Exam 1 Flashcards
different ways phospholipids can be made
2 FA to glycerol 3 phosphate makes phosphatidic acid
diacylglycerol reacts with an alcohol
either diacylglycerol or alcohol is activated first
sphingolipids special?
sphingosine backbone instead of glycerol
key component of myelin sheath
lipid diversity
big diversity within and btwn species
immune system can target bacterial glycolipids
lipases
hydorlize ester bonds within lipids
Pancreatic turn diety triglycerols into FA and monacylglycerol to get absorped
hormone sensitive lipase in adipose to break down to free fatty acids to share
lipoportein breaks down triglycerols os they can enter cells
phopholipases
hydrolyze phospholipids
to release energy or for cell signalling
can release arachidoinc acids
eiconosoids
local hormones from arachidonic aiid
can cause inflamation and platetlet aggregation among other things
arachidonic acid
released from phospholipids by phopholipases
PGHS
catalyzes RLS in two step prostanoid biosynthiesis (arachidoninc acid to protaglandin) and target for NSAIDs to inhibit as antiinflammatory
5-lipoxygenase
catalyesses committed step in leukotriene biosynthesis
related to asthma
effects of protaiglandins
prostacyclin-vasodilation and reduce platele aggregation thromboxane - vasoconstriction, increased platelet aggregation, bronchospasms
effect of leukotrienes
mediate symptoms of asthma
why do lipids require dedicated solubilization and transport mechanism
not water soluble on their own
solubalized by bile salts (detergents) in digestive tract
apolipoproteins form complexes to make solubalized ones travel
three lipoprotein pathways for lipid transport
chilomicrons - make exogenous lipids available trhought body, triacylglycerol +apolipoproteins
VLDL - triglyercols in ER of liver cells combined in ER lumen with apolipoproteinsthen sent out as VLDL particls
HDL - cholesterol transport
VLDL and HDL are endogenous
all three are broken up by lipoprotein lipase to enter target cells
COX1 vs COX2
COX1 - constitutively housekeeping
COX2 - regulated and pro inflammatory (makes prostanoids)
cis unsaturated fatty acid vs tans unsaturated fatty aid
cis is more common and causes kink
trans dont pack well and make membrane too rigid
regulatory mechanism that prevents beta oxidation of fatty acids while you are trying to synthesis palmitate
i think malonyl coA upregualtes faty acid synthesisi but down regulates beta oxidationpal
why need shuttle to transpoert acetyl COA in mito to cyto
CoA cannot crosss the innermito membrane
so turn acetate into citrate and then back
relationship btwn beta oxidation and gluconeogeneisis
beta oxidation makes NADH and ATP used in gluconeogensis
epinephrines effect on adipocytes
d
how are KB an important fuel source
can be used by brain during a starving state
can be made in but not used by the liver
Differentiate between saturated and unsaturated fatty acids.
saturated means no doublle bonds
Describe how the acetyl-CoA is delivered to the cytosol.
turn acetyl coa into citrate with citrate synthase, move it accrose then citrate lyase makes acetyl coa in cytosol
Discuss the steps and regulatory mechanisms of acetyl CoA carboxylase
acetyl CoA +CO2 +ATP to malonyl CoA
committed and ratelimint of FA biosynthesis
irreversible
allosteric: citrate up malonyl CoA down
covalent regulation: deph up phosh down
Biotin (vit B7) prosthetic group needed
Describe the fatty acid synthase enzyme
1 protein w/ 6 active sites
4 repeating steps: condesnation reduction dehydration reduction to keep adding 2 C from acetyl coa a
starts with 2 C from malonyl coA
thiolyase cuts it off at palmitic acid with 16 C
long term transcriptional control and only active as dimer
• List the repetitive steps in fatty acid synthesis
condense
reduce
dehydrate
reduce
• Describe the activation of free fatty acids in hepatocytes
d
• Describe the activation of free fatty acids in hepatocytes
activation with CoA ester
• Discuss the purpose and regulatory steps of the carnitine shuttle
CoA derivatives cant cross the inner mitochondrial membrane
so Fatty Acyl Coa gets through outter membrane then CPT I trades CoA for carnitine so fatty acylcarnitine can use a translocase to get to matrixe where CoA is swapped back for carnitine
CPT 1 is rate limiting and regulated by malonyl CoA which inhibits it
• Explain the role of FAD and NAD+ in β-oxidation.
FAD for first dehydrogenation
NAD for second dehydrogenation
• List the repetitive steps in β-oxidation
dehydrogenation, hydration
dehydrogenation
thiolysiis
• Understand the link between β-oxidation and gluconeogenesis
beta oxidation makes NADh and atp for gluconeogenesis
• Describe the steps of ketogenesis.
in mitochondria of liver with a lyase
• Discuss how cells can use ketone bodies as metabolic fuel
gives Acetyl CoA to the TCA for ATP
d• Compare and contrast the initial steps of cholesterol biosynthesis and ketogenesis.
both have 2 acety CoAs condensed to form acetoacetyl CoA and then a thrind added to form HMG-CoA
initial steps of cholesterol biosyn vs ketogenesis
both have 2 acetyl coAs condensed to form acetoacetyl CoA which have a 3rd acetyl coa added to form HMG - coa
• Explain and discuss in detail the regulation and importance of HMG CoA reductase.
RLS of HMG COa to mevalonate by HMG coa reductaase
major control point for entire cholesterol biosyn pathway
statins synthetic and natural can inhibit this
regulation and importance of HMG coA reductasse
RLS is HMG coA to mevalonate by HMG CoA reducase
• Compare and contrast the roles of chylomicrons and VLDL particles.
Chylomicrons are for dietary lipids
VLDL are fore endogenous ilipids
both delevir lipids to muscle and adipoose
CHylomicron remnats bring cholesterol to liver
VLDL become LDL when they are mostly cholesterol
Describe the role of LDL particles and be able to explain how cholesterol is delivered
and stored in cells.
brings cholesterol to cells not really sure
supply cholesterol to tissue by binding to receptors which can be blocked by drugs
• Discuss HDL-mediated reverse cholesterol transport (cholesterol efflux).
brings cholesterol out of the body smallest and densest takes to liver mostly takes liipids from VLDL but those get degraded idk how much detail
If a patient were taking statins to reduce their cholesterol levels, what other side effects
might you anticipate? (consider the importance of the isoprenoid pathway)
loss of dolichol or anything else downstream like ubiquinone could happen
What will happen to the levels of HMG CoA Reductase in the presence of high
intracellular concentrations of sterols? Why?
high sterols mean high insigs mean ubiquitin ligating enzymes and degredation of HMG CoA
What is the role of ‘insig’ in the regulation of HMG CoA Reductase?
it associates to a ubiquitin so it degreades HMG CoA
f a patient had a mutation in apoC-II that led to a dysfunctional protein, what should
build-up in the blood? Will it matter if the patient has been fasting or as just eaten a big
meal?
Lipoprotein lipase is activated by presensce of apoC-II so without it Chylomicrons and VLDL would both build up in the blood,
I dont think it would matter as far as relative amounts in regardss to the fed/fasting state cuz it should be higher than normal in either
- What is the difference in the roles of chylomicrons and VLDL particles?
Chylomicrons are for exogenous
- Why is LDL considered to be bad cholesterol, while HDL is considered to be good?
LDL delivers cholesterol while HDL removes it from tissue
• Describe the relationship between cholesterol and the steroid hormones
cholesterol is the building block of all steroid hormones and it converted to the pregnenalone precursor by Cytochrome P450
• Outline the function and general features of the cytochrome P450 enzymes
inserts oxygen into substrate and reduces other oxygen to water
step 1 lipid substrate and CYP ferric ion tae e from NADH
step 2 give e to O2
step 3 oxidize substrate
gets cholesterol into inner membrane
makes pregenalone by cleaving side chain of cholesterol
Define the pathway leading to the synthesis of steroid hormones in the adrenal
cortex
pregnenolone to progesterone before aldosterone or cortisol
regulated by hormone receptor interactions
Discuss the synthesis of pregnenolone and its relationship with the other steroid
hormones
is is the fist step after cholesterol and is the prohoromone precursor of all other hormones
cleavage of side chain of cholesterol by cytochrome p450 does this
Describe the general function of aldosterone, glucocorticoids, androgens and
estrogens
aldosterone - raoses BP and FL and Na uptake
glucocorticoids - like cortisol effects stress, BP and immune system
androgens - like testosterone for male sex characterisitics
estrogen - estradiol female sex characterisitics
Define how steroid hormones activate their receptors and exert their biological
response
hydrophobic so slip through membrane
bind to receptor causeing dissascoiation of HSP and exposing NLS of TF which goes to effect DNA
Define nuclear receptors
transcription factors that get activated by steoirids
• Compare general transcription factors with specific transcription factors
general - throughout all Transcription
specific regulate levels
nuclear receptors do this,
• Contrast transcriptional activation with transcriptional repression
activation by methylation to open up chromatin and repression to close chromatin
• Define the general structure of nuclear receptors
trans activation domain
DNA binding domain
hinge domain
ligand binding domain
• Describe the metabolic effects and immune effects of cortisol
fight or flight so gluconeogenesis up, aa catabolism up, glucose to muscles, fat breakdown up
reduces inflammation
Compare the general differences between type 1 and type 2 nuclear receptors
and provide examples of each
1 steroid glucocorticoid receptor 2 non steroidal for growht and develeopment PPARs heterodimers
essential aa
from diet
Phe, Val, Thr, Trp, Ile, Met, His, Leu, and Lys
ketogenic
only degrade to ketone bodies
leucine and lysine
keto-glucogenic
phenylalanine
isoleucine
tryptophan
tyrosine
transamination
transfer of alpha amimno group from aa to alpha keto glutartate makinge alpha keto aid and glutamate no net loss of nitrogen reversible catalyzed by ubiquitous enzymes aminotransferases highly specific coenzyme req: pyridoxal phosphat PLP 2 steps alpha-NH2 transfer second alpha NH2 transfer
oxidative deamination
removes amino gropu from glutamate making ammonia and alpha KG
uses NAD and NADP
ammonia transport and detoxification
found in blood in Gln and Aln
Glu + ammonia to Gln
liver takes ammonia from Gln and Aln for urea cycle
Urea cycle
ammonia to non toxic urea to platelets to kidneys and out
uses 4 ATP
5 rxns 2 mito 3 cyto
RL enzyme of urea
CPSI enzyme involved in formation of carbamoyl phosphate
requires allosteric activator NAG
UC regulation by substarte concentratin, NAG activator
changes in enzyme concentration
UC diseases
x-linked OTC deficiencty leads to hyperammonemia
restric diet and add aa analogs without ammonia
n scavenging drugs
antibiotics reduce gut bacteria
try to prevent hyper, and promote development
BCAAs and primary site of metabolisim
leucine, valine, isoleucine.
skeletal muscle
2 aa from BCAA
ala from transamination of pyruvate
gln
glucose alanine intertissue cycle
transfer between muscle and liver
ala goes to liver glutamate and pryvate reform
Glu is deaminated, NH3 enters UC
pyruvate is used for gluconeogenesis and sent to muscle
pyruvate from muscle or BCAA to ala to liver to pyruvate to glucose to blood to muscle
coenzyme from tryptophan
and diseases
NAD and NADP
deficiency causes pellagra
4 Ds
tyroseine
nonessential but made from essential Phe with PAH enzyme and coenzyme TBH/BH4
deficiency pf PAH makes PKU - minor pathways become major causing buildup and mousey odor
treatment is low Phe and tyr supplement
alkaptonuria
deficiency in homogentisate oxidase
first inborn error disease identified
dark pigment one from oxidation
cant degrade tyrosene
low homocystein levels? 2 pathways
high leves are associated with vascular disease
1 hcy remeth to met requires vit b12
2) Hcy + ser = cystathionine
folate trap
deficient vit b12 makes THF trapped in one useable form so hcyy levels increase
SAM
s-adenosylmethionine
Met condesnes with ATP to form this
cone carbon carrier of methyl group
cosubstrate
THF
cosubstrate
one carbon carrier for methylene, methenyl, formyl
also methyl for hcy tomet
biotin
prosthetic group
one carbon carrier for CO2
a couple biotin dependent carboxylations
PLP
coenzyme for aminotransferases
derivative of Vit B6
covalently linked to lysine
THB(BH4)
coenzyme synthesized from GTP
used in hydrozylation
Generation of SAM
met condesnse w/ ATP
hydrolysis of all three P gropus
activating methyl group
2 aa from BCAA
d
first three steps of BCAA catabolims, enzymes, reducing equivalents producets, and specifice metabolic ends of each BCAA
transamination - BCAA aminotransferase: glu and some alpha stuff
oxidative decarboxylation - BC alpha keto acid dehydrogenase: CO2, NADH, iso iso alpha methyl
dehydrogenation: FADH2, acetoacetate and acety co a, propoinyl coa and succinyl coa
pathology from BC alpha ketoacid dehydrogenase deficiency and treatment
maple syrup urine disease because of accumulation of BCA and keto acids
dietary modification and BCAA free formula and essential aa supplements
tyroseine
d
alkaptonuria
d
low homocystein levels?
d
liver
maintains fasting blood glucose G-6-ptase ketogenesis selflessly uses fa and aa UC FA oxidation and TAGs in VLDL
SAM
d
THF
d
biotin
d
PLP
d
THB(BH4)
D
Generation of SAM
d
glucogenic
other 14 aa become pyruvate or a TCA intermediate
first three steps of BCAA catabolims, enzymes, reducing equivalents producets, and specifice metabolic ends of each BCAA
d
glycogen
short term reserve liver and kidney systemic muscle local (no phosphotase)
fat
long term energy reserve (amount=time)
in adipose as TAG
glycerol no fa for gluconeogenesis
protein
long term
stored as muscle as last resort
glucogenic aa for glucose
liver
maintains fasting blood glucose G-6-ptase ketogenesis selflessly uses fa and aa UC FA oxidation and TAGs in VLDL
muscle
local store only
pyruvate to lactate sent to blood then used in liver for gluconeogenesis
transaminase BCAA
insulin depended glucose uptake
adipose
stores FA as TAG from VLDL
sends fa to liver and muscle
sends glycerol to liver and kindey
brain
requires glucose
can use ketone bodies when starving
never fatty acids
enzymes of storage vs retreival
storage are dephosphoryalted to activate
