetic test showed the deficiency in cystathionine β-synthase. Serum analysis would most likely show an elevation of which of the following substances?
(A) Cystathionine
(B) Valine
(C) Phenylalanine
(D) Tyrosine
(E) Methionine
E
32
A new test is developed that can nonradioactively “label” compounds in the human body. As a physician with a background in the new field of metabolomics, you assess a 21 yrs. old with classic PKU. The patient is fed phenylalanine with a label in the phenyl ring, and 24-hrs. urine sample is collected. Which of the following compounds would you expect to contain the greatest amount of label in this urine sample?
(A) Tyrosine
(B) Tryptophan
(C) Epinephrine
(D) Phenylketone
(E) Acetate
D
33
A couple of African American descent gives birth to a boy after an otherwise uneventful pregnancy. The child is exceptionally fair-skinned and has almost white hair. Further examination reveals red pupils. A postnatal screen is likely to confirm the deficiency of which of the following enzymes in the child?
(A) Branched chain α-keto acid dehydrogenase
(B) Cystathionine β-synthase
(C) Homogentisate oxidase
(D) Tyrosinase
(E) Phenylalanine hydroxylase
D (albinism)
34
compounds made from AAs? (28)
- histamine
- creatine
- carnitine
- neurotransmitters
35
Histamine synthesis? (29)
- synthesized via decarboxylation of histidine by L-histidine decarboxylase
- PLP is coenzyme
36
Histamine effects?
- released by mast cells as part of an allergic reaction , inflammation
- overreaction leads to asthma and other allergies
- gastric acid secretion
- also released by certain neuronal fibers originating in hypothalamus
37
Creatine synthesis? (30)
- synthesized from glycine and arginine and SAM
1. glycine interacts with arginine in the kidney
2. ornithine is released (urea), Guanidinoacetate is formed
3. guanidinoacetate goes to liver, methylation by SAM (one carbon metabolism) to form creatine
4. creatine is transported to muscle
5. in muscle, creatine kinase (CPK) puts high energy to form creatine phosphate
6. creatine phosphate can create ATP for muscle contraction, intense
7. creatinine is formed, that is excreted in urine
- proportional to muscle mass or kidney function
- low creatinine shows low muscle
- high creatinine, kidney is not functioning well
38
Carnitine synthesis? functions? (31)
- synthesized from lysine and methionine by enzymatic path found in liver and kidney or from diet, especially red meat
- functions:
- carry fat into mitochondria for metabolism
- export from mitochondria of BCAA metabolites
- trap and excretion of acyl group via kidney
39
how neurotransmitter work? (32)
pic
40
Neurotransmitters from AAs? (33)
pic
41
GABA synthesis? (34)
1. start with glutamate
2. glutamate goes to GABA by the enzyme (GAD) glutamic acid decarboxylase (found in GABA nergic neurons)
- coenzyme is PLP
- CO2 is released
42
Serotonin synthesis? (36)
1. hydroxylation of tryptophan (serotonin precursor) to 5 hydroxytryptophan
- requires BH4
2. decarboxylation reaction to serotonin, uses PLP as coenzyme
3. serotonin is a vasoconstrictor and neurotransmitter (well being and relaxation)
4. serotonin further goes to melatonin (hormone for jet lag, sleep issues)
- one carbon metabolism
- serotonin synthesized in pineal gland
43
Serotonin, tryptophan, and sleep?
- serotonin and melatonin induce sleep
- increased amounts of tryptophan cause sleepiness indirectly
- trp competes for transport into brain with other AAs (aromatic, BCAA) on the LAT 1 transporter
- extent of albumin availability also affects availability of trp
- more carb, increases insulin, pushes AA into tissues, allowing more trp into brain, it alleviates its competition
- some types of depression associated with low levels of serotonin (reuptake inhibitors keep serotonin around longer)
44
acetylcholine synthesis? (39)
1. choline can either be synthesized or derived from diet
2. one carbon metabolism using SAM
3. choline is used to make glycine
4. memory and motor control and major neurotransmitter in parasympathetic nervous system
5. acetylcholinesterase breaks down acetylcholine
45
Function of acetylcholine? (40)
- muscle contraction
- neurotransmitter in parasympathetic system
- help digest, slow heart rate
46
A 75 yrs. old Man experiences severe chest pain radiating down his left arm. He calls 911 and is transferred to the ER where an ECG indicates that he is having a myocardial infarction. Serum levels of cardiac creatine kinase are elevated. What is biological role of the product of this enzyme?
(A) An intracellular antioxidant
(B) A storage form of high-energy phosphate
(C) An inhibitory neurotransmitter
(D) Stimulates the release of hydrochloric acid from the stomach
(E) A bactericidal product produced by macrophages
B
