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455 Cards in this Set

  • Front
  • Back
What two ways can you make Glycerol-3-P (glycerol backbone)?
1) rephosphorylate glycerol (only in the liver)
2) use DHAP from glycolysis (in all cells + liver)
Is glycerol-3-p in reduced or oxidized state?
reduced
Is DHAP in reduced or oxidized state?
oxidized
What catalyzes the reaction of DHAP to glycerol-3-p? (fatty acid synthesis)
Glycerol-3-phosphate dehydrogenase
What nucleotides are needed in the reaction of DHAP to glycerol-3-p? (fatty acid synthesis)
NADH
List the steps, in order of the extrahepatic pathway for triglyceride synthesis
glucose (put through glycolysis) --> DHAP --> Glycerol-3-P --> Triglyceride
What catalyzes the breakdown of triglycerides?
lipases
What are the three types of lipases?
pancreatic lipase

lipoprotein lipase

adipose (hormone sensitive) lipase
What's the role of pancreatic lipase?

Is it active in fed or fasted state?
How is it regulated?
breaks down DIETARY triglycerides to free fatty acids + monoacylglycerol (does not go all the way to glycerol)

fed state

regulated by amount of TG injested
What's the role of lipoprotein lipase?

What is it activated by?
Is it active in fed or fasted state?
breaks down lipoprotein triglycerides to free fatty acids + glycerol

activated by insulin
active in fed state
What's the role of adipose lipase?

What is it activated & inhibited by?
Is it active in fed or fasted state?
breaks down stored triglycerides to free fatty acids and glycerol

activated by glucagon+epinephrin & inhibited by insulin

active in fasted state
Do lipoproteins carry fatty acids or triglycerides to adipose tissue?
triglycerides
All glycerol from triglyceride lipolysis goes where?
to the liver
What special enzyme rephosphorylates glycerol to Glycerol-3-P?

Where is the one place this enzume is found?
glycerol kinase

in the liver
What is the fate of glycerol in fed and fasted states?
Fed - catabalyzed for energy via glycolysis; also could be rephosphorylated for synthesis of TG

Fasted - all glycerol in the liver is converted to glucose for gluconeogenesis
Abnormal Glyc-3-P dehydrogenase can lead to what clinically relevant pathology?
fatty liver. Commonly occurs in alcoholics. Can't turn glycerol to DHAP so the it remains in the liver. Also can't turn glycerol to glucose, so alcoholics can have decreased energy
Which glycolytic compound can be converted to Glyc-3-P?
DHAP
Would high NADH/NAD+ ration increase or decrease the Glyc-3-P DH rxn in making Glyc-3-P?
increase
As what compound does glycerol enter the glycolytic/gluconeogenesis pathways?
DHAP
Conversion of glycerol to DHAP is a reductive/oxidative process.

-pick one
oxidative
which hormone would logically activate lipoprotein lipase?
insulin
Is hormone sensitive lipase active or inactive when phosphorylated?
active
partially oxidized carbons, fatty acids, amino acids & ethanol enter the TCA cycle and are oxidized to what?
CO2
Where does glycolysis take place?
cytosol
Where does gluconeogenesis take place?
cytosol
Where in the cell does the reaction of pyruvate --> acetyl CoA get catalyzed?

what enzyme is involved?
in the mitochondria

pyruvate dehyd.
What does pyruvate carboxylase do?
converts pyruvate --> oxaloacetate in the mitochondria
What are the two carbon compounds pyruvate can be converted to that enter the TCA cycle?

Are either of these reversible?
Acetyl CoA (2 carbon) - makes ATP

Oxaloacetate (4 carbons) - uses ATP

No, neither is reversible back to pyruvate
When oxaloacetate (4 carbons) is made from pyruvate (3 carbons), where does the extra carbon come from?

What vitamin is needed as a cofactor to capture the extra carbon?
CO2

Biotin acts as a cofactor for this rxn
Where in the cell does TCA cycle take place?
in the mitochondria
What is the regulated enzyme in the TCA cycle?

what step it catalyze?
isocitrate dehydr.

isocitrate --> α-ketogluterate
what is the recycled component of the TCA cycle?
oxaloacetate
What happens to the CO2 made by the TCA cycle?
Gets converted to bicarbonate (HCO3-), bound to hemoglobin in the RBC, transported to lungs, gets converted back to CO2 and expelled by breathing
How many GTP's are produced by each TCA cycle?
one
What vitamin cofactors are required by the TCA? List 5 of them
TPP - Vitamin B1
FAD - Vitamin B2 - Riboflavin
NAD+ - Vitamin B3 - Niacin
Co-enzyme CoA - Vitamin B5 (pentothenic acid)
Lipoic acid (from lipoamide)
What is the role of Co-enzyme A (CoA-SH) in the TCA cycle?
has a lot of energy in its bond, which is used to transfer/activate acyl groups in the TCA cycle
What three enzymes utilize the NAD+ cofactor in the TCA cycle?

Are their intermediates reactive?
Isocitrate dehydr.
α-ketogluterate dehydr.
malate dehydr.

intermediates not reactive
With what method are electrons added to NAD+ to convert it to NADH?
2 electrons AT ONCE
What enzymes utilize the FAD cofactor in the TCA cycle?
succinyl dehydr.

succinate --> fumarate
What two cofactors are used by α-ketoglutarate and pyruvate dehydrogenase in the TCA cycle?
TPP
Lipoic acid
What carbon compound in the TCA cycle occurs before the RLS and can leave the TCA cycle and play a role in fatty acid synthesis?
Citrate

this product can leave the TCA, cross the mitochond. membrane and be converted to Acetyl CoA in the cytosol, which is needed for fatty acid synthesis

This is a FED STATE, HEPATIC process!!
How is the RLS in the TCA cycle regulated? (activate and inhibited)
isocitrate dehydr. (RLS) is activated by isocitrate, ADP and Ca (in skeletal mm)

inhibited by NADH & ATP
What happens when AA's enter the TCA cycle in the fed state?
1) AA further catabolized to CO2
2) converted to FA for storage as tryglycerides
What happens when AA's enter the TCA cycle in the fasted state?
used as carbon source in gluconeogenesis
In the TCA cycle, is transamination readily reversible?
Yes
What's the purpose of transamination in the TCA cycle?
Can make amino acids from TCA intermediates and vice versa
Below are the common products that undergo trasamination. List what each one becomes:

pyruvate (3C)
oxaloacetate (4C)
α-ketoglyterate (5C)
alanine (3C)
Aspartate (4C)
Glutamate (5C)
To be a gluconeogenic, an AA must feed into the TCA cycle at the ___________ step or later.

(list the intermediate of the TCA cycle)
α-ketogluterate
What's the fate of ketogenic AA if they enter the TCA cycle? (2 fates)
1) catabolized for energy
2) turned to ketons & used extrahepatically
Which TCA cycle carbon compound is a precursor to gluconeogenesis?

How is it transported?
oxaloacetate

oxaloacetate is converted to malate & aspartate and transported to the cytosol where it is made back to oxaloacetate
Does addition of acetyl CoA to the TCA produce new oxaloacetate?
No.

Start with a 4C oxaloacetate and end up with the same 4C oxaloacetate. Acetyl CoA's are expelled as CO2
What TCA intermediate is used in heme synthesis?
Succinyl CoA
What TCA intermediate is used in glutamate, glutamine and neurotransmitter synthesis?
α-ketogluterate
In the fed state, why would the liver produce a lot of citrate (intermediate of the TCA cycle)?
To start fatty acid synthesis, as a result of excess glucose or AA acid
What is the major problem in pyruvate carboxylase deficiency?
can't make oxaloacetate (from pyruvate)
What is the major source of acetyl CoA BODY WIDE in fed state?
pyruvate via pyruvate dehydr.
What is the major source of acetyl CoA BODY WIDE in fasted state?

how about in the brain & RBC?
-fatty acids via fatty acid breakdown (β-oxidation)

-pyruvate in the brain+RBC
Oxaloacetate can be made by transamination of _________?
aspartate
How is more oxaloacetate made?
by pyruvate carboxylase
In which part of the cell does β-oxidation occur?
In what state (fed/fasted)?
In type of cells in the body?
Occurs in the mitochondria

In the fasted state in all cell, except skeletal mm used it in fed or fasted state

In all cells except brain+RBC
Are naturally occurring double bonds in the cis or trans state?
cis
Fatty acids with roughly 6-12 carbons are considered what?
medium chain FA
Fatty acids with roughly 4 carbons are considered what?
short chain FA
Does β-oxidation by itself produce any ATP?

Is it an aerobic or anaerobic process?
No, only if its linked to TCA and Ox Phos

Aerobic only.
In fed state, where do the FA come from for skeletal mm β-oxidation?
when lipoprotein lipase breaks down chylomicrons or VLDL TG
In fasted state, where do the FA come from for skeletal mm β-oxidation?
FA from adipose tissue (regulated by adipose lipase)
In β-oxidation, what happens after long-chain FA crosses the cell plasma membrane?
get activated to fatty acyl-CoA by using ATP
After fatty acyl-CoA is formed (activated) in the cell, how does it get into the mitochondria?
Binds to CARNITINE; removes CoA, transports fatty-acyl into the mitochondria; CoA is re-binds to form fatty acyl-CoA (w/o the use of ATP)
What are the products of β-oxidation?
Acetyl CoA (1 acetyl CoA for 1 fatty acyl CoA)
NADH
FADH2
In β-oxidation, adipose lipase is only active in ________ state.

This lipase is regulated by 2 things..what are they?
fasted

regulated by glucagon and epinephrin
In β-oxidation, what happens to the β-carbon in order to produce NADH and FADH2?
becomes oxidized
Why does FAD form unstable intermediates?
Because FAD only accepts one electron at a time (total of 2), thus forming unstable radicals.
In β-oxidation of an odd # carbon chain, what are the main products?
one less Acetyl CoA & 1 propionyl CoA (3C) (instead of a second acetyl coA),

Odd chain means the odd carbon has to attach somewhere=propionyl
After propionyl Coa is made from odd-chain β-oxidation, what is its fate?
converted to succinyl CoA and can enter the TCA cycle at that step.
What are the products of unsaturated FA β-oxidation?
One less FADH2 is produced for EACH double bond

double bonds are more oxidized
What are the products of medium chain FA β-oxidation?
Cannot be broken down by all cells in the body, so travel DIRECTLY to the liver and get β-oxidized there.

- These are more water soluable, so not transported by lipoproteins

-Also NOT stored as adipose TG
What's the purpose of peroxisomal oxidation in β-oxidation?

Is it the same as regular β-ox?
Is the net result the same?
break down branch long-chain FA or very long fat (>20C)

Similar but not identicle to regular β-ox.

Yes, net result is same: make acetyl CoA that can go to TCA
What's the purpose of ω-fatty acid oxidation in β-oxidation?

What are it's products?
back up process of β-oxidation

produces dicarboxylic acids which are secreted into the blood and excreted into the urine (if increased = malf. β-ox)
Is β-oxidation MAINLY a fed or fasted state event?
fasted
Which cells NEVER use β-oxidation?
Brain + RBC
How are FA from adipose lipase transported in the blood stream?
bound to albumin
The glycerol product of adipose lipase action is used in the _________.
liver
What's another name for Complex I in Ox Phos?
NADH dehydr.
What's another name for Complex II in Ox Phos?
Succinate dehydr.
What's another name for Complex III in Ox Phos?
Cytochrome b-c complex
What's another name for Complex IV in Ox Phos?
Cytochrome oxidase
What's another name for Complex V in Ox Phos?
ATP synthase
What product receives electrons from NADH inside Complex I?

What's the other part inside this complex to which electrons get handed off?
FMN receives e- from NADH and hands them off to Fe-S
What does Complex I hand off its electrons to?
Coenzyme Q
Where does Coenzyme Q go to after it receives electrons?
takes them to Complex III
What does Complex III hand off its electrons to?
Cytochrome C
Where does cytochrome C take electrons to?
to complex IV
Electrons from FADH2 are initially transferred to what complex in Ox. Phos pathway?
Complex II
What subunits (and #) make up the ATP synthase complex?
3 β subunits - release ATP
3 α subunits
1 γ core - spins
What complex acts as an inhibitor/uncoupler of the Ox Phos pathway? (it produces heat)
thermogenin
What does brown fat have a lot of in it that produces heat?
mitochondria
What does the mnemonic RMACO stand for?
Real Mitochondria Always Consume Oxygen

Rotenone (Comp. I); Malonate (Comp. II); Antimycin A (Comp. III); Cyanide/CO (Comp. IV); Oligomycin (Comp V)
How many molecules of ATP do NADH and FADH2 yield?
NADH - 2.5 molecules of ATP

FADH2 - 1.5 molecules of ATP
Name the sources of free radicals within the mitochondria
coenzyme Q (largest source)
peroxisomes
NADPH oxidase
myeloperoxidase
ionizing radiation
Name the free radicals that can occur in the mitochondria
O2- (superoxide)
OH· (hydroxyl radical)
OONO· (ooooooo NO!)
NO· (nitric oxide)
Name the 3 enzymes used to eliminate free radicals
SOD - turns O2- to O2 and H2O2
Catalase - turns H2O2 to H2O and O2
Glutathione - used NADPH to reduce oxidizing agents
Name 3 reasons why mutations occur more frequently in mitochondrial DNA
- lack repair enzymes
- very active=makes a lot of ROS
-lacks histones=dna not protected
What is the problem in Leber's Hereditary Optic Neuropathy (LHON)?
mutation in complex I (NADH dehydr. deficiency)

No ragged red fibers
What is the problem in Maternal inhertied Leigh's sydrome (MILS)?
mutations in ATP synthase (complex V in Ox. Phos.) - reduced muscle tone
What is the problem in Myoclonus epilepsy with ragged red fibers (MERRF)?
ragged red fibers and Cytocrome C oxidase (COX) deficiency as a result of mutations in lysine tRNA gene
What is the problem in Parkinsons disease (PD)?
reduction of Complex I (NADH dehydr.) in the SNc (substantia nigra) of the brain that controls movement
Will pyruvate, FA & TG increase or decrease with mitochondrial diseases?
increase.
Mitochondria is needed for these things to be catabolyzed, so mitochond. diseases will cause a build up of these
Why does rotenone cause parkinsons disease?
rotenone irreversibly inhibits Complex I (NADH dehyd.), which is the main problem in parkinson's
What's the difference between chylomicrons and VLDL?

Do these occur in fed or fasted state?
Chylomicrons carry dietary TG
VLDL carries hepatic TG

Fed state
What is the largest source of gluconeogenic carbons?
skeletal mm
Can gluconeogenesis use fatty acid carbons to make glucose?
NO
Under normal conditions, net glycogen breakdown occurs in what tissues?
skeletal mm and hepatic tissues
Can skeletal mm export glucose?
no
In a short term fast, degradation of what provides glucose?
hepatic glycogen
In long-term fast, what provides blood glucose?
gluconeogenesis
Which enzyme faciliates storage of excess glucose as glycogen?
glucokinase
What enzyme allows formation and export of glucose in a fasted state?
gluc-6-phosphatase
What is the common intermediate between gluconeogenesis, glycolysis and glycogen?
Glucose-6-phosphate
What do resting skeletal mm catabolize?
fatty acids
what do contracting skeletal muscles catabolize?
glucose
What enzyme is skeletal muscle missing that's preventing it's transport of glucose?
Gluc-6-phosphatase
What are the starting materials for glycogen synthesis?

What enzymes are needed?
G1P (from G6P), UDP, glycogen core

glycogen synthase & branching enzyme
What are the products of glycogen degredation?

What enzymes are needed?
G1P and a bit of glucose

glycogen phosphatase & debranching enzyme
What 3 things regulate glycogen synth/degr?

What state are they active in (fed/fasted)?
Glucagon (fasted) + epinephrin

Insulin (fed) + epinephrin
Does glucagon phosph. or dephosph. things?

How about insulin?
glucagon phosphorylates enzymes

insulin dephosphorylates enzymes
What is the compound that does the actual act of phosphorylating enzymes when glucagon activates glycogen the pathway?
protein kinase A
In what situations is epinephrine needed for glycogen syn/degrd?
emergency situations such as hypoglycemia or skeletal mm contraction during fight-or-flight response
What product is found a lot in skeletal muscle that activates glycogen syn/degrd?
epinephrine
Abnormal glycogen processing or glycogen build up are symptoms of what disease?

What causes these problems?
glycogen storage disease

defective enzymes or G-6-P phosphatase
In myocardial ischemic conditions, where does net use of glycogen occur?
in the affected myocardial cells (remember, ischemia is localized; hypoxia is body wide)
Malate crosses from the hepatic mitochondria into the hepatic cytosol in __________ state. (fed/fasted)
fasted.

This is for gluconeogenesis, which is a fasted state process
What activates sugars?
UTP

Gluc-1-P + UTP == UDP-Glucose
UDP-Glucuronate + Bilirubin = what?
bilirubin diglucoronide
The addition of glucuronate adds what that makes hydrophobic molecules more water soluable?

Where does this occur?
How is this catalyzed?
a negative charge

in the liver
Catalyzed by glucuronyl transferase
Do you need to ingest galactose to make glucose?
No, galactose can be made from glucose since these two are epimers.
To make lactose, what starting materials do you need?
Glucose + UDP-Galactose
Which are important components of membranes, are antigenic and serve an important role in cell signaling and recognition?

Glycosaminoglycans, glycoproteins or glycolipids?
glycolipids AKA glycosphingolipids because they have a ceramide core
Which bonds link sugars(carbs) to asparagine?
N glycosidic bonds
Which bonds link sugars(carbs) to serine or threonine?
O glycosidic bonds
What's the disease called where there is a deficiency in lysozomal enzymes?
I-cell disease
Glucocerebrosides, galactocerebrosides and gangliosides share a common core molecule..what is it?
ceramide
What are glucocerebrosides made from?
reaction of ceramide + UDP-Glucose

There are ONE SUGAR compounds
What are galactocerebrosides made from?
reaction of ceramide + UDP-Galactose

There are ONE SUGAR compounds
What are gangliosides made from?
reaction of ceramide + two or more UDP-sugars & N-acetylneuraminic acid (NANA)

There are 2 OR MORE SUGAR compounds
Sphingolipidoses is a result of deficient degradation of ________
glycolipids/sphingolipids
Glycoproteinoses is a result of deficient degradation of _________
glycoproteins
Mucopolysaccharidosis is a result of deficient degradation of _________
proteoglycans/glycosaminoglycans/GAGs
What is the major source of glucose?
carbs
Name the enzymes responsible for phosphorylation of each:
Glucose
Fructose
Galactose
glucose - hexokinase or glucokinase on the liver
fructose - fructokinase
galactose - galactokinase
What places in the body metabolize fructose?
liver, intestinal mucosa, kidneys
(these places are where fructokinase is found in)
What places in the body metabolize glucose and galactose?
most tissues in the body
What reaction (name the substrates) does fructokinase do?
fuctose --> fructose-1-p
What reaction does aldose B do (specifically)?

Where is aldose B found in the body?
fructose-1-p --> glyceraldehyde in fructose pathway

found everywhere that fructokinase is found (need both enzymes to completely break down fructose)
What's the difference between Aldose A and Aldose B?
Aldose A - mainly in muscles and other cells

Aldose B - fructose pathway (liver, intestinal mucosa, kidneys)
Why is fructose more lipogenic than glucose?
because it bypasses the PFK1 regulation step (it enters glycolysis at the glyceraldehyde-3-p step, after PFK did it's thing)
What pathway synthesizes fructose from glucose?
polyol pathway
What are the three compounds of the polyol pathway? (starting, intermediate, product)
glucose --> sorbitol --> fructose
What's the purpose of aldose reductase in the polyol pathway?
turns glucose --> into sorbitol
Where in the body is the polyol pathway most used?
in the seminal vesicles, by spermatozoa
Under what conditions can sorbitol build up in cells?

What happens when it builts up?
hyperglycemic conditions = sorbitol builds up because there isn't enough of the enzyme to break down sorbitol to fructose. Sorbitol can't leave and builds up in cells

Build up causes cataracts
What molecule builds up with fructokinase deficiency and what are the symptoms?
excess fructose build up

causes no symptoms other than fructose in urine
What builds up in Aldose B deficiency and what are the symptoms?
fructose & Fructose-1-P build up

causes severe symptoms and fructose in urine
What builds up in galactokinase deficiency and what are the symptoms?
build up of galactose (& galacticol)

causes cataracts
What two molecules cause cataracts when they get backed up?

What's deficient in each case that's causing these to back up?
galactose (galactokinase) and sorbitol (not enough of the enzyme to convert sorbitol to fructose)
What builds up in GALT deficiency?

what are the symptoms?
galactose and galactose-1-p

cataracts AND liver damage
What builds up in a Glucose-6-P dehydr. deficiency?

what can't be made?
Glucose-6-P

G6P can't be made into Ribulose-5-P
What is ribulose-5-p used to make?
nucleotide synthesis
Which process in the PPP is reversible?

Is this also where NADPH is produced?
non-oxidative

NO
Which process in the PPP is irreversible?

Is this also where NADPH is produced?
oxidative

YES
What is the rate limiting step in the oxidative step of PPP?

How is it activated & inhibited?
G6P dehydrg

activated by insulin (after eating)
inhibited by NADPH
What factor is required by transketolase in PPP?

What reaction does this enzyme catalyze?
TPP (Thiamine, Vit. 1)

Glyceraldehyde-3-P (from glycolysis) to Rubulose-5-P (or vice versa)
Transketolase is used to diagnose __________ deficiency.
thiamine
Name 3 things that can cause G6P-dehydr. deficiency?
oxidative stress
drugs that are oxidizing agents (ANTIBIOTICS!!)
Fava beans..
G6P-dehydr. deficiency is an _______ disorder. (pick: x-linked, autosomal dominant, autosomal recessive, dank)
x-linked
Heinz bodies form from denatured ________
MetHB
What happens to carbons in the glycolysis pathway, oxidation or reduction?
oxidation of carbons
What is the majory regulatory step in glycolysis?
PFK1
What are the 3 types of enzymes used in glycolysis?
kinases - add a P from ATP
isomerases - relocate functional groups
Dehydrodgenases - catalyze diff. ox/red rxn's using nucleotides
What does hexokinase do in glycolysis?

Is it reversable?
cleaves glucose to G6P

No (but glucokinase rnx in the liver IS reversable, to make glucose from G6P)
What rxn is catalyzed by PFK1 in glycolysis?
F6P --> F-1,6-bisphosphate
What allosterically activates PFK?
F6P
Does ADP activate PFK?
No, because ADP gets converted to AMP and ATP by adenylate kinase

(2 ADP --> 1 AMP + 1 ATP)
What reduces NAD+ to NADH in the glycolysis pathway?
glyceraldehyde-3-P dehydr.

(this takes G3P and converts it to 1,3 bis-phosphoglycerate)
What 2 enzymes in glycolysis produce ATP?
phosphoglycerate kinase and pyruvate kinase
When acetyl coA is made from pyruvate, which one of these is a product: NAD+ or NADH?
NADH. Pyruvate becomes oxidized (think about the fact that it looses a C) and NAD+ becomes reduced to NADH
Product inhibitors of pyruvate dehydrogenase activate or inactiavate kinase?

What happens after this occurs?
kinase gets activated, which then goes on to phosphorylate pyruvate dehyd. and turn it OFF
Cori cycle is active in the fed/fasted state (pick one) during aerobic/anaerobic metabolism (pick one).
active during fasted state in anaerobic metabolism
What happens to the lactate made by skeletal mm?
gets sent to the liver for gluconeogenesis; glucose is made and returned back to the skeletal mm
When pyruvate gets converted to lactate, what is a product, NAD+ or NADH?
NAD+
Name the 2 shuttles that transport e- into the mitochondria.

Are these active in aerobic, anaerobic or either condition?
G3P & malate/aspartate shuttles

Active ONLY in aerobic conditions. (no point in putting e- into mitochondria if there isn't oxygen to run any of the pathways (mitochon. needs O2))
Why have 2 e- shuttle systems?
assures rapid NADH reoxidation
What intermediate in the glycolysis pathway can enter into the PPP?
G6P
What intermediate in the glycolysis pathway can be converted to a product used by RBC?
2,3 BPG is made from 1,3BPG (bisphosphoglycerate)
Say which of these processes are cytosolic and which ones occur in the mitochondria: glycolysis, B-oxidation, TCA cycle, gluconeogenesis, fatty acid synthesis, ox. phos.
cytosolic - glycolysis, gluconeogenesis, fatty acid synth.

mitochondria - B-oxidation, TCA cycle, ox. phos.
Why does pyruvate need to be converted to lactate under anaerobic conditions?
Pyruvate can't leave the cell, but lactate can. Otherwise pyruvate would build up and cause problems
In the fed state, what's the fate of lactate?
1) catabolized in aerobic cells (heart)

2) turned to fatty acid storage in the liver (when lactate is in excess of ATP)
In the fed state, all cells except ________________________ use glucose to make ATP.
non-contracting skeletal mm
Amino acids can be used for energy in fed/fasted state, or both?
BOTH
What part/s of a protein (amino acids) can be catabolized and what part cannot?
carbons are catabolized
nitrogen is converted to urea and excreted
Arachidonic acid is an omega __ FA..
omega 6
What's the structure of arachidonic acid?
20C with 4 DB
What does phospholipase A2 do?
cleaves phosphilipds to arachidonic acid
What is phospholipase A2 inhibited by?
steroid type drugs such as glucacorticoids
What are prostoglandins and thromboxanes cleaved by?
cyclooxygenases (COX)
What are leukotrienes cleaved by?
lipoxygenases
What are epoxides cleaved by?
cyctochrome P450
Which eicosanoids regulate pain, coagulation, fever and inflammation?
prostaglandins and TxA2
Which eicosonoid, when activated, opens channels that allow chloride transfer?
PGE2 (prostoglandin family E)
What prostoglandin reverses activity of TxA2
PGI2
What's the funciton of leukotrienes?
bronchoconstrictor
What enzymes does Aspirin and other NSAIDs inhibit?
With what method do they bind?
What's products are not made when Aspirin is taken?
COX1 and COX2

irreversibly at the active site

prostaglandins are not cleaved from arachidonic acid
What COX enzyme is constituative? What does this mean?
COX1

means it's always on
Which COX enzyme is inducible?
COX2
Which eicosonoid plays a role in appetite?
anandamide
Which eicosonoids, not formed from COX enxymes, play a role in inflammation?
isoprostane and anandamides
What is a clinical use of isoprostanes and anandamides?
Serve as biomarkers for oxidative damage

they eliminate free radicals and excreted in the urine..can be identified
Are isoprostanes and anadamide also prostoglandins?

Are they formed using the COX enzymes?
yes

no
What three things require cholesterol as their starting material?
Bile acid synthesis

Vitamin D synthesis

Steroid hormone synthesis
Can cholesterol rings be broken down once formed?
NO
Do cholesterol esters regulate the rate of cholesterol synthesis?
NO
At high levels of insulin, what happens to HMG CoA reductase?
dephosphorylated and activate
What form for cholesterol (esterified or deesterified) can be transfered between lipoproteins?
esterified cholesterol ONLY
Production of what is controlled in the bile acid synthesis pathway?

How is turned off?
7alpha-hydroxycholesterol

feedback inhibited by high bile salt levels
What are the primary unconjugated bile salts
cholic acid and chenocholic acid
What's the purpose of conjugating bile acids?
to make them more water soluble by making them hydrophilic
What are the primary conjugated bile acids?
taurocholic and glycocholic

taurochenocholic and glycochenocholic
How are secondary conjugated bile acids made?
by bacterial action on the 4 primary conj bile sales in the intestine
What are the secondary conjugated bile acids?
deoxycholic and lithocholic acids

deoxychenochilic and lithochenocholic acids
In a fasted lived, serum TG levels are proportional to serum _____ levels.
VLDL
What lipoproteins deliver things made in the liver to skeletal mm and adipose tissue?
VLDL
What lipoprotein delivers cholesterol to cells?
LDL
Which apoprotein can be a marker for CAD?

What is it made out of?
Lp (a)

LDL and apoprotein a
Which apoprotein binds lipoproteins to LDL receptors in the liver?
Apo E
Chylomicrons are made in the _________ and transport _________ TG and cholesterol to ________ and __________. (fill in the blanks)
made in the intestine

transport dietary TG and CH

to skeletal mm and adipose tissue
What does a nascent chylomicron contain?
TG and cholesterol
What does a mature chylomicron contain?
TG, cholesterol, Apo CII and Apo E
Chylomicron makes two stops to drop off it's contents. Where does it stop and what does it drop off?
Goes skeletal mm and adipose to unload TG

Goes to liver to unload dietary cholesterol
Where is VLDL made and when is it active?
made in the liver..active in fed state
What has to happen for VLDL to become IDL?
TG must be unloaded
What are the 2 routes IDL can take once it's formed?
Can become LDL

Returns to liver via hepatic LDL receptors to be degraded
What's the function of HTGL (hepatic trigyceride lipase)?
It helps to IDL become LDL by transferring the TG from IDL to HDL
What are the three sources of cholesterol on LDL?
VLDL (hepatically synthesized)

Diet

HDL (picked up from cells)
What happens if there is excess LDL in the serum?
Increases oxidation = increases free radicals = increase in atherosclerosis
What's the purpose of the SRB1 receptors?
The are nonspecific scavenger receptors that take up cholesterol delivered to the liver directly from HDL
What do statin drugs affect?
decrease HMG CoA reductase
What regulates calcium absorption and reabsorption?
Vitamin D
From what common system compound is cholesterol synthesized from?
Acetyl CoA
What is the rate liming step for all steroid pathways?
CPIIA1 (AKA Cyt P450)
What helps cholesterol enter into the mitochondria?

What receptors are used?
StAR protein

LDL and SRB1 (scavenger)
Progesterone is synthesized into what?

What intermediate is used?
Aldosterone and cortisol

17alpha-hydroxy-progesterone
Pregnenolone is syntheized into what?

What intermediate is used?
DHEA, which will be

17alpha-hydroxy-prognenolone
What enzymes are required for aldosterone synthesis?
CYP21, CYP11B1 and CYP11B2
What enzymes are needed for the production of cortisol?
CYP17, CYP11B1 and CYP21A
What enzymes are needed for the production of DHEA (precursor to androgens)?
CYP17
Stimulation of the hypothalamus stimulates what?

What hormones are used in the process?
Anterior pituitary

CHR & VP
What releases ACTH?
anterior pituitary gland
What's produced by the HPA axis?

What inhibits it?
cortisol is produced & also inhibits HPA
Does cortisol cause hyper or hypoglycemia?
hyperglycemia (by inhibiting glucose uptake...so glucose hangs out in the serum)
Does cortisol cause hyper or hypotension?
hypertension
Does cortisol cause hyper or hyponatremia?
hypernatremia (too much sodium in the blood)
What's causes Addison's disease?
cortisol deficiency
What does cortisol, ACTH and hyperpigmentation have in common?
decreased cortisol causes increase in ACTH (nothing to feedback inhibit it), which stimulates MCR2 (melanocyte enzyme) and causes hyperpigmentation
What's the next product formed from DHEA?
androstenedione
Androgen formation is regulated by what hormone?

Where is this hormone made?
Lutenizing hormone (LH)

anterior pituitary
What cells secrete primarily androgens?
theca and stromal cells
What cells secrete primarily estrogens?
granulosa cells
What cells secrete primarily progesterone?
corpus luteum
Cushing syndrome, adrenal carcinoma and congenital adrenal hyperplasia are all causes by a deficiency in what? Who's affected?
deficiency in adrenal androgens

affects females
Which enzyme causes estrogen formation?

What is it regulated by?
aromatase

regulated by follicle stimulating hormone (FSH)
What is the primary control method for aldosterone?

What are 2 others?
renin-angiotensin pathway

ACTH and dopamine
Does increase in aldosterone cause an increase or decrease in BP?
increase
Does increase in aldosterone cause hyper or hyponeutrimia?
hyperneutrimia (same as cortisol)
Does increase in aldosterone cause hyper or hypokalemia?
hypokalemia (low serum phosphate)
Does increase or decrease in aldosterone cause acidosis?
decrease in aldosterone (less plasma volume..more concentrated)
What is the cause of Primary Aldosteronism?
increased aldosterone

causes retention of sodium and loss of potassium; this will hold water in the body and cause an increase in BP
What is a modified form of cholesterol used for Vit. D synthesis?

What does it require to carry on the Vit. D pathway?
7-Dehydrocholesterol

UV light
in Vit. D synthesis pathway, breakdown of 7-dehydrocholesterol produces what?
Vit. D3...AKA cholecalciferol
in Vit. D synthesis pathway, what is formed from cholecalfierol (Vit. D3) and where in the body does this happen?

what enzyme is used to make this product?
25-hydroxycholecalciferol in the liver

25-hydroxylase
in Vit. D synthesis pathway, what is produced from 25-hydroxycholecalciferol?
Where does this occur and what enzyme is used?
1,25-dihydroxycholecalciferol in the kidneys

used 1α-hydroxylase AND PTH
What is the active form of Vit. D in the body?
1,25-dihydroxycholecalciferol
Congenital adrenal hyperplasia is caused by an increase in what?
increase in androstenodione...causes too many sex hormones in the adrenal cortex due to decreased cortisol and increased ACTH
Genetic deletion of what specific enzyme can cause congenital adrenal hyperplasia?
CYP21 (responsible for making aldosterone and cortisol); The pathway is devoted entirely to making androstenedione
What are the most common clinical signs and symptoms of vitamin D deficiency?
mental retardation and developmental delays

Very high PTH, low calcium levels
Increase of vitamin D causes an increase or decrease of calcium? What about phosphorus?
Increase in both.

Remember that vitamin D pathway needs PTH, which releases phosphorus
Poly and dissacharides get converted to their component monosaccharides in the digestrive tract by what enzyme?
glucosidases
What happens to undigested poly/disaccharides?
get fermented by INTESTINAL BACTERIA and excreted
Lactase breaks down what into what?
breaks down lactose into glucose and galactose
If the body can't break down lactose, what happens to it?
lactose gets fermented to lactic acid, methane and hydrogen gasses
What is the glycemic index?
how fast blood glucose levels rise after eating a certain food
How are monosaccharides transported into tissues?
using GLUT transporters
Explain the role of GLUT1
highly expressed in RBC and has high affinity (low Km) for glucose
Explain the role of GLUT2
in the LIVER...low affinity
Explain the role of GLUT3
in the BRAIN...high affinity
Explain the role of GLUT4
insulin sensitive...expressed in adipose and skeletal muscles
Where is pyruvate carboxylase found and not found?
Found in mitochondria of liver and kidney cells, not found in mitochondria of muscle
Describe the structure of the GLUT receptors
all contain 12-membrane spanning domains
Does diabetes increase AGEs?

How about oxidizing agents?
yes and yes
Explain Type I diabetes
body doesn't make insulin
Explain Type II diabetes
body is resistant to it's own insulin
Does ammonia increase or decrease the blood pH?
increase (NH4+ = basic)
What molecule can alter redox balance reactions, protein structure/function and inhibit ox. phos by disrupting the H+ gradient?
ammonia
Positive N balance commonly occurs when?
childhood or pregnancy
Negative N balance commonly occurs when?
dietary deficiency
catabolic stressors (infection)
In the urea cycle pathway, the reaction catalyzed by OTC produces what?
citruline and Pi
How many nitrogens are needed for the urea cycle and where do they/it comes from?
two nitrogens

one N is in the mitrochondria in the liver; the other N comes from Aspartate in the cytosol
What are the products of the urea cycle?
arginine, fumurate and urea
Which compound is regenerated in the urea cycle?

What happens to it?
ornithine

travels back to mitochondria where OTC uses it to make more cituline and Pi
Is the urea cycle reversible?
NO
What is the rate limiting step in the Urea cycle (include the substrates, products and enzyme involved)
starting: HCO3 + NH4+
product: carbamoyl phosphate
enzyme: CPS1
Is the urea cycle induced or supressed by high protein diets or prolonged fasted?
induced
What stimulates the rate-liming enzyme in the urea cycle pathway?

What makes the molecule?
NAG

NAG is made from acetyl CoA and glutamate
Once urea is made, where can it go?
kidneys to be excreted
intestine to be cleaved by bacteria
What is BUN and what is its function?
blood urea nitrogen

checks for kidney and liver function
Explain which of these will increase or decrease BUN:
Kidney failure
High protein
Malnutrition
Liver failure
Overhydration
Kidney failure = increase
High protein = increase
Malnutrition = increase
Liver failure = decrease
Overhydration = decrease
Acquired hyperammonemia is caused by what?
liver disease (maybe others)
Name the 2nd most common urea cycle disorder
OTC deficiency (hereditary and X-LINKED!)
Transamination is catalyzed by what?
aminotransferases (AKA transaminases)
An amino acid gives its amino group to alpha-KG to produce what?
glutamate
What cofactor do transaminases need?
PLP
Where does PLP come from and why is it needed?
PLP is made in the liver from Vit. B6

PLP is a cofactor for transaminases and deamination rxns
After glutamate has picked up an ammonia, where does it go?
Goes to the liver to decompose into alpha-KG and ammonia
What reaction is catalyzed by ALT?
pyruvate + glutamate --> alanine + alpha-KG
What reaction is catalyzed by AST?
OAA to asparate and asparagine
What's the function of glutamate dehydrogenase?
used to deaminate glutamate to alpha-KG and free ammonia in the liver and kidney
All AA reactions that undergo transamination reactions produce ___________
glutamate
Explain what glutaminase does
converts glutamine to glutamate + NH4 in the LIVER
Explain what glutamine synthase does
converts glutamate + NH4 to glutamine in the CYTOSOL
What molecule can bring to two ammonias to the liver?
glutamine
Are transamination rxn's reversible?
YES
What molecule other than glutamine and glutamate can carry ammonia to the liver?
alanine (from pyruvate)
In the liver, alanine + alpha-KG breakdown into what?

What enzyme catalyzes this?
pyruvate+glutamate

ALT! (think ALT when alanine and pyruvate are involved)
Glucogenic AA are degraded to what?
pyruvate or TCA cycle intermediates (to run gluconeo)
Ketogenic AA are degraded to what?
acetyl coA or acetoacetate (to make ketones or make FA)
Which AA (ketogenic, glucogenic or both) can be stored as fat?
ketogenic
Does insulin promote or reduce dietary AA uptake and protein synthesis?
promotes
Which hormone stimulates ubiquitin synthesis?
cortisol
Does cortisol stimulate AA uptake in the liver?
YES
Does cortisol stimulate glycolysis or gluconeo?
gluconeo
Explain the role of AA in muscles and liver in a fasted state
muscle is a major source of AA

liver uses a lot of AA
What is a hypercatabolic state?
Will there be negative or positive nitrogen balance?
What mediates this type of state?
state of increased fuel usage

negative N balance

cortisol is an important mediator
What are two possible sources of essential amino acids?
Diet or from protein turnover

(you're body can't synthesize it from scratch)
What AA is made from phenylalanine?
tyrosine
The synthesis of cysteine requires what AA? WHY?
methionine

cysteine gets its S (sulfur) from methionine
What are tetrahydrofolate and tetrahydrobiopterin (BH4) used for?
cofactors in AA synthesis
The cofactor BH4 (tetrahydrobiopterin) is used for what AA rxn?
phenylalanine --> tyrosine
Maple syrup urine disease
presence of LEUCINE (essential AA acid) in the blood

tx - give branched AA
Phenylketonuria
deficiency in phenylalanine hydroxylase (does phenylalanine --> tyrosine)
accumulation of phenylalanine
deficiency in tyrosine
What enzyme makes tyrosine?
phenylalanine hydroxylase
Albinism
caused by tyrosinase deficiency, which makes melanin (tyrosine-->dopa-->melanin)
What enzyme makes melanin?
tyrosinase
Hyperhomocystinemia
cystathionine synthase deficiency

highly elevated homocysteine in urine/blood & increase methionine

tx - B6, B12, folate and methionine restriction
Alkaptonuria
homogentisate oxidase deficiency

homogentisate accumulates (causes dark urine)

must restrict phenylalanine and tyrosine in diet
What's the starting material for KB synthesis?
acetyl coA
In a 1-2 day fast, where are ketone bodies imported to?
heart, kidneys & skeletal mm
In what body organ does KB synthesis take place?
liver
Why does the liver make excess acetyl coA for KB synthesis?
in fasted state, a lot of oxaloacetate is sent for gluconeo...which limits TCA activity and excess Acetyl CoA
What does the liver obtain from B-ox of excess FA?
NADH & FADH2 (w/o involvement of TCA cycle, which can go and make energy directly via ox.phos)
What is beta-hydroxybutyrate?
Ketone bodies
What is acetoacetate and what can it produce?
It's a compound in the KB synthesis pathway.
Produces beta-hydroxybutyrate AND acetone
What enzyme in the KB synthesis forms acetoacetate?
b-hydroxybuterate dehydrogenase
What enzyme in the KB synthesis forms acetoacetyl coA?

What's the starting compound?
succynil CoA

acetoacetate
In ketoacidosis, which compounds will be elevated?
beta-hydroxybyterate and acetoacetate (+ acetone)
All AA and carbs are converted to what before the start of FA synth?

how many carbons long is this?
citrate (6C)
In the FA synthesis pathway, where does citrate travel to begin it's breakdown?
cytosol
In the FA synthesis pathway, what enzyme breaks down citrate? What molecules form from this rxn?
citrate lyase

OAA and Acetyl CoA
In the FA synthesis pathway, once OAA is formed in the cytosol, where does it go?
converted to malate (via MDH), then malate gets converted to pyruvate (via malic enzyme). Pyruvate goes to the mitichon.
In the FA synthesis pathway, what enzyme forms pyruvate in the cytosol?
malic enzyme (malate --> pyruvate)
In the FA synthesis pathway, where is an NADPH produced?
malic enzyme reaction (malate --> pyruvate)
In the FA synthesis pathway, what is the RLS?
Acetyl CoA carboxylase
In the FA synthesis pathway, once Acetyl CoA is made from citrate, what happens to it?
acetyl coA --> malonyl coA --> palmitate
Where does FA synthesis take place?
hepatic cytosol
In the FA synthesis pathway, what enzyme forms palmitate?
FA Synthase
Explain the final structure of FA synthesis
palmitate - saturated 16C chain
In the FA synthesis pathway, what molecule acts as the start of the FA chain to which other carbons bind?
acetyl CoA
How many carbons of the malonyl coA actually attach to the growing FA chain?
2 of the 3

the third is needed for acetyl coA carboxylase (RLS) regulation
In the FA synthesis pathway, what 2 places/rxns provide the NADPH needed to run this rxn?
malic enzyme
PPP
Palmitate can be elongated up to ___ carbons and desaturated up to carbon ___
24 carbons long

up to the 9th carbon in the chain
Name the 2 essential 18C FA needed by your body
linoleate (C18:2@9,12)

linolenate (C18:3@9,12,15)
Arachidonate, is NOT an essential FA because it can be made in the body from ____________
linoleate
Does the rise of NADH inhibit the TCA cycle?
yes, it feedback inhibits isocitrate dehydrogenase (RLS)
Are citrate lyase, acetyl coA carboxylase and malic enzyme inhibited or induced by insulin?
induced
What transport protein is inhibited by malonyl coA to prevent fatty acyl transfer back into the mitrochondria and needlesly run B-ox?
carnitine
What feedback inhibits the RLS of FA synthesis?
palmitoyl coA feedback inhibits acetyl coA carboxylase
Does insulin control the availibility of Glyc-3-P?
YES
In the formation of TG from fatty acids in adipose tissue, what process can you run to form Glyc-3-P?
ONLY glycolysis (forms DHAP --> glyc-3-p)
In the formation of TG from fatty acids in the liver, what process can you run to form Glyc-3-P?
glycolysis (forms DHAP --> glyc-3-p) AND glycerol (glycerol --> glyc-3-p)
SAM is formed from what?

What is it used for?
methionine

methyl donor in synthesis of creatine, neurotransmitters and methylation of DNA
Why is folate needed for B12?
donates a carbon group to B12 so it can then go on to convert homocysteine to methionine
Explain how folate is absorbed
All glu resides are cleaved except ONE; DHFR enzyme is used to reduce folate to tetrahydrofolate (FH4)
What enzyme is needed to reduce folate?
DHFR (dihydrofolate reductase)
What is the primary carbon source used to donate carbons to folate?
serine
What are folates with carbon called?
one-carbon pool
Folate deficiency affects what?
Purine and dTMP synthesis (and thys DNA synth and replic)
Serine synthesis (needed to donate carbons to folate)
methylcobalamin synthesis (Met-B12)
What is cobalamin? what is in the middle of its structure?

how is it made?
Vit B12 - cobalt in the middle

made by bacteria after eating food
Cyanocobalamin is a form of _______ found mainly in _____________.
Form of Vit. B12 found in supplements (not found in nature)
After ingestion, B12 is converted to what 2 forms?
methyl cobalamin

deoxyadenosylcobalamin
What is haptocorrin (TC I) used for?
transports B12 to the gut from the the GI tract
What removes heptocorrin (TC I) from B12?

Once the TCI is off, what happens to B12?
pancreatic enzymes

Bare B12 is then bound by Intrinsic Factor (IF) and enters the enterocytes in the small intestine; IF is released once B12 is absorbed
Explain what TCI and TCII do
Haptocorrin (TCI) carries the B12 from the stomach to the duodenum, where it is broken up by pancreatic proteases.

TCII binds B12 in the enterocytes once released by IF and takes it to TCII receptors in cells that need B12
Once B12 is absorbed, what takes it to cells in the body that need B12?
TCII --> goes to TCII receptors
Name the 2 reactions we learned that require B12, and what main enzymes are needed in each.
1) methylation of homocysteine to form methionine (Met-B12 enzyme)

2) conversion of methylmalonyl-CoA to Succinyl CoA (via adenosyl-B12 enzyme)
Which rxn is affected in folate deficiency...one using Met-B12 or one using adenosyl-B12?
Met-B12 (met synthase + B12)
If there is a folate deficiency, what would build up in the Met-B12 rxn?
homocysteine build up
SAM donates what to things like creatine, epinephrin, neurotransmiters, etc?
METHYL groups
Does DNA methylation cause gene silincing?
YES
Can alterations in SAM levels alter gene expressions?
YES
Hyperhomocysteinemia is associated with what disease?
cardiovascular disease
Name some things that can cause hyperhomocysteinemia (increased homocysteinemia)
Met synthase deficiency
MTHFR deficiency
cystathionine synthase mutations
B12 deficiency
Folate deficiency
B6 (makes PLP) deficiency
Excess SAM suppliments
How do you fix hyperhomocysteinemia?
giving B6, B12, folate suppliments

Also choline and betaine (these two can make take methionine from homocysteine in the LIVER, WITHOUT needing B12)
What is macrocytic anemia
larger than normal RBC (but fewer in number)
- due to Vit B12 and folate deficiencies
Causes neurological symptoms like thingling in extremities
Is N5-CH3-FH4 the most stable form of folate?

Is it the most functional form?
YES

NO
N5-CH3-FH4 donates a methyl group to what to become FH4?
B12
What is the most functional form of Folate (one that can be used by the body)?
FH4 (tetrahydrofolate)
In the trap hypothesis, which compound builds up? (N5-CH3-FH4, FH4, B12 of Met synthase?)
N5-CH3-FH4
Deficiency in what two things can cause the trap hypothesis?
B12 and folate deficiency
If you have a B12 deficiency can you make methionine?

Can you make SAM?
NO

NO
Why does a deficiency in B12 and folate cause a deficiency in certain neurotransmitters?
B12 and Folate are needed to turn homocystein to methionine. Methionine is then needed to make SAM, which goes on to donate a methyl group in rxn's synthesizing neurotransmitters
What disease do you have if you don't make enough IF?
pernicious anemia (not enough IF to transport B12 across intestinal wall)
What causes B12 malabsorptions?
lack of proteases or TCI
If there is less gastric acid and IF present, what form of B12 can you take still?
the cyanocobalamin form (found in supplements)
Does less acid in the GI also mean there is less intrinsic factor?
YES
Do elevated MCV (mean corpuscular volume) suggest macrocytic anemia?
YES
In B12 and folate deficiencies, would there be elevated homocysteine and methylmalonic acid levels in serum?
YES

(methylmalonic acid does not need folate)
A deficiency in folate will not cause a rise in which of these in the serum: homocysteine or methylmalonic acid?
methylmalonic acid
Reduced acid or IF secretions resulting in less B12 freed from haptocorrin, commonly affects which people?
aged folks
In older people, you may see what in the absence of anemia?
neurological symptoms
Contracting skeletal mm uses what to make ATP?

is this process aerobic?
glycolysis

initially anaerobic and then becomes aerobic
Muscle contractions that occur for over an hour use what for energy?
B-oxidation
After anaerobic glycolysis makes lactate, explain what happens to it in fed and fasted states?

What happens if lactate can't get out of the cell>
Fed - energy or FA synthesis

Fasted - turned to pyruvate for gluconeo

decreases cell pH
In the fasted state, skeletal muscle can use what for energy?
FA and KB
Name the 3 sources of energy that skeletal mm can use until sufficient glycolysis can occur?
creatine phosphate
myokinase (2ADP-->1ATP + 1AMP)
myosin hydrolysis of ATP
What receptors does skeletal mm use to import body-wide glucose?

Is skeletal mm insulin dependent?
GLUT4 (insulin dependent)

yes
Can females use more B-ox in fasted state than males?
YES
What replenishes the skeletal muscles own glycogen supply after a contraction?
blood glucose levels
With type I diabetics, a sudden increase in exercise will cause hypoglycemia or hyperglycemia?
hypoglycemia
With type I diabetics, a sudden decrease in exercise will cause hypoglycemia or hyperglycemia?
hyperglycemia
What are the starting material for alcohol metabolism?
ethanol and NAD+
What is the toxic intermediate in alcohol synthesis? What is the final product of alcohol metabolism?
acetylaldehyde is toxic

acetate is the final product
In alcohol metabolism, does the MEOS system produce NADH?
NO

it oxidizes NADPH to NADP+
In alcohol metabolism, where in the cell does the MEOS system take place?
in the ER by using the Cyt P450 enzyme called CYP2E1
Which has a higher Km for alcohol, CYP2E1 or ADH?
CYP2E1 has a higher Km...only binds alcohol when there is a lot present
If the liver can't use the acetate made from alcohol metabolism, where does the acetate go?
exported to extrahepatic cells, made into acetyl CoA and catabolized in TCA in those cells
Which organs in the body can use a lot of acetate from alcohol metabolism?
skeletal mm, heart, kidneys
Explain the difference between ADH1, ADH2 and ADH 4
ADH1 and ADH2 are both in the liver (ADH1 has lower Km than ADH2)

ADH4 occurs in the GI
Explain the difference between ALDH1 and ALDH2
ALDH1 is found in hepatic cytosol

ALDH2 is found in hepatic mitochondria (lower Km than ALDH1)
In alcohol metabolism, why do NADH levels build up?
because the alcohol metabolism enzymes such as ADH/CYP2E1/ALDH ARE NOT regulated by NADH levels.....as long as the pt is drinking alcohol, the pathway will be active, meaning NADH will be made.

OX. PHOS. IS regulated by NADH...it can't process all the NADH from alc. met., so NADH builds up
Say which of these will be increased or decreased due to high NADH levels:
TCA cycle
B-ox
glycolysis
gly-3-p synth
pyruvate --> lactate
OAA --> malate
TCA cycle = decrease
B-ox = decrease
glycolysis = decrease
glycerol-3-p synth = increase
pyruvate --> lactate = increase
OAA --> malate = increase
A fatty liver is caused by an increase TG or FA?
TG
How does an increase in NADH cause ketoacidosis?
decrease in TCA causes an increase in ACETYL CoA; This is then made in KETONE BODIES. The heart and kidneys would rather use the excess acetate in the body and not ketones, so ketoacidosis results
Gout results because what competes with uric acid?
lactate competes with uric acid, causing excess uric acid build up. (and also due to ketoacidosis)

(increase in ethanol leads to increased pyruvate --> lactate. Lactate acidosis results, which competes with uric acid for excretion)
How can hypoglycemia results in an alcoholic in a fasted state?
ethanol causes pyruvate to be turned to lactate because less; less pyruvate is available for gluconeo = hypoglycemia
In heavy drinkers, how can hyperglycemia occur in a fed state?
ethanol causes a rise in NADH, which inhibits glycolysis. Can't breakdown glucose in the blood = hyperglycemia
In heavy drinking, what can acetaldehyde bind to and cause problems?
amino acids
In heavy drinking, what does acetaldehyde do in terms of protein synthesis and glutathione?
decrease protein synthesis = decrease in apoproteins = decrease in lipoprotein synth.

decrease in glutathione = increase in free radicals
In liver injury (due do drinking or other reasons), which of these will increase or decrease?

VLDL secretion
protein synthesis
acetate
acetaldehyde
ALT/AST in blood
VLDL secretion = decrease (=fatty liver)
protein synthesis = decrease
acetate = decrease
acetaldehyde = INCREASE (toxic stuff)
ALT/AST in blood (increase)