Biochem - E4 Flashcards
1
Q
Aa –> acetyl coA
A
Leucine, lysine
Phenylalanine, tyrosine, tryptophan
2
Q
Aa –> pyruvate
A
alanine, cysteine, glycine, serine, threonine
3
Q
Aa –> oxaloacetate
A
asparagine –> aspartate –> oxaloacetate.
4
Q
Aa –> fumerate
A
aspartate, phenylalanine, tyrosine
5
Q
Aa –> succinyl CoA
A
Isoleucine, methionine, threonine, valine
6
Q
Aa –> fumarate and acetoacetate
A
Phenylalanine, tyrosine
7
Q
Branched amino acid breakdown
A
The Breakdown of Branched Chain Amino Acids (Valine, Isoleucine, Leucine) is via aminotransfer to form keto acids, and then the action of a BCAA dehydrogenase
Defective dehydrogenase –> maple syrup urine disease
- muscle prefers branched, liver has NO branched-chain aminotransferase
8
Q
Periportal region of liver
A
Converts ammonia to urea
9
Q
Perivenous region of liver
A
Converts ammonia to glutamine
10
Q
Some glycogenic amino acids are interconvert with a-Ketoglutarate (via glutamic gamma-semialdehyde)
A
Arginine *and ornithine Proline Glutamine Glutamate --> alpha-ketoglutarate
11
Q
Propionyl-CoA –> succinyl-CoA requires
A
biotin and vitamin B12
12
Q
methylmalonate buildup –> dx of
A
methylmalonyl CoA MUTASE defect (due to lack of vitamin B12, or prob w/ absorption w/ intrinsic factor, or prob with conversion to adenosyl form of vitamin B12)
13
Q
Adenosylcobalamine
A
Vitamin B12 in the adenosyl form –> needed for catabolism of valine, isoleucine, methionine. (all go to propionyl CoA –> succinyl CoA)
Vitamin form would be -OH or -CN
14
Q
Oxaloacetate pathway
A
Asparagine –> aspartate –> oxaloacetate ( –> PEP –> glucose)
15
Q
Phenylalanine –> tyrosine rxn
A
Via phenylalanine hydroxylase and tetrahydrobiopterin
16
Q
dihydrobiopterin –> tetrahydrobiopterin
A
dihydrobiopterin reductase
17
Q
PKU is due to which deficiency
A
Via phenylalanine hydroxylase deficiency OR due to dihydrobiopterin reductase deficiency
18
Q
Which aa makes nitric oxide
A
arginine * an essential aa
19
Q
Tyrosine –> dopa
A
Via tyrosine hydroxylase and tetrahydrobiopterin
20
Q
Tyrosine –> Dopa —?—> dopamine
A
Via decarboxylase and PLP
21
Q
? –> thyroxine (T4)
A
Tyrosine + iodine (on thyroglobulin protein) –> thyroxine (thyroid peroxidase)
22
Q
? –> melanin
A
tyrosine –> melanin. Via tyrosinase (tyrosine-3-monooxygenase)
23
Q
Albinism
A
tyrosine –> melanin. Via tyrosinase (tyrosine-3-monooxygenase) (defective –> albinism)
24
Q
Rxns requiring PLP (pyrodoxial phosphate)
A
Aminotransferase rxn –> exchange between keto/amino forms of aa
THF + serine –> glycine + methylene form THF
Dopa –> Dopamine
Homocysteine –> cystathione (–> cysteine)
25
Gout
Increased uric acid in blood
| Deficiency in HGPRT, or PRPP synthase, or G-6-Pase deficiency (increased PPS, xs R-5-P)
26
Tx for gout
Allipurinol
^ hypoxanthine analogue, competitive inhibitor of xanthine oxidase.
hypoxanthine and xanthine accumulate --> more soluble than uric acid
27
Lesch-Nyhan Syndrome
lack functional HGPRT (increased uric acid in serum)
- -> self-mutilation, mental illness and gout like sx
- Marked increase in the rate of purine biosynthesis by the de novo pathway
28
SCID
ADA (adenosine deaminase deficiency)
29
Sulfonamides
Antibacterial agents. Resemble p-aminobenzoic acid and inhibit synthesis of folate in bacteria, thus unable to form purines and thus their duplication is blocked. Humans not affected by sulfonamides (bc dietary folate).
30
6-mercaptopurine
analogue of hypoxanthine, rely on activation by salvage pathway
After salvage, a potent competitive inhibitor of IMP in the pathways for AMP and GMP biosynthesis.
Once combined with PRPP it acts as a competitive inhibitor of IMP in the pathways for AMP and GMP biosynthesis.
Tx for acute leukemia
31
Gastric glands
secrete Hcl and pepsinogen
32
Pepsinogen
propeptide of pepsin binds at high pH (inside cells, for example)
Pepsin --> active at low pH
33
Pancreas
```
Secretes bicarbonate & neutralizes stomach contents (pH increases to 7 in duodenum)
Secretes zymogens (trypsinogen, chymotrypsinogen, proelastase, procarboxypeptidase) through pancreatic duct
```
34
CCK
secreted by cells in the duodenum and stimulates the release of bile into the intestine and the secretion of enzymes by the pancreas.
35
enteropeptidase
secreted by cells of SI, initiates conversion of trypsinogen --> trypsin
36
Enzymes of small intestine
trypsin
chymotrypsin
elastase
carboxypeptidase
dipeptase
aminopeptidase
37
Endopeptidases
- Break proteins at peptide bonds, producing short peptides
| - trypsin, chymotrypsin, elastase, pepsin
38
Exopeptidase
- Break peptide bonds at N/C regions, producing aa
| - carboxypeptidases
39
Trypsin
In SI
| Binds + aa
40
Villi of SI release...
enteropeptidase and also bicarbonate
41
Hereditary pancreatitis
mutation in trypsin reduces binding to its inhibitor --> overactive trypsin.
Damages pancreatic tissue and triggers immune response --> inflammation of pancreas
(*or mutation that makes trypsinogen convert too readily to the active trypsin form, or mutations in the inhibitor itself)
42
Intestinal cell transporters
aa go in through Na linked transporters specific for aa (cystine and lysine go in through same transporter)
aa go out into blood via facilitated transporters, enter portal vein on way to liver
43
Tryptophan deficiency
Hartnup disease
- loss of tryp bc of defective transporter
- 4Ds, less severe than pellagra
- affects brain and skin
44
Niacin
(Vit B3)
- made via tryptophan
- deficiency: pellagra (4Ds)
- precursor to NAD and NADP
45
Lysosomal proteases to degrade proteins
Cathepsins: effective at degrading extracellular proteins
46
Ubiquitin/Proteasome pathway (UPP)
Major path of degrading intracellular proteins
Ubiquitin signals
1. N-end rule (methionine at end)
2. Pest sequences (proline, glutamate, serine, threonine) * in protein sequence
3. destruction boxes
4. phosphorylation
5. denaturation/damage
6. facilitators/chaperones (HPV E6 recruits E6-AP)
47
HPV E6 and p53
HPV E6 recruits E6-AP (an E3 ubiquitin ligase) which recognizes and ubiquitinates p53 --> driven to proteasome --> reduced p53 --More rapid cell cycle, increased # cells
48
Parkinson's
```
Parkin mutation (parkin=E3 ubiquitin ligase)
or
UCHI mutation (UHCI=deubiquitinase)
```
tx: L-dopa
49
Kwashiorkor disease
insufficient protein/inadequate protein (total calories are OK), start to lose nonessential proteins in body, lose albumin, flaky skin
50
+ N balance
pregnancy, muscle building, growth
urea excreted will decrease or not change
Growth due to deposition of protein
51
- N balance
insufficient protein/incomplete dietary protein, trauma
loss of protein due to use of body protein
urea excreted will increase
52
4 forms of N excretion in urine
ammonia, urea, creatine, uric acid
53
alpha-ketobutyrate
formed by degradation of methionine --> homocysteine --> cystathione --> alpha-ketobutyrate
also formed by de??
54
Synthesis of methionine
Homocysteine + methyl form THF --> methionine (via methionine synthase)
55
If methionine is deficient, what else is also deficient?
Cysteine (methionine --> homocysteine (via SAM))
56
Which syntheses require tetrahydrobiopterin?
Phenylalanine --> tyrosine (via phenylalanine hydroxylase)
| Tyrosine --> dopa (tyrosine hydroxylase)
57
Describe the folate trap
Methylene form THF --> methyl form THF is IRREVERSIBLE
only other way to get back to THF is through homocysteine + methyl form THF (via methionine synthase and B12) --> methionine + THF
So if B12 deficiency, also secondary deficiency in folate
58
aa only made through 1C transfers
glycine
serine
cysteine
methionine
59
Rxns req folate
1C transfers between serine and glycine
(serine + THF --> glycine + methylene form THF)
Synthesis of methionine
(homocysteine + methyl form THF --> methionine + THF) via methionine synthase
De novo purine synthesis
60
Path to phosphocreatine (ATP reservoir in muscle)
arginine --> glycine --SAM--> creatine --> phosphocreatine
can react with ADP to form ATP
OR
can convert to --> creatinine (*indicator of renal function)
61
Homocystinuria
Due to cystathione synthase defect
increased homocystine in urine
tx: supposed B6 (PLP), choline/betaine, folate, restrict methionine (low protein diet)
62
_________ conjugation with serine generates cystathione
homocysteine
63
CPSII
(1st step, pyrimidine biosynthesis)
glutamine + HCO3- + 2 ATP --> carbamoyl phosphate
Stim via PRPP and ATP
Inhib via UTP, UMP *allosteric inhib
64
Origins of pyrimidine ring
glutamine amide, aspartate, HCO3-
65
Origins of purine ring
glutamine, glycine, THF, aspartate
66
Enzymes of pyrimidine synthesis
```
CPSII*
aspartate transcarbamoylase
dihydroorotase
dihydroorotate dehydrogenase
orotate phosphoribosyl transferase
orotate phosphoribosyl decarboxylase**
UMPK
nucleoside diphosphate kinase
CMP synthase
```
67
orotate phosphoribosyl transferase
orotate phosphoribosyl decarboxylase
Regulation and deficiency
Inhibition via UMP
Absence --> orotic aciduria (orotic acid excreted, severe anemia, failure of normal growth
68
Salvage pathway of pyrimidine synthesis
Base --> NS --> NT
Pyrimidine --phosphorylase--> pry-ribose --kinase--> pyr-ribose-phosphate
69
Pyrimidine catabolism enzymes
NT--> NS --> base
*yields soluble prods
phosphatase
cytosine deaminase (cytidine-->uridine)
pyrimidine NS phosphorylase
70
Deoxyribonucleotide synthesis
Via ribonucleotide reductase (removing 2'OH of ribose of nucleotide diphosphates)
G/A/U/C-DP --> dG/A/U/C-DP
Uses NADPH
71
Buildup of dATP
SCID (bc dATP buildup inhibits ribonucleotide reductase)
72
Thymidine synthesis
dUMP --> dTMP (via thiamine synthase)
req. Methylene THF
73
fDUMP
Covalent binding of FdUMP to thymidylate synthatase inactivates the enzyme. (F --> very electroneg)
Useful for chemo
74
Methotrexate
Folate analogue
Competitive inhibitor of dihydrofolate reductase
--> cant regenerate THF --> prevents tumor growth
75
Hydroxyurea
Inhibitor of tyrosine radical of ribonucleotide reductase (inhibits tyrosine radical)
76
Insulin vs. glucagon (glycolysis regulation)
Insulin --> PFK2 activated --> more F26BP --> stim PFK1 --> glycolysis
Glucagon -->cAMP --> PKA --> inhib PFK2 --> less F26BP-> inhib PFK1 --> inhib glycolysis, promote gluconeogenesis
77
Insulin vs. glucagon (hormone-sensitive lipase regulation)
Insulin decreases HSL (increases lipid deposition)
Glucagon increases HSL (increases mobilization of FA to circulation to be used by muscle, etc)
78
aa used to make creatine
methionine, arginine, glycine
79
Increased homocysteine --> increased arterial disease
Admin with what will reduce homocysteine levels?
Folate
80
Purine catabolism enzymes
NT--> NS --> base + R-1-P
phosphatase
adenosine deaminase
purine nucleotide phosphorylase
81
polyamines
exp. spermine, binds DNA
82
Most of the ammonia used by CPSI comes from...
from glutamate or glutamine through the action of glutamate dehydrogenase and glutaminase, which are both present in liver mitochondria
83
The two atoms of N of urea enter the cycle at two points...
One as carbamoyl phosphate synthesized from free ammonia, the other as the amino group of aspartate:
84
NAG is synthesized from ...
| ^ synthesis is stimulated by...
acetyl CoA and glutamate
stimulated by arginine
85
serine dehydratase
serine --> pyruvate
| releases free ammonia
86
What directly provides carbon skeleton in cysteine synthesis?
SERINE
