Exam 2 - Metabolism Flashcards
location of TCA
mitochondria
location of glycolysis
cytosol
ATP yield of one cycle of glycolysis
7 ATP (given NADH = 2.5 ATP)
regulation of glycolysis
product inhibition
allosteric control
covalent modulation
Fats can be converted to glucose. T/F?
F, it can only be converted as far as acetyl CoA due to irreversibility
Glycolysis and gluconeogenesis are both regulated at the same time. T/F?
F, both processes have different rate-limiting steps
Alanine is used as a substrate for glycolysis in the glucose-alanine cycle. T/F?
F, it is converted back to pyruvate for use in gluconeogenesis.
Glucose to pyruvate conversion requires a lot of energy. T/F?
T
hormone initiating glycolysis
insulin
hormone initiating gluconeogenesis
glucagon
Enzyme:
Fructose-6-P → Fructose-1,6-biP
PFK (phosphofructokinase)
Enzyme:
Fructose-1,6-bisphosphate → Fructose-6-Phosphate
fructose-1,6-biPase
Enzyme:
PEP → pyruvate
pyruvate kinase
absorption pathway of short- and medium-chain FAs
enter portal blood directly from enterocytes (readily absorbed)
bound to albumin
oxidized in the liver
absorption pathway of long-chain FAs
form chylomicrons and lipoproteins
drain into lymphatics via lacteals
enter bloodstream via thoracic duct into SCV
lipoproteins with the least and most proteins
most: HDL
least: chylomicron
lipoproteins with the least and most lipids
most: chylomicron
least: HDL
lipoproteins with the least and most fats
most: chylomicron
least: HDL
lipoproteins with the least and most free and esterified cholesterol
most: LDL
least: chylomicron
lipoproteins with the least and most phospholipids
most: HDL
least: chylomicron
LDL marker apoprotein
Apo B100
cofactor for LCAT
Apo A-I
cofactor for LPL
Apo C-II
enzyme inhibitors for LPL
Apo A-II and Apo C-III
ennzyme inhibitor for CETP
Apo C-I
ligands for LDL receptor
Apo B100 and Apo E
ligand for HDL receptor
Apo A-I
apoprotein with highest affinity to LDL receptor
Apo B100
enzyme catalyzing RLS in FA oxidation
acyl CoA synthetase
esterifies FA to CoA
net ATP produced from beta oxidation of 14-C saturated FA
formula: 14(n-1) + 10 - 2; where n = C/2
net ATP = 14(6) + 10 - 2 = 92 ATP
sources of acetyl CoA for FA synthesis
oxidative decarboxylation of pyruvate from glucose
oxidative degradation of some proteins
beta-oxidation of long-chain FA
sources of cholesterol
dietary - 0.4g/day
biliary/de novo - 2g/day
enzyme regulating cholesterol synthesis
HMG-CoA reductase
process involving HMG-CoA synthase and HMG-CoA lyase
ketogenesis
glucose hydrolysis intermediate converted to glycerol
DHAP
derivatives of cholesterol
corticosteroids
steroid hormones
bile salts and acids
Vit D
function of serum albumin
carrier protein for steroids, FAs, thyroid hormones
sources of N incorporated into urea during urea cycle
aspartate and ammonia
majority derived from glutamate
links urea cycle to TCA
fumarate
Why should essential AA be part of the diet?
The body cannot synthesize essential AA de novo and thus relies on external sources.
cofactor to forward homoCys –> Met
Vit B12
cofactor to forward homoCys –> Cys
Vit B6
possible condition following Vit B12 and B6 deficiency
homocystinuria
AA needing supplementation in diet of Px with phenylketonuria
tyrosine
impaired pathway in phenylketonuria
phenylalanine –> tyrosine
thus, tyrosine is deficient and needs supplementation in diet
principal action of thyroxine
increase O2 production increases metabolism (BMR)
factor directly related to BMR
lean body mass
importance of dietary proteins
provide essential amino acids for protein synthesis
suggested food to lower cholesterol
oat bran and other soluble fibers that reduce LDL levels
dietary fibers
decrease TAGs
increase stool bulk
improves chyme transmission
kwashiorkor
grossly underweight (<70% below normal) edema loss of pigmentation in hair and skin hypoalbuminemia moon facie and wet form
marasmus
extremely low weight
extreme wasting - loss of fat and muscle
dry form and geriatric face
cause of marasmus
calorie, protein, and nutrient deficiency
cause of kwashiorkor
protein deficiency despite adequate intake of calories
e.g. substituting milk for cassava
optimal proportion of carbs, fats, and proteins in diet
55~70% carbohydrates
20~30% fat
10~15% proteins
glycemic index
measure of blood glucose levels in response to food with respect to a standard food
glycemic load
glycemic index * carbohydrate concentration of food
food with relatively high glycemic index
bread > pasta and rice
biochemical measure of obesity/overnutrition
serum LDL
deficiencies resulting in anemia
folic acid
Vit B12
reaction associated with Vit C
hydroxylation - oxidizes the iron
oxidized Vit C is less/no longer effective
treatment for megaloblastic anemia from Vit B12 deficiency
folic acid
retinal
active form of Vit A
stored in liver
product of B-carotene hydrolysis
retinal
Vit D deficiency in children
rickets
Vit D deficiency in adults
osteomalacia
fat-soluble vitamins
Vit A, D, E, K
precursor of thiamine pyrophosphate
Vit B1
thiamine
Vit B1
riboflavin
Vit B2
Vit B6
pyridoxal, pyridoxine, pyridoxamine
thiamine deficiency
beri-beri
Wernicke-Korsakoff Syndrome
pellagra
can result from niacin deficiency
can lead to 3Ds - dermatitis, diarrhea, dementia
ascorbic acid
Vit A
precursor of lycopene and B-carotene
plant carotenoids
reason for regulation of metabolism
energy source does not have the same distribution as energy stores
importance of glucose phosphorylation to G6P
keep glucose inside cells
RLS in glycolysis
GLUT4 insulin dependence
insulin dependent
1, 2, 3, 5 are insulin INdependent
enzyme forming fructose-2,6-biP
Enzyme II
effect of phosphorylation of Enzyme II
decrease of fructose-2,6-biP concentration
energy change with PEP –> pyruvate
large negative delta-G
energy consumption of PEP –> pyruvate
2 ADP
location of PEP –> pyruvate
cytosol
Catabolic enzymes are usually active when phosphorylated. T/F?
T
…and anabolic enzymes are active when DEphosphorylated
catabolism
breakdown
oxidation
exergonic
[think: CAT bOx]
anabolism
synthesis
reduction
endergonic
ATP yield of NADH
2.5 ATP
ATP yield of FADH2
1.5 ATP
process not involving net influx of energy from other sources
catabolism
exergonic reaction: releases energy to other sources
step involved in substrate level phosphorylation in TCA cycle
succinyl CoA –> succinate
ATP produced in ETC by complete glucose oxidation
glycolysis: 2 NADH = 5 ATP
oxidative phosphorylation: 2 NADH = 5 ATP
TCA cycle: 2 FADH2 + 6 NADH = 3 + 15 ATP
total: 5 + 5 + 3 + 15 = 28 ATP
predominant glycerol derivative in intestinal lumen after Orlistat discontinuation
2-MAG
intermediates of odd-chain FAs entering TCA
succinyl CoA + acetyl CoA
What is acetyl CoA converted into for transport into cytoplasm from mitochondria (and v.v.)?
citrate
enzyme affected by enteropeptidase deficiency
pepsin
Maple Syrup Disease
accumulation of V, I, L
amplification
allows small amount of signal molecule to cause an increased intracellular transduction
effect of anaerobic glycolysis on GLUT4
increases activity
difference of hexokinase and glucokinase
glucokinase: in liver, phosphorylation only at high glucose levels, increased by insulin
hexokinase: in extrahepatic tissues, inhibited by G6P
location of pyruvate carboxylase
only in the mitochondria
compounds based on tyrosine
catecholamines (epinephrine, norepinephrine, dopamine) melanin thyroid hormones (T3, T4)
AA precursor of serotonin
tryptophan
factor increasing digestibility and absorption of dietary lipids
longer FA length
precursor FA for other FAs
palmitate
provides reducing equivalents in lipid synthesis
glucose
location of lipid synthesis
cytoplasm
characteristics of essential fatty acids
not naturally synthesized by humans
synthesized by plants (and some animals)
help maintain membranes
double bonds at delta-12 and delta-15 (o-6 and o-3)
location of double bonds in essential FAs
delta-12
delta-15
omega-3 precursor
linoleic acid
entry point of proprionyl CoA into TCA cycle
proprionyl CoA –> succinyl CoA
odd-numbered FAs enter glucogenic pathway via ___ (intermediate)
proprionyl CoA
Acetoacetic acid and B-hydroxybutyrate are weak acids. T/F?
F, they are rather strong.
location of ketogenesis
liver mitochondria
substrate used in ketogenesis
acetyl CoA
cofactor/s of lysly oxidase (collagen synthesis)
Vit C and iron
negative nitrogen balance
N intake < N loss
conditions presenting negative nitrogen balance
burns, fevers, wasting diseases, serious injuries
fasting, malnutrition
positive nitrogen balance
N intake > N loss
conditions presenting positive nitrogen balance
growth, tissue repair, pregnanacy
Athletes usually have lower BMRs (compared to non-athletes). T/F?
F, they have slightly higher BMRs.
TCA cycle is purely anabolic. T/F?
F, it has both anabolic and catabolic phases.
final common pathway for metabolism of glucose, FAs, and AAs
TCA cycle
The TCA cycle produces oxidizing equivalents for the ETC. T/F?
F, it produces reducing equivalents.
Carbohydrate energy stores are bulky and not readily available. T/F?
F, they are bulky but they are more readily available.
Fat stores are bulky and not readily available. T/F?
F, they are not readily available but compact.
Amino acids are glucose sources but have other uses. T/F?
T
source of blood glucose replenishment
breakdown of dietary CHO
methotrexate
anticancer drug
primary folate antagonist
methorexate mechanism
inhibits reduction of dihydrofolate to tetrahydrofolate (THF, which helps in nucleotide formation)
First Law of Thermodynamics
Energy is neither created nor destroyed but converted into other forms.
free energy value in spontaneous metabolic reaction
negative free energy value (dG)
nervous excitation is (endergonic / exergonic)
endergonic
active transport is (endergonic / exergonic)
endergonic
muscular contraction is (endergonic / exergonic)
endergonic
fuel oxidation is (endergonic / exergonic)
exergonic
amphibolic pathway
TCA cycle
products of acetyl CoA oxidation in TCA
NADH, FADH2, CO2
ATP yield from isocitrate –> fumarate
isocitrate -> a-ketoglutarate + NADH = 2.5 ATP
a-ketoglutarate -> succinyl CoA + NADH = 2.5 ATP
succinyl CoA -> succinate + GTP = 1 ATP
succinate -> fumarate + FADH2 = 1.5 ATP
total = 2.5 + 2.5 + 1 + 1.5 = 7.5 ATP
(some) pathways producing reducing e- for ETC
TCA cycle
B-oxidation
aerobic glycolysis
used to form H2O at the end of ETC
O2
location of ETC
inner membrane of mitochondria
Phosphorylation reactions synthesize ATP. T/F?
T
Why does muscle contraction increase the rate of oxidative phosphorylation?
ADP concentration is increased.
mechanism of hydrogen sulfide
inhibits cytochrome oxidases (in complex IV)
leads to loss of consciousness and cardiopulmonary arrest
result of oxidative phosphorylation uncoupling by dinitrophenol
ATP production stops
oxygen uptake continues
ADP
product of ATP hydrolysis
positive effector for glycolysis and TCA cycle
signals low enery level in the cell
final electron acceptor in the ETC
O2
direct energy source for ATP synthase to produce ATP
proton gradient established in mitochondria
changes in metabolism in the heart following MI
decreased rate of oxidative phosphorylation
increased rate of lactic acid synthesis
increased use of glucose by muscle tissue
cellular compartment becoming acidic (filled with H+) during mitochondrial electron transport
space between inner and outer mitochondrial membrane
As affinity of the enzyme for substrate decreases, Km also decreases. T/F?
F, substrate affinity and Km are inversely proportional.
Km
substrate concentration at 1/2 Vm
expressed in units of concentration
organic precursors of coenzymes
vitamins
Noncompetitive inhibition is irreversible. T/F?
F, both competitive and noncompetitive inhibition are reversible.
reverses competitive inhibition
addition of excess substrate
Reversible inhibition entails covalent bond formation. T/F?
F, reversible inhibition involves noncovalent interactions (H-bonds, hydrophobic interactions, ionic bonds) while irreversible inhibition usually involves covalent bonds.
electron acceptor of cyt c oxidase
O2
protein directly catalyzing fibrin hydrolysis
plasmin
isozymes
enzymes with different AA sequences catalyzing same chemical reaction
(e.g. hexokinase and glucokinase)
competitive inhibition
increases Km
inhibitor is usually a structural analog of substrate
via noncovalent interactions
function of pyridoxal phosphate as cofactor
amino group carrier
organ with highest demand for glucose as fuel
brain
Why isn’t skeletal muscle glycogen involved in blood glucose regulation?
Only the liver has G-6-Pase which allows glucose release into the blood.
counter-regulatory hormones to insulin
glucagon
epinephrine
cortisol
Not all enzymes involved in gluconeogenesis are in the cytosol. T/F?
T, some are in the sER and mitochondria.
processes regulating glycolysis
covalent modification (pyruvate kinase inhibited by high [ATP]) allosteric control (PFK) hormonal regulation (role of glucagon)
products of anaerobic glycolysis of 1 glucose
2 ATP + 2 lactate
possible Px presentation of insulinoma (insulin-secreting tumor)
obesity
hypoglycemia
products of transamination of aspartate and a-ketoglutarate
OAA + glutamate
AA utilized to transport ammonia to the liver
A and Q
diet causing high [urea] in urine
very low CHO, very high CHON
ketogenic AA
yields acetoacetyl CoA through ketogenesis
exclusively ketogenic: L, K
keto- and glucogenic: W, I, F, T, Y
glucogenic AA
yields glucose through gluconeogenesis
~all AA except K and L
Why is arginine semi-essential?
synthesizable via urea cycle
required intake dependent on health status and stage of development
compounds involved in metabolism of 1-C compounds
THF
SAM
B12 (methylcobalamin)
AA donating amino groups for purine synthesis
G, Q, D
activated sugar utilized for both purine and pyrimidine de novo synthesis
PRPP
deficient enzyme in hyperuricemia
hypoxanthine-guanine phosphoribosyl transferase (HGPT)
disorders associated with hyperuricemia
Lesch-Nyhan syndrome
gout
mechanism of allopurinol
inhibits xanthine oxidase (xanthine –> uric acid)
decreases uric acid formation
inhibits purine synthesis
indication/s for allopurinol
hyperuricemia
gout
mechanism of methotrexate
inhibits DHFR (DHF --> THF) inhibits synthesis of DNA, RNA, thymidylates, proteins
indications of methotrexate
cancer
autoimmune diseases
mechanism of 5-fluoroacil
inhibits thymidylate synthase (dUMP –> TMP)
inhibits RNA synthesis
indications for 5-fluoroacil
cancer