biochem exam 4/8/24 Flashcards
1
Q
the more active form of glutamine synthetase is the
- adenylylated form of the enzyme
- de-adenylylated form of the enzyme
A
- de-adenylylated form of the enzyme
2
Q
PII is the factor that binds to adenylyl transferase (AT). If PII is uridylylated
- AT preferentially catalyzes the adenylation of glutamine synthetase (GS)
- AT preferentially catalyzes the de-adenylation of GS
A
- AT preferentially catalyzes the de-adenylation of GS
3
Q
An elevated glutamine concentration leads to…
A. An increase in the [PII + UMP]
B. A decrease in the [PII + UMP]
C. The de-adenylation of glutamine synthetase
A
B. A decrease in the [PII + UMP]
4
Q
When there is a sufficient amount (or more) of gln in a cell, which of the following is true about glutamine synthetase and the associated regulatory enzyme
- AT-PII will be uridylylated, GS will not be adenylylated and GS will be active
- AT-PII will be uridylylated, GS will be adenylylated and GS will be inactive
- AT-PII will not be uridylylated, GS will be adenylylated and GS will be inactive
- AT-PII will not be uridylylated, GS will not be adenylylated and GS will be active
A
- AT-PII will not be uridylylated, GS will be adenylylated and GS will be inactive
5
Q
heme is derived from ____ and is broken down to form ____
- arginine, creatine
- glycine, creatine
- glycine, bilirubin
- blirubin, creatine
A
- glycine, bilirubin
6
Q
Which of the following statements is incorrect?
A. GABA is derived from glutamate
B. Histamine→histidine
C. Serotonin→tryptophan
D. Dopamine→tryptophan
E. Epinephrine→tyrosine
A
D. Dopamine→tryptophan
7
Q
therapies for Parkinson’s disease include
- block formation of L-Dopa
- administer L-dopa to the patient
- accelerate dopamine breakdown
- administer an MAO inhibitor
A
- administer L-dopa to the patient
- administer an MAO inhibitor
8
Q
which of the following reactions is part of the normal nucleotide synthesis
- AMP to dAMP
- GDP to dGDP
- TDP to dTDP
- UTP to dUTP
- CMP to CDP
A
- GDP to dGDP
9
Q
Folate and/or vitamin B12 is/are required for the synthesis of…
A. dAMP
B. dCMP
C. dGMP
D. dTMP
E. dUMP
A
D. dTMP
10
Q
which statement is false
- gout involves uric acid crystals in joints
- purine catabolism leads to uric acid formation
- allopurinol inhibits uric acid breakdown
- allopurinol inhibits xanthine oxidase
A
- allopurinol inhibits uric acid breakdown
11
Q
which of the following inhibits the reduction of NDPs to dNDPs
- allopurinol indomethacin
- azaserin, acivicin
- aminopterin, methotrexate
- gemcitabine
A
- gemcitabine
12
Q
which of the following are Gln analogs that interfere with nucleotide synthase
- allopurinol indomethacin
- azaserin, acivicin
- aminopterin, methotrexate
- gemcitabine
A
- azaserin, acivicin
13
Q
aminopterin, methotrexate, and fluorouracil reduce the synthesis of
- glutamate
- glutamine
- cAMP
- dAMP
- dTMP
A
- dTMP
14
Q
Sources of Nitrogen
A
Ammonia is toxic to mammalian cells and must be immediately used up (assimilated) or converted to urea and removed (Ch 18)
Soluble, biologically useful nitrogen-containing molecules are generally scarce, so organisms are conservative in their use
Ammonia is assimilated into glutamine (major) and glutamate (minor) in mammalian cells.
Glutamine and glutamate are the nitrogen sources for the cellular synthesis of other amino acids and other nitrogenous compounds.
15
Q
Assimilation of Ammonia into Glutamine (Major Pathway)
A
Glutamate + glutamine synthetase = acyl-phosphate intermediate
Glutamine is the source of amino groups for most other nitrogenous compounds.
16
Q
Major Source of Glutamate
A
Breakdown of excess dietary amino acids by transamination reactions yields high levels of cellular glutamate, shortly after the meal is consumed.
Glutamate is the source of amino groups for most other amino acids.
17
Q
Assimilation of Ammonia into Glutamate (Minor Pathway)
A
Km for NH4+ = 1 mM rendering glutamate synthesis only possible when [NH4+] is abnormally high (hyperammonemia).
In cells, both Glutamine and Glutamate are kept at concentrations higher than other amino acids
18
Q
Allosteric Regulation of Glutamine Synthetase
A
Each molecule alone partially inhibits the enzyme…
6 of these are derived from glutamine
If all products are present at sufficiently high levels, the enzyme is essentially turned off.
Don’t need it, don’t make it.
19
Q
Covalent Regulation of Glutamine Synthetase
A
GS + AMP = OFF
GS = ON
PII + UMP + AT = GS ON (via deadenylation)
PII + AT = GS + AMP = OFF (via adenylation)
20
Q
Simplified: Covalent Regulation of Glutamine Synthetase
A
high ATP or high alpha ketoglutarate, low Gln
- AT-PII uridylyated - yes
- GS adenylylated - no
- GS active - yes
low ATP or low alpha-ketoglutarate or high Gln
- AT-PII uridylyated - no
- GS adenylylated - yes
- GS active - no
21
Q
Essential and Non-Essential Amino Acids
A
Essential Amino Acids:
- Amino acids that cannot be synthesized (made) by an organism and must be a component of the diet.
Non-Essential Amino Acids:
- Amino acids that can be synthesized by an organism and are not required to be a component of the diet.
22
Q
Amino Acid Synthesis
A
Synthesized from 6 common precursors!
- Sometimes more than one way…
We’ve seen some of these already:
Phenylalanine→Tyrosine (PKU) Pyruvate→Alanine (Muscle) Oxaloacetate→Aspartate (Urea Cycle) α-KG → Glutamate (Transamination) Glutamate→Glutamine (Above)
Connections:
Serine→Glycine uses THF (remember?!) Methionine cycle involves SAM, B12, Folate (B9)!
Glycolysis, PPP, CAC, AA Catabolism, etc.
23
Q
Porphyrins (Heme)
A
Heme isn’t just for hemoglobin:
Myoglobin, catalase, peroxidase, P450 liver cytochromes
Deficiency in the enzymes in this pathway cause a build-up of toxic porphyrins→ Porphyria
“Mad” King George III
Genetic, can be triggered by meds Different porphyrias, different symptoms Neurological, skin, photosensitivity
24
Q
heme breakdown
A
to bilirubin etc.
a stronger antioxidant, but an elevated level in blood may indicate liver disease
heme breakdown color: black/blue/purple
biliverdin breakdown color:
green
bilirubin breakdown in blood:
yellow
25
creatine from Gly, Arg, Met
a ready source of phosphoryl groups for quick synthesis of ATP (phosphocreatine s later replenished by phosphoryl transfer from ATP)
ADP + PCr = ATP + Cr
delta G = -12.5kJ/mol
26
Neurotransmitters: Derived from Amino Acids
dopamine, norepinephrine, epinephrine
gamma-aminobutyric acid (butyrate) - GABA
serotonin
histamine
nitric oxide (NO)
27
From tyrosine:
dopamine, norepinephrine, epinephrine
catecholamines
tyrosine -
deficiency of this coenzyme results in deficiency of catecholamines as well as PKU
dopamine -
too little: associated with Parkinson's
norepinephrine
regulates blood pressure
epinephrine
fight or flight
28
Therapy for Parkinson’s Disease
raise dopamine levels (L-dopa)
maintain dopamine levels by inhibiting monoamine oxidase (MAO inhibitors, such as selegiline)
- xadago (safinamide)
L-dopa is the precursor to dopamine
L-dopa crosses the BBB, dopamine cannot
can be metabolized in the periphery
challenge:
must get L-dopa to the brain without being metabolized
if you do not beat this challenge
1. side effects
2. reduced availability of DOPA in the brain
solution
- co-administer with a DOPA carboxylase inhibitor so that the drug isn't metabolized to DOPA in the periphery, and therefore more DOPA gets to the brain
29
from glutamate
GABA
1. astrocytes control the biosynthesis and turnover of glutamate and GABA
2. there are other ways to treat epilepsy - not just through GABA
3. can be co-released with glycine (also inhibitory; AA)
lack associated with epileptic seizures.
treatment: administer GABA analogs or inhibitor breakdown
30
from tryptophan
serotonin
- suppresses appetite
- induces fatigue
- makes you mellow
brainstem control of respiration
serotonin syndrome: DDI
Trp is also a precursor of melatonin which is involved in the control of circadian rhythms
tetrahydrobiopterin
- deficiency of this coenzyme results in deficiency of serotonin and PKU
Monoamine oxidase
- maintains serotonin levels
31
from histidine
histamine
released in allergic response and stimulates acid secretion in the stomach
this structural analog interferes with the action of histamines (an H2 receptor antagonist used to treat gastric reflux)
32
from arginine
nitric oxide
involved in neurotransmission, blood clotting, control of blood pressure
gas
activates GC to cGMP for vasodilation
33
De Novo (From Scratch) Nucleotide Synthesis
NMPs are synthesized "on phosphorizes" not by adding free bases to ribose
Ribose + P to P-ribose to NMP
not by attaching a pre-formed base to P-Ribose
basically
- start with the P-ribose and synthesize the rest of the P-Ribose
34
purine nucleotide synthesis
35
Purine Nucleotide Synthesis: Salvage Pathway
Some tissues can’t De novo, so when RNA/DNA degenerates, bases and nucleosides can be recovered, and recycled back into nucleotides.
adenine + PRPP to adenylyase PPi
enzyme: adenine phosphoribosyltransferase
hypoxanthine + PRPP to inosinate + PPi
guanine + PRPP to guanlyate + PPi
enzyme: hypoxanthine-guanine...
36
Nucleotide Synthesis
general scheme:
nucleotide synthesis
start mono
add phosphates
Ribose → deoxyribose via reduction
37
folate, vtamine/coenzyme B12 & DNA synthesis
folate & B12 required for DNA synthesis
38
B12 and or folate deficiency
one serious consequence of B12 or folate deficiency as N5, N10-Me THF defc. dTMP def. and reduced DNA synthesis
39
Nucleotide Degradation
purine nucleotides to urc acd to excretion
pyrimidine nucleotides to NH4 to ureaa to excretion
40
Excessive Purine Catabolism
Following excessive purine consumption or synthesis
If this happens→overproduction of uric acid→ high [uric acid] in the blood and tissues...
Then urate crystals (the salt of uric acid) get deposited in the joints which become inflamed, painful, and arthritic. Additional deposits found in the kidneys
* The above are signs of Gout.
Cause unknown, maybe genetic?
90% of affected individuals are
men > 40 years old
* Effects ~ 1 million Americans
* Joint of big toe affected ~ 50% of cases
41
Gout
control of Gout:
Limit intake of foods rich in purines: meat (esp: liver), poultry, seafood
Avoid: alcohol, fructose-sweetened drinks, and obesity (these increase risk)
Vitamin C, dairy products, and coffee (not tea) may reduce risk
* Treatment for Gout
Allopurinol – an irreversible inhibitor of xanthine oxidase – the enzyme that converts purines to uric acid
Allopurinol therapy results in the accumulation of xanthine and hypoxanthine (instead of uric acid/urate), which are soluble (uric acid is not)
Other drugs you might see: Probenecid, Febuxostat
Treat pain/inflammation with NSAIDs, steroids, colchicine
42
Cancer
cancer cells are growing much more rapidly than most normal tissues, and have a great need for nucleotides, precursors of DNA & RNA
a growing array of anti-cancer drugs interfere with nucleotide biosynthesis:
- glutamine analogs - glutamine to source for nucleotides
- inhibition of ribonucleotide reductase - ribose to deoxyribose
- thymidylate synthesis blockers - need T's
43
Glutamine Analogs
Looks like glutamine, but isn’t. Interferes with enzymatic reactions involving glutamine and the formation of nucleotides
Gln is a nitrogen donor in many nucleotide synthesis rxns
mechanisms unclear: competitive or suicide inhibition
research only
44
Ribonucleotide Reductase Inhibition
gemcitabine seems to do that
45
Blocking dTMP Synthesis
use fluorouracil on dUMP
46
Resting muscle derives most of its energy from...?
A. Muscle glycogen
B. Fatty acids
C. Blood glucose
D. Phosphocreatine
47
the cori cycle involves the transport of ____ from muscle tissue to the liver and of _____ from the liver to muscle
1. glucose, glutamine
2. alanine, glucose
3. lactose, glucose
4. glucose, lactate
5. lactate, glucose
5. lactate, glucose
48
Which of the following carries out only aerobic metabolism and therefore must have access to oxygen (O2)?
A. Liver
B. Adipose tissue
C. Skeletal muscle
D. Cardiac muscle
E. Brain
49
which of the following normally uses
only glucose as a source of energy
1. the liver
2. adipose tissue
3. skeletal muscle
4. cardiac muscle
5. the brain
5. the brain
50
which of the following (types of) hormones is relatively fast-acting
1. catecholamines
2. vitamin D
3. Eicosanoids
4. retinoids
5. steroids
1. catecholamines
3. Eicosanoids
51
an elevated level of insulin would lead to a(n) _____ in glucose synthesis in the liver
increase
decrease
decrease
52
an elevated level of glucagon would lead to a(n) in glycogen breakdown n the liver
increase
decrease
increase
53
An elevated level of cortisol would lead to a(n) ___ in fatty acid mobilization from adipose tissue.
A. Increase
B. Decrease
A. Increase
54
an elevated level of epinephrine would lead to a(n) ___ in glucose synthesis in the liver
increase
decrease
increase
55
an elevated level of epinephrine would lead to a(n) ___ in glucagon secretion
increase
decrease
increase
56
what effect will an elevated level of insulin have on (i) glycogen breakdown in the liver and muscle and on (ii) fatty acid synthesis in the liver
1. (i) promote (ii) promote
2. (i) promote (ii) inhibit
3. (i) inhibit (ii) promote
4. (i) inhibit (ii) inhibit
3. (i) inhibit (ii) promote
57
The TCA cycle is the central metabolic hub
AA carbon skeletons
Electron extractor
Building block and energy import/export
58
Subcellular locations of the major metabolic pathways
59
Specialized Functions of Tissues/Organs
liver
- processes fats, carbohydrates, and proteins from det; synthesizes and distributes lipids, ketone bodies, and glucose for other tissues; converts excess nitrogen to urea
brain
- transports ions to maintain membrane potential; integrates inputs from body and surroundings; sends signals to other organs
cardiac muscle
- uses ATP generated aerobically to pump blood
lymphatic system
- carries lipids from the intestine to the liver
adipose tissue
- synthesizes stores and mobilizes triacylglycerols. Brown adipose tissue carriers out thermogenesis
skeletal muscle
- uses ATP generated aerobically or anaerobically to do mechanical work
60
The Liver
The central metabolic organ; it transforms and exports/imports molecules.
Hepatocytes transform dietary nutrients into fuels and precursors required by other tissues.
Flexible: can adjust enzyme levels to adjust to nutritional state
Oxidative organ: detoxifies foreign organic compounds (Cytochrome P-450 and others)
Regenerates!
61
carbohydrate metabolism (liver)
fates of glucose 6-phos
1. glucose (blood)
2. glycogen
3. glycolysis to CAC
4. Glyc. to AcCoA to anabolism
5. pentose phosphate pathway
glucose to G-6-P
- free glucose (blood)
- liver glycogen (storage)
- energy via glycolysis and CAC
- acetyl-CoA - synthesis of larger molecules via glycolysis
- NADPH & nucleic acid precursors via the PPP
62
Amino acid metabolism
fates of AA's
1. protein (liver)
2. protein (elsewhere)
3. nucleotides etc.
4. deamination
A. urea
B. Pyruvate - glucose, acetyl-CoA
Amino acid users
1. protein synthesis in the liver
2. export to other tissues for protein
3. synthesis of nucleotide, hormones etc
4. deamination for:
a. gluconeogenesis
b. CAC to ATP
c. lipid synthesis
d. transformation into ammonia and urea
63
fatty acid metabolism
FA's are the primary fuel in the liver
fates of FA's
1. liver lipids
2. acetyl-CoA to CAC
a. CAC (energy)
b. ketone bodies
c. cholesterol etc
3. plasma lipoproteins
4. transport (free FA)
fatty acid uses:
1. storage in lipids (tails)
2. Major oxidative fuel for the liver (beta-oxidation to acetyl CoA to CAC)
3. transformation into ketone bodies, transported to other places
4. formation of cholesterol
5. incorporated into lipoproteins, transported to other places
6. combine with serum albumin, and transport to other places as a source of energy
64
Adipose Tissue
fatty acids cycle between TAGs and FFAs
2/3 of adipose tissue is TAGs
65
Skeletal Muscle
The source of energy depends on the activity level
1. At rest: source of energy comes from fatty acids (from adipose tissue) and ketone bodies (from the liver)
2. Moderate activity level: source of energy comes from FAs, KBs, AND glucose
3. Heavy activity level: source of energy comes from all of the above AND muscle glycogen (transformed into lactate) AND phosphocreatine
66
Time course of fuel consumption
creatine phosphate
anaerobic metabolism
ATP
67
the Cori cycle
how muscles use and replenish glycogen with the assistance of the liver
muscle: during heavy exercise, glycogen is broken down and anaerobic glycolysis leads to the formation of ATP and lactate
liver: rapid respiration produces ATP, which is used to form glucose from lactate in the liver
68
Heart Muscle and Brain
heart muscle
- completely aerobic
- mitochondria abundant (~50% of cell volume)
- fuel: FA's (main source), glucose, KB's phosphocreatine (minor source)
- lack of O2 fatal
brain
- normally uses only glucose, but can use KB's
- very active: accounts for 20% of O2 use when the body is at rest
69
types and classes of hormones
autocrine: acts on the same cells
paracrine: acts on adjacent cells
endocrine: acts on distant cells
1. Biosynthesis
2. Storage and Secretion
3. Transport
4. Binding
5. Relay and Amplification (cellular response)
6. Breakdown
70
Hormones
cell surface receptor
- peptide or amine hormone binds to a receptor on the outside of the cell; acts through the receptor without entering the cell
nuclease receptor
- steroid or thyroid hormone enters the cell; hormone-receptor complex acts in the nucleus
71
Hormones
plasma membrane receptors; relatively fast-acting
Peptide Hormones
3-200+ amino acids in length
Pancreatic: insulin, glucagon, somatostatin – growth hormone inhibiting hormone – GHIH)
Thyroid: calcitonin (calcium homeostasis and metabolism)
All hypothalamic and pituitary hormones
Catecholamine Hormones
Tyrosine (precursor)
→ L-DOPA
→ Dopamine
→ Norepinephrine
→ Epinephrine (Chapter 22)
Eicosanoid Hormones
72
Hormones
steroid hormones:
cholesterol to progesterone to cortisol or aldosterone or testosterone
Vitamin D
calcium homeostasis and metabolism to
7-dehydrocholesterol + UV light to vitamin D3 to 25-hydroxycholecaliiferol to 1,25-dihydroxycholecalciferol
Retinoid Hormones
Embryonic Development, Vision
beta carotene to vitamin A1 (retinol) to retinoic acid
73
Hormones
hormone regulation of fuel metabolism
peptides
- insulin (high blood glucose)
- glucagon (low blood glucose)
catecholamine
- epinephrine (stress; fast acting)
steroid
- cortisol (stress; slow acting)
thyroid hormones that regulate metabolism
74
Insulin
metabolic effect
75
Well-Fed State: Insulin and its Effects
76
Glucose and Insulin
more blood glucose leads to
- more insulin secretion
- less glucagon secretion
what makes this happen
- islet of Langerhanss
elevated [ATP] closes this channel, reducing K+ efflux and leading to...
77
ATP-Gated K+ Channel
remember
- normally elevated [ATP] closes this channel, leading to insulin secretion
type 2 diabetes treatment:
sulfonylurea drugs stimulate insulin secretion:
glyburide, glipizide, glimepiride
78
The fed state
Liver
- Glycogen synthesis
- Glycolysis
- Fatty acid synthesis
(-) glycogenolysis
(-) gluconeogenesis
(-) fatty acid oxidation
GLUT2
Glucokinase (hexokinase IV) Phosphorylase a to phosphorylase b
High F-2,6-BP Acetyl-CoA carboxylase
Muscle
GLUT4 to surface Glycogen synthesis
Adipose
GLUT4 to surface Synthesis of TAGs
79
The fasted state
Liver
glycogenolysis
Gluconeogenesis
(-) glycogen synthesis
(-) glycolysis
(-) acetyl-CoA carboxylase
Low F-2,6-BP
Muscle
Adipose
Breakdown of TAGs
80
Epinephrine (Fast)!
ready to fight or flee
81
Cortisol (Slow)!
released from the adrenal cortex in response to stress (long-term stress hormone)
acts slowly, increasing the fuel supply
increases the release of FAs from adipose and the synthesis of glucose, glycogen, and TAG in the liver. May result in weight gain
no evidence that supplements can lower weight by lowering [cortisol]
Glucocorticoid and stress hormone
In essence, this does the opposite of insulin
Cortisol is released in response to stress and low blood glucose
Hydrocortisone if used as a medication – is anti-inflammatory.
82
Starvation
Fed:
protein
- may be converted to fats (low efficiency)
carbohydrates
- maybe stored as glycogen
- maybe stored as fat (75% efficiency)
lipids
- maybe stored as a fat (95% efficiency)
starved
1. glycogen (liver & muscle) is depleted within ~12 hours
2. within ~24 hours, blood [glucose] begins to fall
- insulin secretion decreases
- glucagon secretion increases
3. these signal TAG mobilization & use
4. to provide fuel for the brain
83
Starvation
first 12-24 hours
- fatty acids to acetyl-CoA
- liver glycogen to glucose to acetyl-CoA max: ~12 hours
after glucose & glycogen are depleted:
- fatty acids to acetyl-CoA (continuing) no net conversion to glucose
- protein to AA's to pyruvate to glucose
- fat to ketone bodies to brain etc
- (fat to glycerol [from TAG's] to glucose
84
Starvation
liver
- glycogenolysis
gluconeogenesis
fatty acid oxidation
ketone body formation
amino acid oxidation
muscle
- fatty acid oxidation
- protein breakdown
adipose
- breakdown of TAGs
85
Regulation of Feeding Behavior
“-atide”, “-glutide” Trulicity, Ozempic, Rybelsus, Wegovy, Mounjaro
GLP-1 decreases blood glucose by enhancing the secretion of insulin.
It also decreases glucagon secretion.
And even increases taste sensitivity in the tongue (this is fun!).
This is great for diabetics!
Additionally, GLP-1 (and its agonists are pro-satiety)
→Weight loss! (shortage)
86
Summary of Hormonal Regulation
glycogen
- insulin: not broken down in muscle or liver but synthesized in muscles and liver
- glucagon: broken down in the liver, not synthesized in the liver
- epinephrine: broken down in muscle and liver, not synthesized in muscle and liver
- cortisol: *blank*
glucose
- insulin: not and liver, glucose uptake: done in muscle and liver
broken down in the liver, glycolysis: happens in the muscle and liver
- glucagon: synthesized in the liver, glycolysis does not take place in the liver
87
Major regulated steps
Glycolysis
hexokinase – P of glucose
PFK-1 – P of glucose-6-P
pyruvate kinase – phosphoenolpyruvate to pyruvate
Gluconeogenesis
pyruvate carboxylase - oxaloacetate phosphoenolpyruvate carboxykinase - PPEpyruvate fructose-1,6-bisphosphatase – removes PFK-1 P glucose-6-phosphatase – removes hexokinases P
Glycogen synthesis
glycogen synthase
Glycogenolysis
(phosphorylase kinase) glycogen phosphorylase
Pentose shunt
glucose-6-phosphate dehydrogenase – send it down the side path
88
Major regulated steps con’t
TCA cycle
(pyruvate dehydrogenase) isocitrate dehydrogenase a-ketoglutarate dehydrogenase
Oxidative phosphorylation
levels of ADP/ATP
Fatty acid oxidation
carnitine acyl transferase 1 – cytoplasm to matrix
Fatty acid biosynthesis
acetyl-CoA carboxylase – makes malonyl
Fatty acid storage
hormone-sensitive lipase
Urea cycle
carbamoyl phosphate synthetase-1
89
Key junction points
Glucose-6-phosphate
- glycogen synthesis/glycogenolysis glycolysis/gluconeogenesis
pentose phosphate shunt
Pyruvate
- to acetyl-CoA
- to oxaloacetate
- oxidation by TCA fatty acid synthesis gluconeogenesis
TCA cycle intermediate
Acetyl-CoA
- TCA cycle
fatty acid synthesis
ketone bodies
cholesterol, steroids, bile salts
Citrate
- TCA cycle
fatty acid synthesis
90
Regulation of fuel metabolism
Hormone
- Insulin
islet b cells
Release
- high glucose
Liver
- glycogenesis glycolysis FA synthesis
- glycogenolysis, gluconeogenesis
Muscle
- glucose uptake glycogenesis
Adipose
- glucose uptake
Counter-regulatory hormones
hormone
- Glucagon islet a cells
release
- low-glucose
liver
- glycogenolysis
- gluconeogenesis
epinephrine
- adrenal medulla
release
- acute stress
liver
- glycogenolysis
muscle
- glycogenolysis to lactate
adipose
- HSL
91
Key, direct actions of insulin
Glycolysis
- Stimulation: PFK-1 - via gene expression
pyruvate kinase - via gene expression PFK-2/FBPase-2 - via gene expression
Gluconeogenesis
- inhibition: PFK-2/FBPase-2
via gene expression
Glycogen synthesis
- Stimulation: glycogen synthase
Glycogenolysis
- inhibition: phosphorylase kinase glycogen phosphorylase
TCA cycle
- Stimulation: pyruvate dehydrogenase
Fatty acid oxidation
- inhibition: hormone-sensitive lipase
Fatty acid biosynthesis
- Stimulation: acetyl-CoA carboxylase
92
Key, direct actions of glucagon
Glycolysis
- Inhibition: PFK-1
(via PFK-2/FBPase-2)
pyruvate kinase
Gluconeogenesis
- Stimulation: fructose-1,6-bisphosphatase (via PFK-2/FBPase-2)
Glycogen synthesis
- inhibition: glycogen synthase
Glycogenolysis
- stimulation: phosphorylase kinase glycogen phosphorylase
TCA cycle
Fatty acid oxidation
- stimulation: hormone-sensitive lipase
Fatty acid biosynthesis
- inhibition: acetyl-CoA carboxylase
93
Key, direct actions of epinephrine
Glycogen synthesis
- inhibition: glycogen synthase
Glycogenolysis
- stimulation: phosphorylase kinase glycogen phosphorylase
TCA cycle
- stmulation: pyruvate dehydrogenase
(via Ca++ activation of phosphatase)
Fatty acid oxidation
- stimulation: hormone-sensitive lipase
Fatty acid biosynthesis
- inhibition: acetyl-CoA carboxylase
94
How many b.p.’s does a relaxed, closed circular piece of DNA with Lk = 100 have?
A. 100 B. 200 C. 1050 D. 1000 E. 2000
C. 1050
95
Increasing the Lk of this piece of DNA from 100 to 102 will lead to...
A. An increase in b.p.’s/turn and & negative supercoiling
B. Adecreaseinb.p.’s/turnand& negative supercoiling
C. Anincreaseinb.p.’s/turnand& positive supercoiling
D. A decrease in b.p.’s/turn and & positive supercoiling
D. A decrease in b.p.’s/turn and & positive supercoiling
96
if a piece of DNA has 12,600 bp's and a Lk of 1000 it is
underwound
relaxed
overwound
underwound
97
if a piece of DBA has 10500 bp's and an Lk of 1050 it will form
a negative supercoil
a positive supercoil
neither of the above; it will be relaxed
a positive supercoil
98
underwinding DNA may result in any of the following except
strand separation
increasing the Lk
negative supercoiling
cruciform DNA
increasing the Lk
99
which of the following inhibits bacterial topoisomerases
actinomycin D, acridine, and rifampicin
puromycin and tetracyclines
ciprofloxacin and levofloxacin
irinotecan and topotecan
ciprofloxacin and levofloxacin
100
camptothecin, irinotecan and topotecan inhibit
bacterial type I topoisomerase
bacterial type II topoisomerases
human type I topoisomerases
human type I topoisomerases
101
the typical error rate for DNA replication in E.coli after all proofreading is 1 in
100
10,000
1,000,000
10^7
10^9
10^9
102
which of the following inhibits both ribonucleotide reductase and DNA replication
cisplatin
oxaliplatin
gemcitabine
acridine
gemcitabine
103
gemcitabine inhibits
DNA synthesis
topoisomerase
RNA transcription
protein translation
DNA synthesis
104
Which of the following inhibits bacterial, but not human, RNA polymerase?
A. Actinomycin D
B. Acridine
C. Rifampicin
D. α-amantin
C. Rifampicin
105
the genetic material in the SARS-CoV2 virus is
DNA
RNA
the spike protein
the N protein
RNA
106
the Pfizer-BiioNTech and Moderna vaccines contain which of the following
RNA
DNA
the SARS-CoV2 spike protein
inactivated SARS-CoV2 virus
RNA
107
the typical error rate for protein translation is about 1 in
100
10,000
1,000,000
10^7
10^9
10,000
108
which of the following inhibits protein synthesis
actinomycin D, acridine, and rifampicin
puromycin and tetracyclines
tunicamycin
irinotecan and topotecan
puromycin and tetracyclines
109
Eukaryotic protein synthesis is inhibited by ___?
A. α-sarcin and ricin
B. Chloramphenicol and erythromycin
C. Clindamycin and streptomycin
D. Puromycin and tetracycline
A. α-sarcin and ricin
110
tunicamycin blocks
DNA replication
RNA Transcription
protein translation
protein glycosylation
reverse transcriptase
protein glycosylation
111
Most protein modification takes place in the ___?
A. Cytosol
B. Ribosome
C. Nucleus
D. Endoplasmic Reticulum
E. Mitochondria
D. Endoplasmic Reticulum
112
Diet Components
Nutrients
– Carbohydrates, lipids, protein (energy & more)
– Vitamins, minerals (no energy) – Water
Non-nutrients:
– Alcohol
– Phytochemicals (plant-derived, bio-active)
– Pigments
– Additives
113
Two “E”s
“Essential:” does not simply mean “necessary;” must be included in the diet
* Energy: energy stored in chemical bonds; molecules stored until energy is used:
– Carbohydrates: 4 kcal/g
– Protein: 4 kcal/g
– Fat (lipids): 9 kcal/g
– Alcohol: 7 kcal/g
114
Nutrients (narrowly defined)
* Vitamins: essential organic nutrients, required in small amounts; do not supply energy; may be degraded
* Minerals (metal ions): required for structure (Ca: bones & teeth) or function (Fe, Mg); indestructible
* Water: essential
115
Nutritional Standards
* American & Canadian standards (1997-): Dietary Reference Intakes (DRI)
* Age- and sex-specific
* Estimated Average Requirements (EAR)
* Recommended Dietary Allowances (RDA): supported by extensive research
* Adequate Intakes (AI): supported by some research
* Tolerable Upper Intake Levels (UL)
116
EAR and RDA Compared (1 of 2)
The Estimated Average Requirement (EAR) for a nutrient is the amount that meets the needs of about half of the population (shown here by the red line).
The Recommended Dietary Allowance (RDA) for a nutrient (shown here In green) is set well above the EAR. meeting the needs of about 99% of the population.
117
Recommended Intakes of Nutrients and Energy
nutrients
- enough for 99% of the subpopulation
energy
- average = RDA
118
Views of Nutrient Intakes
119
Notes about the DRI’s
* They apply to healthy people.
* For nutrients, remember 99%.
* Meant to apply to foods, not supplements
* Average requirements over time – OK to have ups and downs
* (We will discuss Daily Values later.)
120
Nutrition deficiency ... and assessment nutrition deficiency ... and assessment
beginning/cause
here is what is happening inside the body:
- primary deficiency caused by inadequate diet or secondary deficiency caused by problems inside the body
- declining nutrient stores
- abnormal functions inside the body
- physical (outward) signs and symptoms
how can the health care provider tell?
- diet history
- health history
- laboratory tests
- physical examination and anthropometric measures
121
Nutrition and Health
* Earlier, and in developing countries, disease
associated with deficiency: – Scurvy – Vitamin C
– Rickets – Vitamin D
* Today, in developed countries, chronic diseases often associated with excess:
– Heart disease (#1 cause of death in U.S.) – Cancers
– Stroke
– Diabetes
122
Healthy Diet (RPW, Chap. 2)
* General Principles: ABCD+V:
* Adequacy: enough of each nutrient & energy
* Balance: enough, but not too much, of each
* Calorie-control (& Energy Density)
* Nutrient Density (next 3 slides; g/kcal)
* Variety
123
Comparison: Nutrient & Energy
Density of Two Breakfast Options
nutrient-dense breakfast
- energy density: 500 kcal/450 g = 1.1
nutrient-poor breakfast
- energy density: 500 kcal/144 g = 3.5
nutrient density comparison (fraction of rec. amount)
124
Nutrient Density
* Amount of a given nutrient per (kilo)calorie
* Example #1:
– 1 cup of ice cream: 170 mg Ca++/265 kcal.
– 1 cup of nonfat milk: 300 mg Ca++/85 kcal
* Example #2: Next slide
125
Nutrient Density: the Potato
Oven-Baked Potato, with skin: 220 kcal +: – 0.07 mg Riboflavin, 3.33 mg Niacin
– 2.75 mg Iron
– 16 mg Sodium, 844 mg Potassium
* McDonald’s small french fries: 207 kcal +:
– 0 mg Riboflavin, 1.94 mg Niacin
– 0.53 mg Iron
– 135 mg Sodium, 469 mg Potassium
126
Dietary Guidelines
* See the Dietary Guidelines for Americans,
2020-2025 (links on Blackboard)
* Key recommendations (RPW, p. 41)
– Focus on healthy eating patterns
– Focus on variety, nutrient density, & amount
– Limit intake of added sugar, sat. fats, Na+
– Shift to healthier food, and beverage choices
– Support healthy eating patterns for everyone.
127
healthy eating plate
healthy oils
- use healthy oils (olive and canola oil) for cooking on salad, and at the table. Limit butter avoids trans fats
the more veggies - and the greater the variety - the better. Potatoes and french fries do not count lol
eat plenty of fruits of all colors
drink water, tea, or coffee. Limit milk/dairy
eat a variety of whole grains like oats, whole grain pasta, and brown rice. Limit refined grains like white rcs and white bread
choose fish, poultry, beans and nuts; limits red meat and cheese; avoid bacon, cold cuts and other processed meats
128
Estimated Calorie Requirements
* Amount depends on age and sex
* Sedentary
– Adults: 1600-2600 kcal
* Moderately Active
– Adults: 1800-2800 kcal
* Active
– Adults: 2000-3000 kcal
129
Estimated Energy Needs for Sedentary Adults
women
19-25 yr: 2000
26-50 yr: 1800
51+ yr: 1600
men
19-25 yr: 2600
26-40 yr: 2400
41-60 yr: 2200
61+ yr: 2000
130
Recommended Daily Intakes
for a person consuming 2,000 kcal/day
* Fruit Group: 2 cups (4 servings)
* Vegetable Group: 2.5 cups (5 servings)
– Dark green: 11⁄2 cups/week
– Red & orange: 51⁄2 cups/week
– Legumes (dry beans): 11⁄2 cups/week
– Starchy: 5 cups/week
– Other: 4 cups/week
131
Recommended Daily Intakes
for a person consuming 2,000 kcal/day
* Grain Group: 6 ounce-equivalents
– Whole grains: 3 oz.-equiv.
– Other grains: 3 oz.-equiv.
* Protein foods: 5.5 ounce-equivalents
* Dairy Group: 3 cups
* Oils: 6 tsp
132
What about the rest of us?
Appendix 3, Table A3-1 suggests amounts of food form the various groups for those who consume less or more than 2000 kcal/day. Excerpts on the following slide.
133
USDA Food Patterns: Fruits
Fruits contribute folate, vitamin A, vitamin C, potassium, and fiber.
Consume a variety of fruits, and choose whole or cut-up
fruits more often than fruit juice.
Apples, apricots, avocados, bananas, blueberries, cantaloupe, cherries, grapefruit, grapes, guava, honeydew, kiwi, mango, nectarines, oranges, papaya, peaches, pears, pineapples, plums, raspberries, strawberries, tangerines, watermelon; dried fruit (dates, figs, prunes, raisins); 100% fruit juices
Limit these fruits that contain solid fats and/or added
sugars:
Canned or frozen fruit in syrup; juices, punches, -ades, and fruit drinks with added sugars; tried plantains
1 c fruit =
1 c fresh, frozen, or canned fruit 1/2 c dried fruit
1 c 100% FruitUSDA Food Patterns: Vegetables Juice
134
USDA Food Patterns: Vegetables
Vegetables contribute folate, vitamin A. vitamin C, vitamin K. vitamin E. magnesium, potassium, and fiber.
Consume a variety of vegetables each day, and choose from all five subgroups several times a week.
Dark-green vegetables: Broccoli and leafy greens such as arugula, beet greens, bok choy, collard greens, kale, mustard greens, romaine lettuce, spinach, turnip greens. watercress
Red and orange vegetables: Carrots, carrot juice, pumpkin, red bell peppers, sweet potatoes, tomatoes, tomato juice, vegetable juice, winter squash (acorn, butternut)
Legumes: Black beans, black-eyed peas, garbanzo beans (chickpeas), kidney beans, lentils, navy beans, pinto beans, soybeans and soy products such as tofu, split peas, white beans
135
USDA Food Patterns: Vegetables (cont.)
Vegetables (continued from the previous slide
Starchy vegetables: Cassava, corn, green peas. hominy. lima
beans, potatoes
Other vegetables: Artichokes, asparagus, bamboo shoots, bean sprouts, beets, brussels sprouts, cabbages, cactus, cauliflower, celery, cucumbers, eggplant. green beans, green bell peppers, iceberg lettuce. mushrooms, okra, onions, seaweed, snow peas, zucchini
Limit these vegetables that contain solid fats and/or added sugars:
Baked beans, candied sweet potatoes. coleslaw. french fries, potato salad, and refried beans. scalloped potatoes. tempura vegetables
1 c vegetables =
1 c cut-up raw or cooked vegetables 1 c cooked legumes
1 c vegetable Juice
2 c raw, leafy greens
136
USDA Food Patterns: Grains
Grains contribute folate. niacin, riboflavin, thiamin, iron,
magnesium, selenium, and fiber.
Make most (at least half) of the grain selections whole grains.
Whole grains: amaranth, barley, brown rice, buckwheat, bulgur, cornmeal, millet. oats, quinoa. rye. wheat, wild rice and whole-grain products such as breads. cereals. crackers, and pastas; popcorn
Enriched refined products: bagels, breads. cereals, pasta (couscous, macaroni, spaghetti), pretzels, white rice, rolls, tortillas
Limit these grains that contain solid fats and/or added sugars:
Biscuits, cakes, cookies, cornbread, crackers, croissants, doughnuts, fried rice, granola, muffins, pastries, pies, presweetened cereals, taco shells
1 oz grains=
1 slice bread
1/2 c cooked rice, pasta, or cereal 1 oz dry pasta or rice
1 c ready-to-eat cereal
3 c popped popcorn
137
USDA Food Patterns: Protein Foods
Protein foods contribute protein, essential fatty acids, niacin, thiamin, vitamin B6, vitamin B12, iron, magnesium, potassium, and zinc.
Choose a variety of protein foods from the three subgroups, including seafood in place of meat or poultry twice a week.
Seafood: Fish (catfish, cod, flounder, haddock, halibut, herring, mackerel, pollock, salmon, sardines, sea bass, snapper, trout, tuna), shellfish (clams, crab, lobster, mussels, oysters, scallops, shrimp)
Meats, poultry, eggs: Lean or low-fat meats (fat-trimmed beef, game, ham, lamb, pork. veal), poultry (no skin), eggs
Nuts, seeds, soy products: Unsalted nuts (almonds, cashews, filberts, pecans, pistachios, walnuts), seeds (flaxseeds, pumpkin seeds, sesame seeds, sunflower seeds), legumes, soy products (textured vegetable protein, tofu, tempeh), peanut butter, peanuts
Limit these foods that contain solid fats and/or added sugars:
Bacon; baked beans; fried meat, seafood, poultry, eggs, or tofu; refried beans: ground beef; hot dogs; luncheon meats; marbled steaks; poultry with skin: sausages; spare ribs
1 oz protein foods=
1 oz cooked lean meat, poultry, or seafood 1 egg
1⁄4 c cooked legumes or tofu
1 tbs peanut butter
1⁄2 z nuts or seeds
138
USDA Food Patterns: Milk & Milk Prods.
Milk and milk products contribute protein, riboflavin, vitamin B12, calcium, potassium, and, when fortified, vitamin A and vitamin D.
Make fat-free or low-fat choices. Choose other calcium-rich foods if you don't consume milk.
Fat-free or 1% low-fat milk and fat-free or 1% low-fat milk products such as buttermilk, cheeses, cottage cheese, yogurt; fat- free fortified soy milk
Limit these milk products that contain solid fats and/or added sugars:
2% reduced-fat milk and whole milk; 2% reduced-fat and whole- milk products such as cheeses, cottage cheese, and yogurt; flavored milk with added sugars such as chocolate milk, custard, frozen yogurt, ice cream, milk shakes, pudding, sherbet; fortified soy milk
1 c milk or milk product =
1 c milk, yogurt, or fortified soy milk 1 1⁄2 oz natural cheese
2 oz processed cheese
139
USDA Food Patterns: Oils
ils are not a food group, but are featured here because they contribute vitamin E and essential fatty acids.
Use oils instead of solid fats, when possible.
Liquid vegetable oils such as canola, corn, flaxseed, nut, olive, peanut, safflower, sesame, soybean, sunflower oils; mayonnaise, oil-based salad dressing, soft trans-fat-free margarine; unsaturated oils that occur naturally in foods such as avocados, fatty fish, nuts, olives, seeds (flaxseeds, sesame seeds), shellfish
Limit these solid fats:
Butter, animal fats, stick margarine, shortening
1 tsp oil =
1 tsp vegetable oil
1 tsp soft margarine
1 tbs low-fat mayonnaise 2 tbs light salad dressing
140
Is your serving a “serving?”
* Most bagels today weigh 4+ ounces, equal to 4+ servings!
141
What you need to know (typical questions)
* On average, how many servings per day of fruit should a person who consumes 2000 kcal per day have?
* If Table A2-1 & A3-1 (DGA 2010, Table 2-3 and Appendix 7) information is given: On average, how many servings per day of whole grains should a Moderately Active 25-year-old woman have?
142
Grains: not all are the same
* As-is
* Refined
* Enriched or Fortified (+ Fe, thiamin, riboflavin, niacin, folate)
* Whole-grain
143
Daily Values (DV)
* Average recommended daily intake for a person on a 2000-kcal. diet (Note: average, not based on age or sex)
* See inside of the back cover of RPW for a list.
* The number on the label is the fraction (%) of the DV of a given nutrient in one serving.
* Utility of DV is to compare foods, not to accurately determine adequacy for a given individual.
144
Personal Daily Values
* Some DV’s can be ‘personalized:’
– Fat: 30% of kcal intake (9 kcal/g) [65g]
– Saturated fat: 10% of kcal intake (9 kcal/g) [20g]
– Carbohydrate: 60% of kcal intake (4 kcal/g) [300g]
– Fiber: 11.5g/1000 kcal intake [23g, or ~25g] (proposed change: 14g/kcal)
– Protein: 10% of kcal intake (4 kcal/g) [50g]
* Others (cholesterol [300 mg – same for all adults], vitamins, minerals)
145
Claims on food labels
nutrient
health
structure-function
146
Nutrient Claims
* Indicates the specific content of a nutrient.
* FDA defines and regulates (Link to claims allowed by FDA on Blackboard)
* E.g., cholesterol-free:
– <2 mg cholesterol/serving
– ≤ 2 g saturated fat/serving
* E.g., high fiber: 5 g or more per serving
* See RPW Glossary, p. 61
147
Health Claims
* Describes association between nutrient/food and a health problem.
* FDA approval is required (Link to claims allowed by FDA on Blackboard)
* Different from Structure-Function Claims, which do not require FDA approval
* “A list” example: Ca and reduced risk for osteoporosis: Ca ≥ 20% of DV; P ≤ Ca
* More examples: next 2 slides
148
More “A” health claims (examples)
* Folate and neural tube defects
* Low fat, low saturated fat and low cholesterol, and coronary heart disease
* Saturated fat, cholesterol, trans fat and heart disease
* Foods with soluble fiber and coronary heart disease
* Whole grain foods and risk of heart disease and certain cancers
149
More “A” health claims (examples)
* Low sodium & adequate potassium, and hypertension & stroke
* Non-sugar sweeteners and dental caries
* Fluoridated water and dental caries
* Low fat and cancer
* Fiber-containing foods and cancer
* Fruits and vegetables and cancer
150
Structure-Function Claims
* No FDA approval required
* Must not mention any disease or symptom
* Compare:
– H.C.: “May reduce the risk of heart disease.” – S.-F.C.: “Promotes a healthy heart.”
* Examples:
– “Builds strong bones.” “Improves memory” “Slows aging.” “Guards against colds,
151
What is the RDA for this nutrient (vitamin or mineral) and population?
#3 which is 62
#2 is the EAR
152
Which of the following has the highest Ca nutrient density? (data for 1 serving, showing % of DV of Ca [1000mg])
* Cereal #1: 1⁄2 cup, 100 kcal, 2% of DV (20 mg)
* Cereal #2: 1 cup, 100 kcal, 4% of DV (40 mg)
* Cereal #3: 1 cup, 200 kcal, 2% of DV (20 mg)
* Cereal #4: 1⁄2 cup, 300 kcal, 8% of DV (80 mg)
* Cereal #2: 1 cup, 100 kcal, 4% of DV (40 mg)
cereal #2: 40mg/100 kcal = 0.40 mg/kcal
or
cereal #2: 4% of DV/100 kcal = 0.040%/kcal
153
Which of the following has the highest Zinc nutrient density?
Shown: g/serving, % Zn DV, kcal/serving
1. W.C: 47g, 30%, 160 kcal
2. S.W.B: 55g, 15%, 200 kcal
3. O.C.C.: 25g, 25%, 100 kcal
4. T.O.S: 56g, 35%, 210 kcal
5. Ch.: 30g, 25%, 110 kcal
3. O.C.C.: 25g, 25%, 100 kcal
25% of DV/100 kcal = 0.250%/kcal
154
The folate RDA for a 19-30-y/o woman is 400 μg. and the UL is 1000 μg. This means that ...
1. The average 19-30- y/o woman needs 400 μg./day.
2. It is probably safe for a 19-30-y/o woman to consume 1000 μg./day.
3. Both of the above.
2. It is probably safe for a 19-30-y/o woman to consume 1000 μg./day.
155
On average, how many cups (servings) per day of vegetables should a person who consumes 2000 kcal per day have?
1. 0.5(1)
2. 1 (2)
3. 1.5(3)
4. 2 (4)
5. 2.5(5)
6. 3 (6)
5. 2.5(5)
156
Preview of next question
On average, how many oz.-eq. per day of whole grains should a moderately active 25-year-old woman have?
1. 2.0-2.5
2. 3.0-3.5
3. 4.0-4.5
4. 5
5. 6-7
6. 7-8
2. 3.0-3.5
157
Which of the following is not a
connection made by an FDA-allowed
Health Claim?
1. Cholesterol intake and hypertension
2. Fat intake and heart disease
3. Folate intake and neural tube defects
4. Sodium intake and hypertension
5. Non-sugar sweeteners and tooth decay
1. Cholesterol intake and hypertension
158
“A list” health claims (examples)
* Folate and neural tube defects
* Low fat, low saturated fat and low
cholesterol, and coronary heart disease
* Saturated fat, cholesterol, trans fat and heart disease
* Foods with soluble fiber and coronary heart disease
* Whole grain foods and risk of heart disease and certain cancers
159
More “A” health claims (examples)
* Low sodium & adequate potassium, and hypertension & stroke
* Non-sugar sweeteners and dental caries
160
“Personal” Daily Values
The following information will be supplied on exam #4, and you may need it this morning:
- fat: 30% of caloric intake
– Saturated fat: 10% of caloric intake – Carbohydrates: 60% of caloric intake – Protein: 10% of caloric intake
– Fiber: 11.5g/1000 kcal
161
For an adult consuming 2400 kcal/day, what is the personal D.V. of fat?
1. 65g
2. 80g
3. 100g
4. 300g
5. 720g
2. 80g
For an adult consuming 2400 kcal/day, what is the personal D.V. of fat?
* 30% x 2400 kcal = 720 kcal * 720 kcal / 9 kcal/g = 80 g
162
One serving of Girl Scout Thin Mints (4 cookies) contains 8g of fat. What fraction of this person’s personal D.V. is that?
1. 8%
2. 10%
3. 12%
2. 10%
Personal D.V. = 80 g
8 g / 80 g = 10%
163
Excessive consumption of EtOH leads to all of the following...
1. DecreaseinpH.
2. Decrease in [NADH].
3. Increased synthesis of fatty acids.
4. Increased formation of ketone bodies.
2. Decrease in [NADH].
164
Alcohol Metabolism: liver (cont.)
(1) EtOH + NAD+ → Acetaldehyde + NADH + H+
(2) Acetaldehyde + CoA + NAD+ → Acetyl CoA + NADH + H+ [Catalyzed by (1) alcohol dehydrogenase and (2) acetaldehyde dehydrogenase]
* Consequences of consuming alcohol over the liver’s ability to metabolize it:
– Decrease in pH (increase in H+)
– NADH inhibits CAC
– Acetaldehyde:
– Acetyl-CoA accumulates, and begins to be transformed into fatty acids (fatty liver, fibrosis,
cirrhosis) and ketone bodies (ketosis)
165
Which has the lower Km for EtOH, alcohol dehydrogenase, or the MEOS enzyme?
1. ADH
2. MEOSenzymes
1. ADH
166
MEOS
* Besides ADH, the liver has a microsomal ethanol-oxidizing system.
* Metabolizes alcohol and various drugs.
* ADH has Km=0.04 mM for EtOH. MEOS has Km=11 mM for EtOH.
167
At an EtOH concentration of 1.0 mM, which enzyme will be most actively metabolizing the EtOH?
1. Alcohol dehydrogenase
2. MEOS enzymes
1. Alcohol dehydrogenase
168
At an EtOH concentration of 15 mM, which enzyme(s) will be actively metabolizing the EtOH?
1. Alcohol dehydrogenase
2. MEOS enzymes
3. Both
4. Neither
3. Both
169
MEOS
In addition to ADH, the liver also has a microsomal ethanol-oxidizing system.
* Metabolizes alcohol and various drugs.
* ADH has Km=0.04 mM for EtOH. MEOS has Km=11 mM for EtOH.
* Repeated high blood [EtOH] stimulates the synthesis of MEOS enzymes.
* At high [EtOH], EtOH metabolized more than drugs, resulting in elevated [drug] – a potentially serious problem.
170
disulfiram inhibits ___
if a person who is taking this drug consumes alcohol, that person's blood serum level of ___ will increase, resulting in ___
1. alcohol dehydrogenase, ethanol, flushing (redness) of the face
2. alcohol dehydrogenase, ethanol, ketosis
3. acetaldehyde dehydrogenase, ethanol, formation of fatty acids in the liver
4. acetaldehyde dehydrogenase, acetaldehyde, flushing (redness) of the face
5. acetaldehyde dehydrogenase, acetaldehyde, ketosis
4. acetaldehyde dehydrogenase, acetaldehyde, flushing (redness) of the face
171
Acetaldehyde
Causes and consequences of acetaldehyde accumulation (highly reactive and toxic):
– Excess consumption of alcohol leads to increased acetaldehyde formation.
* Symptoms: alcohol flushing (redness), nausea, headache
– Disulfiram inhibits acetaldehyde dehydrogenase. * a drug sometimes used to treat alcoholism
172
Alcohol abuse commonly leads to a
_____ deficiency.
1. Niacin
2. Riboflavin
3. Thiamin
4. Vitamin E
5. Vitamin K
3. Thiamin
173
Alcohol Abuse and Metabolism
Most common vitamin deficiencies: folate, thiamine, B6, B12, D, A
174
Alcohol & Nutrition
1⁄2 oz. ethanol in:
– 5 oz. wine (100 kcal)
– 10 oz. wine cooler (135 kcal)
– 12 oz. beer (150 kcal; light: 80-130 kcal)
– 11⁄2 oz. distilled liquor (100-110 kcal)
Absorption through stomach walls – faster on an empty stomach
175
Alcohol Metabolism & Absorption
Alcohol dehydrogenase breaks down some alcohol in the stomach; men generally have more than women, leading to a higher tolerance.
* EtOH is absorbed by gastric mucosa, but even more rapidly by small intestinal mucosa (much greater surface area).
* Fat delays gastric emptying, and thereby slows EtOH absorption.
176
Alcohol Metabolism: liver
From the digestive tract, EtOH is transported to the liver for metabolism.
* The liver (alcohol dehydrogenase) can metabolize ~1/2 oz. alcohol per hour; if the input is greater, the excess is transported to other cells.
* During a fast, alcohol dehydrogenase may be broken down (to provide energy); this decreases the liver’s ability to metabolize alcohol.
177
Alcohol Metabolism: liver (cont.)
(1) EtOH + NAD+ → Acetaldehyde + NADH + H+
(2) Acetaldehyde + CoA + NAD+ → Acetyl CoA + NADH + H+ [Catalyzed by (1) alcohol dehydrogenase and (2) acetaldehyde dehydrogenase]
Consequences of consuming alcohol in excess of the liver’s ability to metabolize it:
– Decrease in pH (increase in H+)
– NADH inhibits CAC
– Acetaldehyde: see following slide
– Acetyl-CoA accumulates, and begins to be transformed into fatty acids (fatty liver, fibrosis,
cirrhosis) and ketone bodies (ketosis)
178
Acetaldehyde
Causes and consequences of acetaldehyde accumulation (highly reactive and toxic):
– Excess consumption of alcohol leads to increased acetaldehyde formation.
– Some populations have an inactive isoform of acetaldehyde dehydrogenase: unable to catabolize acetaldehyde, so it accumulates.
* Symptoms: alcohol flushing (redness), nausea, headache
* associated with lower incidence of alcoholism
– Disulfiram inhibits acetaldehyde dehydrogenase. * a drug sometimes used to treat alcoholism
179
MEOS
In addition to ADH, the liver also has a microsomal ethanol-oxidizing system.
* Metabolizes alcohol and various drugs.
* ADH has Km=0.04 mM for EtOH. MEOS has Km=11 mM for EtOH.
* Repeated high blood [EtOH] stimulates the synthesis of MEOS enzymes.
* At high [EtOH], EtOH metabolized more than drugs, resulting in elevated [drug] – a potentially serious problem.
180
MEOS (continued)
If a heavy drinker stops drinking, the elevated [MEOS enzymes] may metabolize drugs more rapidly.
* Such fluctuations may make it difficult to determine correct dosages.
181
Alcohol in the brain
Regions affected by elevated [EtOH]:
– Frontal lobe (judgment & reasoning)
– Midbrain (speech and vision)
– Cerebellum (vol. muscle control; may lead to staggering and slurred speech)
– Pons, medulla oblongata (respiration and heart action)
182
Alcohol and Weight
Moderately heavy drinkers (who have to metabolize the moderately high amount of alcohol they consume) have greater energy (calorie) intake and tend to gain weight (esp. “central obesity”).
* Very heavy drinkers generally eat poorly and often suffer from malnutrition (don’t consume enough nutrients and lose weight).
183
Alcohol Abuse and Metabolism
Folate deficiency
– Not retained by the liver
– Over-excreted by kidney
– Poorly retained and absorbed by the intestine
Thiamine deficiency
– Reduced intake and poor absorption
– Wernicke-Korsakoff syndrome (paralysis of eye muscles, poor muscle coordination, impaired memory)
184
Alcohol Abuse and Metabolism
Vitamin B6 deficiency
– De-protected, degraded by alcohol
– Impairs production of red blood cells
Vitamin B12 deficiency
– Poorly absorbed by the intestine
Vitamin D deficiency
– Insufficient activation by the liver
185
Alcohol Abuse and Metabolism
Vitamin A deficiency
– Retinol not converted to retinal in eyes
– Retinal not converted to retinoic acid in liver
Summary: folate, thiamine, B6, B12, D, A
186
