FOMweek2a Flashcards
1
Q
what is the main storage form of FAs in the body?
A
Triacylglycerols (TAGS)
2
Q
how is isocitrate dehydrogenase regulated?
A
isocitrate dehydrogenase
**inhibitted by high NADH/NAD+ (high energy conditions)
3
Q
2 functions of pyruvate/malate cycle?
A
1) transport acetyl CoA from mito to cytosol
2) malic enzyme generates NADPH to power FAS
4
Q
What is the key regulatory step in FAS? And what is its cofactor?
A
acetyl CoA —> malonyl CoA
catalyzed by Acetyl CoA carboxylase
***biotin is cofactor
5
Q
How is acetyl CoA carboxylase regulated (feed forward)?
A
Citrate allosterically activates
insulin increases transcription
Xylulose 5-p “ “
Insulin stimulates dephosphorylation, activating ACC
6
Q
How is acetyl CoA carboxylase regulated (product)?
A
palmitoyl CoA allosterically inhibits
phosphorylation by AMP-PK inhibits
glucagon–>cAMP–>PKA–>inhibitory phosphorylation
7
Q
HOw does malonyl CoA affect FAS
A
inhibits carnitine polmitoyl transferase I (CPTI) by preventing b-oxidation of new FAs
8
Q
FAS
A
makes FA
*happens in cytosol & 1 enzyme carries out all steps
9
Q
General steps in FAS
A
bond formation
reduction
dehydration
reduction
10
Q
Describe the structure of enzyme fatty acid synthase
A
large enzyme w/ multiple activities
- *phophopantetheinyl group linked to serine residue
- *cysteine sidechain = other subunit
11
Q
Bond formation in FAS
A
- 2 C’s (acetyl CoA & has w C) added to p-Sulfur
- then added to growing acyl chain on c-Sulfur
- subsequent 2 C units come from malonyl CoA
- **? C group from c-Sulfur transferred onto p-Sulfur chain
12
Q
1st reduction in FAS
A
keto group reduced to an alcohol
*NADPH+ & H+ powers the rxn
13
Q
Dehydration in FAS
A
removes water and introduces a C=C double bond
14
Q
2nd reduction in 1 cycle of FAS
A
C=C double bond is reduced
**also powered by NADPH+ & H+
15
Q
Dehydration in FAS
A
removes water and introduces a C=C double bond
16
Q
2nd reduction in 1 cycle of FAS
A
C=C double bond is reduced
**also powered by NADPH+ & H+
17
Q
unsaturation constrictions
A
*body can unsaturate C-C bonds if they are at least 9 C’s away from w end
18
Q
2 most important dietary unsaturated FAs?
A
linoleic (18:29, 2)
linolenic (18:39, 12,15)
19
Q
At what point does FAS stop adding 2 C units?
A
once FA chain has reached 16 C = palmitate
20
Q
how can arachidonic acid be made?
A
- cannot be made de novo
* can convert linolenic acid from diet innto arachadonic acid by introducing a C=C, elongating, then adding another C=C
21
Q
unsaturation process
A
Process:
- uses Fatty acyl CoA desaturase
- energy ultimately comes from NADH+ & H+
- Oxygen is the e- acceptor
- makes 2 H2o as by products
22
Q
How do FAs get into cells?
A
- VLDLs circulate & react with lipoprotein lipase (LPL)
- LPL cleases of FA so can enter cells
- get B-oxidized for energy in muscle & stored as TAGs in adipocytes
23
Q
TAGs are made up of what components?
A
3 FAs linked to a glycerol backbone (glycerol 3-p from glycolysis)
24
Q
cardiolipin
A
- component of inner mito membrane
- formed from phosphatidyl glycerol and CDP diacylglycerol
- inner mito membrane is rich in cardiolipin
25
What happens during TAG packaging?
TAGs are packaged in Golgi w/ apoprotein B-100 -->VLDL
| *form secretory vesicles that fuse to plasma membrane & release VLDL's into blood
26
How do FAs get into cells?
* VLDLs circulate & react with lipoprotein lipase (LPL)
* LPL cleases of FA so can enter cells
* get B-oxidized for energy in muscle & stored as TAGs in adipocytes
27
most important sphingolipid
sphingophospholipid sphingomyelin!
| in myelin sheaths of nerve fibers w/ choline head group
28
ether glycerolipids
aka plasmalogens
* have ether linkage on 1 C of glycerol backbone
* 1 FA tail
* 1 head group
29
sphingolipids
use ceramide instead of glycerol for their backbones
| *ceramide is derived from serine & palmitoyl CoA
30
most important sphingolipid
sphingophospholipid sphingomyelin!
| in myelin sheaths of nerve fibers w/ choline head group
31
gangliosides
serine backbone
oligosaccharides
NANA
32
cerebrosides
serine backbone
| ceramide AND either glucose or galactose attached at hydroxy-methyl group
33
globosides
cerebroside but w/ 2 or more sugars
34
Adiponectin
complementary to leptin
| *adiponectin receptors signal thru AMP-PK & PPAR, leading to suppression of FAS & increases FA oxidation
35
what does ratio of sphingomyelin to dipalmit...... in amniotic fluid tell us
indicates gestational term
* as ratio of phosphatidylcholine to sphingomyelin gets larger = the later in the pregnancy it is
* in few weeks before birth, ratio may decrease some
36
how does adipose function as endocrine tissue?
release peptide hormones leptin & adiponectin
37
Leptin
satiety hormone
* TAGs are hi, leptin secretion increases
* leptin acts thru JAK/STAT receptors in hypothalmus to depress appetite
38
cerebrosides
serine backbone
| ceramide AND either glucose or galactose attached at hydroxy-methyl group
39
globosides
cerebroside but w/ 2 or more sugars
40
lung surfactant
* prevent aveolar collapse
* most abundant: dipalmitoylphosphatidylcholine
* sphingomyelin is another example
41
what does ratio of sphingomyelin to dipalmit...... in amniotic fluid tell us
indicates gestational term
* as ratio of phosphatidylcholine to sphingomyelin gets larger = the later in the pregnancy it is
* in few weeks before birth, ratio may decrease some
42
how does adipose function as endocrine tissue?
release peptide hormones leptin & adiponectin
43
Leptin
satiety hormone
* TAGs are hi, leptin secretion increases
* leptin acts thru JAK/STAT receptors in hypothalmus to depress appetite
44
importance of gangliosides, cerebrosides, & globosides
severe mental retardation is often caused by inability to break down these molecules
*lysosomal storage diseases
45
+ Nitrogen balance
eating more protein then can be excreted
46
- N balance
eating enough protein that all of it can be secreted
47
Nitrogen balance
excrete as much N as consumed
48
examples of (-) N balance diseases
chachexia, anorexia, kwashiorkor
49
Nitrogen balance equation
N balance= N intake-urinary urea N- X
50
what is ammonia metabolism
fuel generation from AA
* derived C --> CO2 & H2o & energy
* derived N --> Urea & other N products --> urine
51
Which ion can cross membranes; NH4+ or NH3
NH3
| *in a ammonia solution w/ pH 9.3 the ratio of NH4+ = NH3
52
AA transport into gut lumen/turnover
* use secondary active transport gets AA & Na+ into cell
* facilitated diffusion gets AA to other tissues
* Na/K+ pump maintains balance w/in cell (expends lots of energy)
53
Glutamate role & conjugate ketoacid?
* a-ketoglutarate
| * amino group pool of the cell, for body to use
54
Aspartate rle & conjugate?
* oxaloacetate
| * donates both free and fixed N to the urea cycle
55
Alanine role & conjugate?
* pyruvate
* in fasted condition when muscle is working =break down of protein, so alanine is releasedin circulation where C-skeleton is used to replacedietary glucose (key role in gluconeogenesis)
56
glutamine role & conjugate?
* glutamate
| * transports N to liver for urea cycle
57
Fed State protein digestion & AA turnover
* dietary protein is broken down into AA in the gut
* insulin promotes storage of protein
* AAs enter blood, enter muscle cells, & cycle thru AA & protein pools
* **FAs from VLDL & carbs are main fuel sources
58
Fasted state protein digestion & AA turnover
* glucagon, cortisol, epinephrine & norepinephrine promote mobilization of stored proteins
* protein from muscles is broken down into AAs in muscles
* N is donated to glutamine (kidney or gut) or alanine (liver) to be carried outside muscle cell
* FAs from adipose (freed thru lipolysis) & carbs (gluconeogenesis) are fuel sources
59
glutamate dehydrogenase properties
* makes a-ketoglutarate from glutamate
* can fix free ammonium!
* reversible process
* can use NAD+/NADH or NADP+/NAdPH as e- acceptor/donor
60
function of the urea cycle
convert N to urea-->urine excretion
61
regulation of the urea cycle is done by what?
arginine, amount of N coming into cycle**, & transcriptional regulation
**big part of regulation
62
how does arginine regulate urea cycle?
High arginine:
1) increases NAG synthesis, which allosterically activates CPS-I
2) increases arginase activity
63
Defects in Urea cycle Sx's & common manifestations
*usually seen as hyperammonaemia or hyperglutinaemia
*neurons r targeted because glutamate depletion prevents synthesis of NTs
Sx: FTT, seizures, Ataxia, tremors, irritible, not eating
64
6 enzymes, 6 inherited disorders of the urea cycle, what is common among them all?
elevated blood [NH4+]
65
characteristic of urea cycle disorders downstream from CPS-I?
elevated urinary orotic acid
66
HHH syndrome
*ornithine/citrulline antiporter is defective
67
Ways to diagnose inherited disorders of urea cycle?
* measure free ammonium & BUN (blood urea N)
* AA panel
* test for orotic acid in urine
* plasma citrulline test
68
Tx for inherited disorders of urea cycle?
* low protein diet (often 1st step even when unsure of which enzyme is malfunctioning)
* N-carbamoylglutamic acid
* eliminate N in other pathways using: benzoic acid, phenylbutyrate, arginine
* liver transplant/hepatocyte transusion
69
3 key cofactors in AA metabolism
* PLP: transaminations, deaminations, C chain transfers
* FH4: 1 C transfers
* BH4: ring hydroxylations
69
3 key cofactors in AA metabolism
* PLP: transaminations, deaminations, C chain transfers
* FH4: 1 C transfers
* BH4: ring hydroxylations
70
nonessential vs. essential AA
non-essential: we can make from glucose & N of other AA; 11 of them
* essential; must get in diet; 9 of them
* **children need arginine in diet, adults dont
70
Essential AAs
```
M. V. Pitthall
M=methionine
V=valine
P=phenylalanine
I= isoleucine
T= tryptophan
T=threonine
H=histidine
A=arginine*
L=leucine
L=lysine
```
70
What AA is made from phenylalanine?
Tyrosine
| *if phenylalanine (or enzyme phenylalanine hydroxylase) is absent, tyrosine becomes essential
70
What is the pathway to get from 3-phosphoglycerate to serine to alanine?
3-phosphoglycerate-->serine-->2-phosphoglycerate -->pyruvate -->alanine
**or serine can make cysteine then pyruvate?
70
What AA uses sulfur from methionine to be synthesized?
cysteine
71
AA can be derived from and degraded into what 3 intermediate classes?
* Glycolysis intermediates
* TCA cycle intermediates
* Acetyl CoA & Acetoacetate (ketogenic AAs)
72
what AA is derived from pyruvate as glycolytic intermediate?
alanine
| *reversible process
73
where are ALT & AST normally expressed?
only in hepatocytes
| *in blood =liver damage
74
What is the pathway to get from 3-phosphoglycerate to serine to alanine?
3-phosphoglycerate-->serine-->2-phosphoglycerate -->pyruvate -->alanine
**or serine can make cysteine then pyruvate?
75
what is PAPS?
activated sulfur
* structure similar to ATP
* sulfate donor
76
What are the 2 ways glutamate is produced?
glutamate a-ketoglutarate
*enzyme = glutamate dehydrogenase
OR
a-ketoglutarate can be transaminated by aspartate aminotransferase (AST)
77
Name the 3 ammonium fixing enzymes?
1) glutamate dehydrogenase
2) glutamine synthetase
3) carbamoyl phosphate
78
WHat AA can be made from a-ketoglutarate in TCA cycle?
*glutamate-->proline, glutamate, &/or arginine
79
WHat AA can be made from oxaloacetate in TCA cycle?
*aspartate -->aspargine
80
what happens when a-ketoacid dehydrogenase is inactive? (deficient)
branched chain AAs can't be broken all the way down and are stuck in a-keto (conjugate) structure
*a-ketos build up & are secreted in urine
MAPLE SYRUP URINE DISEASE
81
describe the transition/reactions to get to/from glutamate to glutamine
glutamate-->glutamine
*uses ATP & NH4+ & glutamine synthetase
glutamine-->glutamate
*uses H2O & glutaminase
82
what is proline's special role in protein structure?
introduces inflexibility into proteins secondary structure
83
3 branched chain AAs are....
valine, isoleucine, & leucine
84
why can thiamin (TTP) be effective treatment for MSUD?
TTP is also decarboxylase so can make up for a-keto acid dehydrogenase
