Amino Acid Metabolism Flashcards
1
Q
Amino group (NH2) of aa metabolism
A
Liver–>urea all other tissues–>glutamate–(+NH2)–>glutamine
2
Q
Carbon skeleton of aa metabolism 3 ways
A
- glucogenic aa–> glucose synthesis 2. ketogenic aa–>ketone bodies: β hydroxy butyrate acetoacetate acetone (gas) 3. energy least of the three
3
Q
digestion of dietary proteins
A
- pepsin released by chief cells of the stomach 2a. apical membrane bound peptidases released by small intestine 2b. exocrine pancreatic enzymes trypsin chymotrypsin aminopeptidases elastases –>small peptides (80%) and free aa (20%) in the intestinal lumen
4
Q
peptide absorption in enterocytes
A
small peptides are transported through the PEPT1 active transporter–peptidases in enterocyte–>aa–>transported into the blood using aa transporters
PEPT1 is a cotransporter of small peptides and protons into the enterocyte
5
Q
free aa absorption in enterocytes
A
free aa enter are transported into the enterocyte using aa transporters
6
Q
PEPT1 transport driving force
A
active force driven by electrochemical proton gradient more protons in the lumen/ less in the enterocyte. more acidic lumen pH at the center of the lumen 7.0-7.4 pH near apical border of enterocyte 5.5-6.0
7
Q
Disease: Hartnup’s Disease
A
- genetic defect in the neutral aa transporters in intestine (apical membrane) and kidney (apical membrane)
- results/symptoms: cystinuria, pellagra-like symptoms (b/c Trp–>niacin), neutral aa in the urine, neurological problems
- test: give tryptophan orally; no free trp can enter enter intestinal cells;
- tryptophan also can’t enter kidney–>excreted in urine
- treatment: give tryptophan in the form of a small peptide: Gly-Trp, Trp-Trp, Lys-Trp; these enter through PEPT1
- benign in this country
- applies to all neutral aa:
8
Q
Disease: Cystinuria
A
- genetic defect in basic aa (Lys, Arg) and cystine transporters in the intestine and kidney
- no malabsorption b/c these aa can be digested as peptides such as Lys-Leu
-
results/symptoms: Lys, Arg, and Cystine in the urine
- excess cystine in kidney(crystallization–>kidney stones
- treatment: drink 8-10 glasses of water a day or drink more beer (increases water reabsorption)
9
Q
Marasmus Disease
A
- Protein and energy (carbohydrates and fats) deficiency in diet–starvation
- results/symptoms: stunted growth, loss of adipose tissue, muscle wasting, generalized wasting of protein mass, and NO EDEMA
- low plasma insulin, high plasma glucagon, high plasma glucocorticoids (cortisol)–>increased gluconeogenesis from glycerol (increased lipolysis) and glucogenic aa (increased muscle protein breakdown) to maintain blood glucose levels to support the brain.
- increased fatty acid mobilization from adipose tissue to liver–> increased production of ketone bodies–
- ketone bodies can serve as substrates for energy production in the brain
10
Q
Kwashiorkor Disease
A
- Protein deficiency in diet; energy intake (carbohydrates and fat) adequate
- child eats more carbs to compensate for protein deficiency
- High plasma insulin, low plasma glucagon, low plasma gluccorticoid (cortisol)–>Lipolysis in adipose tissue is inhibited, fatty acid synthesis in liver is enhanced (fatty liver), mobilization of aa from muscle is inhibited
- Decreased levels of aa in the blood–>decreased protein synthesis in liver–>hypoalbuminemia–>edema (water accumulation in extracellular fluid in tissues)
- results/symptoms: growth failure, edema, hypoalbuminemia, and fatty liver
- eats more carbs–>excess glucose–>fats–>deposited in liver (abdominal protrusion and shiny skin)
11
Q
Kwashiokor Disease and Marasmus Disease
A
table
12
Q
AA carbon skeleton metabolism
Glucogenic aa can be converted into:
A
- pyruvate
- alpha Ketoglutarate
- Succinyl CoA
- Fumarate
- Oxaloacetate
13
Q
Glucogenic aa converted to pyruvate
A
- Glycine
- Alanine
- Serine
- Cysteine
- Threonine
- Tryptophan
14
Q
Glucogenic aa converted to alpha Ketoglutarate
A
- Glutamate
- Glutamine
- Histidine
- Arginine
- Proline
15
Q
Glucogenic aa converted to Succinyl CoA
A
- Isoleucine
- Methionine
- Threonine
- Valine
16
Q
Glucogenic aa converted to Fumarate
A
- Phenylalanine
- Tyrosine
- Aspartate
17
Q
Glucogenic aa converted to Oxaloacetate
A
- Aspartate
- Asparagine
18
Q
AA carbon skeleton metabolism
Ketogenic aa can be converted to
A
- ketogenic aa–>acetyl CoA–>
- fat
- glucose
- ketone bodies:
- ß hydroxy butyrate
- acetoacetate
- acetone (gas)
19
Q
Ketogenic aa
A
- Leucine
- Lysine
- Isoleucine
- Phenylalanine
- Tyrosine
- Tryptophan
bold=purely ketogenic aa; do not overlap with glucogenic
20
Q
Glucogenic and Ketogenic aa
A
- Isoleucine
- Phenylalanine
- Tyrosine
- Tryptophan
21
Q
Branched chain aa
A
- Valine–>Propionyl CoA
- Isoleucine–>Propionyl CoA or Acetyl CoA
- Leucine–>Acetyl CoA
22
Q
Brached chain aa metabolism
A
- Rxn 1: Transamination–>alpha keto acid
- aa + alpha ketoglutarate–>keto acid + glutamate
- CHNH2 group–>C=O
- Rxn 2: Brached chain alpha ketoacid dehydrogenase
- needs the 5 vitamins: Thiamine, Niacin, Lipoic acid, pantathenoic acid, riboflavin
- COOH group–>CoA; CO2 released
23
Q
Branched chain aa metabolism:
Valine and Isoleucine
A
- Valine–>propionyl CoA; Isoleucine–>propionyl CoA
- propionyl CoA–(propionyl CoA carboxylase) needs biotin–>methyl malonyl CoA
- methyl malonyl CoA–(methyl malonyl CoA mutase) needs B12–>Succinyl CoA
24
Q
Maple Syrup Urine Disease
A
- Genetic defect in the Branched chain alpha Ketoacid dehydrogenase enzyme in branched chain aa metabolism
- defect in Isoleucine, Leucine, and Valine metabolism
- ketoacids–X–>CoA derivatives
- result: ketoacid accumulation in blood and excreted in urine
- symptoms: ketoacidosis, protein intolerance, mental retardation, growth retardation, early death
- aka Burnt Sugar Disease
- Isoleucine, Leucine, and Valine important for brain function (essential aa)
- treatment: limit Isoleucine, Leucine, & Valine in diet
25
Methyl Malonyl CoA Mutase Defect
1. In branched aa metabolism; requires B12
2. CoA derivates--X--\>succinyl CoA
3. accumulation of methyl malonyl CoA--\>increased methyl malonic acid in blood;
* also increased propionic acid in blood
* also increased corresponding aa keto acid in blood
4. **results/symptoms: methylmalonyl aciduria, ketoacidosis (Val and Ile only), mental retardation, protein intolerance**
5. **Treatment: limit Valine and Isoleucine in diet **
26
B12 deficiency in branched chain aa metabolism
1. synth. by animal and ingested in diet by humans; pts of **vegan diet**
2. B12 needed for methylmalonyl CoA mutase--\>succinyl CoA
3. accumulation of methylmalonyl CoA in **blood and urine**
4. **results/symptoms: methylmalonyl aciduria, megaloblastic anemia (macrocytic anemia), anemica, Leucopenia, thrombocytopenia**
5. **pamcytopenia: all blood cells are low**
27
Phenylketonuria
1. genetic defect of enzyme Phenylalanine hydroxylase
2. Phe--X--\>Tyr--\>Melanin
3. addition of OH group; H2O produced; H2 in water comes from THB
4. results: increased Phe; decreased Tyr
5. Normally, Phe (essential) and Tyr (non essential b/c it can be synth. from Phe)
6. PKU: Phe (essential) & Tyr (essential)
7. PKU, Phe--\>phenyl pyruvate,(keto acid w/ phenyl group), phenyl acetate, and phenyl lactate--\>excreted in urine
8. Phenyl acetate has mousy/musty smell
9. results/symptoms: increased Phe in urine, phenyl derivates in urine, musty/mousy urine smell; mental retardation in untreated pt.; blond hair, blue eyes, fair skin
10. treatment: diet with reduced and limited Phe; Tyr supplement; must be given within 3 weeks of births
28
Types of PKU
1. **Classical PKU: Phe hydroxylase mutated; respond to diet therapy**
2. **Atypical PKU**: normal Phe hydroxylase; **THB deficiency**; don't respond to diet therapy with limit Phe and Tyr supp;
3. THB needed for:
* Phe--(THB)--\>Tyr--(THB)--\>DOPA--\>dopamine--\>norepinephrine
* Trp--(THB)--\>5-OH Trp--\>Serotonin
4. **results: Increased Phe, decreased Tyrosine, dopamine, norepinephrine, serotinin**
5. **symptoms: mental retardation**
6. **Treatment:Limit Phe, Tyr supplement, and supply THB**
7. Maternal PKU
29
Maternal PKU
1. Mother with PKU received diet therapy while undergoing brain development;
2. no diet therapy during pregnancy
3. child is heterozygous for Phe Hydroxylase +/-
4. Phe passed to fetus through placenta
5. fetus develops PKU symptoms even when exposed to Phe even though it is PKU heterozygous +/-
6. results/symptoms: delayed brain development, growth retardation, PKU symptoms
30
Alkaptonuria
1. Disease of Tyrosine metabolism--**genetic defect of HGA oxidase**
2. Tyrosine-------\>Homogentisic acid (HGA)--X--(HGA oxidase)--\>4-maleylacetoacetate
3. results: increased HGA in blood and excreted in urine--**acidic urine**
* acidic urine exposed to sunlight or O2--\>**turns black**
4. no complications at young age;
* HGA accumulates in soft tissues and connective tissue--at age 40-50--\>**severe degenerative arthritis**
* HGA precipitates bluish-gray in soft tissues (nails, sclera, etc.)--**oronosis**
* **cardiac problems** b/c HGA accumulates in cardiac valve
31
Tyrosine metabolism
1. Phe--\>Tyr--(Tyr hydroxylase)--\>DOPA--\>dopamine--\>norepinephrine
2. Phe--\>Tyr--(Tyrosinase)--\>DOPA--\>DOPA quinone--\>melanin
3. Tyr-------\>HGA--\>4-maleylacetoacetate
32
Albinism
1. Tyrosine metabolism; genetic defect in tyrosinase
2. Phe--\>Tyr--X--(Tyrosinase)--\>DOPA--X--(Tyrosinase)--\>DOPA quinone--\>melanin
3. no PKU symptoms; melanin decreases--\>photosensitivity (sun burn easily)
33
Methionine Metabolism
1. Methionine--\>S-adenosyl methionine--(X--\>XCH3)--\>S-adenosyl homocystein--\>homocysteine
* Homocysteine--(B12CH3\*\*\*--\>B12)--\>Methionine. enzyme: **methionine synthase; requires: B12 and THF**
* \*\*know the regenration with THF
* Homocysteine--\>Cystathionine--\>Cysteine. enzyme: **Cystathionine Beta Synthase; required B6**
* Methyl THF--\>THF enzyme: methionine synthase
* THF--(Ser--\>Gly)--\>methylene THF--(**enzyme: methylene THF reductase**)--\>methyl THF
34
Enzymes to regulate homocysteine
* Homocystein = bad! two enzymes to keep it in check
1. methionine synthase
* requires B12 and THF
2. cystathionine beta synthase
* requires B6
* Hcy--SH homocysteine
* Hcy--S--S--Hcy homocystine
35
Hyperhomocysteinemia
1. =homocysteinuria; increased homocysteine
2. Two ways:
1. defect in methionine synthase
* increased homocysteine; decreased methionine; increased cysteine
2. defect in cystathionine beta synthase
* increased homocysteine; increased methionine; decreasedcysteine
36
B12 deficiencey in aa metabolism
1. B12 needed for methylmalonyl CoA mutase
2. B12 needed for methionine synthase
* increased homocysteine; decreased methionine; increased cysteine
* same with folic acid deficiency
3. Only two enzymes require B12 so this allows to differentiate between the causes of homocysteine: defect in methionine synthase or defect in cystothionine beta synthase.
* only methionine synthase requires B12...and folic acid; cystathionine doesn't
37
B12 deficiency vs. Folic Acid deficiency
38
Five causes of homocysteinuria
1. defect in methionine synthase
2. Cystothionine beta synthase
3. B12 deficiency (MS)
4. Folic acid deficiency (MS)
5. B6 deficiency (CBS)
39
Homocysteinuria symptoms
1. Collagen contains a lot S--S; if increased H-SH breaks S--S
2. Effects:
1. **Bone--Osteoporosis**
2. **Vasculature--clotting, thrombosis**
1. cerebral--\>mini strokes--\>**mental retardation**
2. coronary--\>**heart attack**
3. peripheral--\>**ischemia**
3. Ligaments--\>eye--\>dislocation of lens--\>**ectopia lentis**--\>**glaucoma** (change in pressure in eye)
40
One carbon transfers
1. four forms: methyl (CH3), formyl (CHO), methylene (CH2), methenyl (CH=CH)
2. CH3 methyl can be transferred by three carriers:
* SAM--most prevalent
* CH3THF (only for MS)
* CH3B12 (only for MS)
3. all four one-carbon groups can be transferred by THF. THF is most versatile
