Bio Chem (Metabolism) Flashcards
Glycolysis Tissue
all tissues
Glycolysis Cellular compartment
cytosol
Glycolysis substrate
glucose
Glycolysis key enzymatic step
PFK-1* (rate limiting)
Hexokinase (found everywhere)
Glucokinase (pancreas and liver)
Glycolysis product
pyruvate
Glycolysis regulators
(+) insulin, Fructose 2,6-bisphosphate, AMP
(-) too much ATP or citrate
(-) ATP
Glycolysis Cofactors
Mg
Glycolysis Key intermediates
Glucose-6-phosphate can’t leave the cell once converted
Glycolysis energy production
2 pyruvate
2 ATP
2 NADH
Pyruvate oxidation tissue
tissue that have mitochondria and oxygen
Pyruvate oxidation location
mitochondrial matrix
Pyruvate oxidation substrate
pyruvate
Pyruvate oxidation Cofactors and key enzyme
Pyruvate dehydrogenase needs
thiamine, niacin, riboflavin,
NAD, FAD, TPP, CoA, lipoic acid
Pyruvate oxidation product
acetyl CoA
Pyruvate oxidation regulation
(+) NAD, ADP
Pyruvate oxidation energy production
2 acetyl CoA
2 NADH
2 NADH
Anaerobic glycolysis tissue
tissue w/o oxygen
Anaerobic glycolysis cellular compartment
cytosol
Anaerobic glycolysis substrate
pyruvate
Anaerobic glycolysis key enzyme step/cofactor
lactate dehydrogenase
NAD, FAD, TTP
Anaerobic glycolysis product
lactate can be toxic if can’t eliminate
Anaerobic glycolysis regulators
(+) NADH
Anaerobic glycolysis energy generation
-NADH
Krebs cycle tissue
all tissues, but liver is most significant
Krebs cycle cellular compartment
mitochondrial matrix
Krebs cycle substrate
acetyl CoA
Krebs cycle key enzyme/cofactor
isocitrate dehydrogenase (1st energy generating step) and alpha ketoglutarate dehydrogenase
AKDH needs same 5 cofactors as pyruvate dehydrogenase - NAD, FAD, TPP, CoA, lipoic acid
Krebs cycle product
Co2, NADH, FADH2, GTP
Krebs cycle regulation
(+) NAD, FAD, GDP
(-) ATP, citrate
Krebs cycle energy productions
(+) 3 NADH
(+) 1 FADH
(+) 1 GTP
(run through twice for one molecule of glucose)
(+) FADH
Glycogen synthesis tissue
liver
Glycogen synthesis cellular compartment
cytosol
Glycogen synthesis substrate
glucose
Glycogen synthesis key enzyme step
phosphoglucomutase (commits glucose to pathway)
glycogen synthase (links glucose molecules)
Glycogen synthesis product
glycogen
Glycogen synthesis regulation
(+) UTP
Glycogen synthesis key intermediates
UDP-glucose
Glycogen synthesis energy production
-1 ATP/glucose
Glycogenolysis tissues
liver, muscle
Pentose Phosphate Pathway/HMP Shunt tissues
liver, RBC mammary gland, adrenal cortex
Pentose Phosphate Pathway/HMP Shunt cellular component
cytosol
Pentose Phosphate Pathway/HMP Shunt substrate
glucose-6P
Pentose Phosphate Pathway/HMP Shunt key enzyme step
glucose-6P dehydrogenase (oxidative)
transktetolase (non-oxidative, requires TTP)
Pentose Phosphate Pathway/HMP Shunt product
NADPH, ribose sugars
Pentose Phosphate Pathway/HMP Shunt key intermediates
NADPH
Fatty Acid Synthesis tissues
liver, adipose, mammary glands, kidney
Fatty Acid Synthesis cellular component
cytosol (leaves mitochondria via citrate shuttle)
Fatty Acid Synthesis substrate
acetyl coA
Fatty Acid Synthesis key enzyme step
acetyl coA carboxylase (requires biotin)
fatty acid synthase (has B5 as part of structure)
Fatty Acid Synthesis product
palmitate
Fatty Acid Synthesis regulation
(+) insulin
Fatty Acid Synthesis key intermediates
malonyl coA
Fatty Acid Synthesis energy production
-1 ATP/malonyl CoA, -2 NADPH/malonyl CoA
Beta oxidation tissues
liver, muscle, kidney
Beta oxidation cellular component
mitochondria (peroxisome)
Beta oxidation substrate
fatty acyls
Beta oxidation key enzyme step
acetyl CoA synthase
Beta oxidation product
acetyl coA, NADH, FADH2
Beta oxidation regulation
(+) glucagon
Beta oxidation key intermediates
fatty acyl coA, fatty acyl carnitine
Beta oxidation energy production
16C saturated FA = 129 ATP (131 total - 2 ATP for activation)
ketogenesis tissue
liver
ketogenesis cellular component
mitochondrial matrix
ketogenesis substrate
acetyl coA
ketogenesis key enzyme step
HMG CoA synthase
ketogenesis product
beta-hydrozybuterate dehydrogenase, acetone, acetoacetate
ketogenesis regulation
(+) acetyl CoA
ketogenesis key intermediates
HMG CoA
ketogenesis energy production
-2 acetyl coA, -1 NADH
ketone degradation tissues
brain, skeletal muscle, heart muscle
NOT liver
ketone degradation cellular component
mitochondrial matrix
ketone degradation substrate
products of ketogenesis
beta-hydrozybuterate dehydrogenase, acetone, acetoacetate
ketone degradation key enzyme step
beta-hydrozybuterate dehydrogenase
ketone degradation product
acetyl coA
ketone degradation key intermediates
HMG CoA
ketone degradation energy production
+2 acetyl coA, +1 NADH, -1 GTP
cholesterol synthesis tissue
liver
cholesterol synthesis cellular component
cytosol
cholesterol synthesis substrate
acetyl coA
cholesterol synthesis key enzyme step
HMG CoA reductase
cholesterol synthesis product
cholesterol
cholesterol synthesis regulation
(+) insulin
cholesterol synthesis key intermediates
HMG CoA, mevolonate –> CoQ
cholesterol synthesis energy production
lots
body doesnt usually break it down for energy
urea cycle tissue
liver
urea cycle cellular component
cytosol, mithochondrial matrix
urea cycle substrate
NH4+, glucose, CO2, aspartate
urea cycle key enzyme step
CPS I (Rate limiting)
urea cycle product
urea
urea cycle regulation
(+) N-acetyl glutamate
urea cycle key intermediates
arginine, fumarate
urea cycle energy production
-2 ATP
gluconeogenesis tissues
liver, kidney, SI
gluconeogenesis cellular component
mitochondrial matrix, cytosol, ER
gluconeogenesis substrate
alanine (AA), lactate (AR), glycerol (Lipids)
gluconeogenesis key enzyme step
pyruvate carboxylase/ PEP carboxykinase
PFK I
G6P
gluconeogenesis product
glucose
gluconeogenesis regulation
(+) acetyl coA
(-) F26-bisP
(-) F26-bisP
gluconeogenesis key intermediates
pyruvate, fructose-1,6-bisP, glocuose 6P
gluconeogenesis energy production
- 2 pyruvate
- 2 NADH
- 4 ATP
- 2 GTP
glycogenolysis tissues
liver, muscle
glycogenolysis cellular component
cytosol
glycogenolysis substrate
glycogen
glycogenolysis key enzyme step
glycogen phosphorylase
requires biotin) (glucose 6P
glycogenolysis product
G6P or glucose (liver only)
glycogenolysis regulation
(+) AMP, cAMP
(-) glucose
glycogenolysis key intermediates
G6P
what are the monosaccharides
glucose
fructose
galactose
mannose
what are the disaccharides
sucrose
lactose
maltose
isomaltose
what bond is on maltose
a1-4
what bond is on lactose
b1-4
lactase specific
what bond is on sucrose
a1-b2
what types of bonds are on glycogen
a1-4 (base chains)
a1-6 (branch points)
what types of bonds are on cellulose
b1-4 (making it indigestible)
what is unique about the beta bond in lactose?
humans usually cant break down/digest beta bonds; but with lactose there is a specific lactase enzyme that allows us to
amylose vs amylopectin structure
amylose is unbranched, helix
amylopectin branched chains of glucose
what are the polysaccharides
glycogen
inulin
cellulose
polysaccharides in carb absorption are broken down to monosaccharides by what
brush border enzymes
carb absorption; fructose is brought in via..
facilitated diffusion
what biochemical rxns take place in the mitochondria?
krebs cycle fatty acid oxidation formation of acetyl coA part of urea cycle part of gluconeogenesis
what biochemical rxns take place in the golgi?
synthesis and packaging of complex molecules including glycolipis, glycoproteins, and lipoproteins
what biochemical rxns take place in the cytosol
glycolysis HMP shunt protein synthesis fatty acid synthesis part of urea cycle part of gluconeogenesis
what biochemical rxns take place in the lysosomes
degradation of complex macromolecules
what biochemical rxns take place in the nucleus
DNA and RNA synthesis
most ATP is formed in which cellular component?
mitochondria
why break down proteins, carbs, and fats into acetyl-coA (C2) in the TCA/krebs/citric acid acycle?
to link them with oxaloacetate (C4) and create citric acid/citrate
vitamins with role in TCA
thiamin (B1)
riboflavin (B2)
niacin (B3)
pantothenic acid (B5)
how is H oxidation accomplished in ox-phos?
by splitting hydrogen atom into H+ ion and free electron
pathologies associated with ox phos of electron transport chain
uncoupling
inhibition = blocking respiratory chain at places other that ADP+P posiotion
poisons, insecticids, antibiotics, barbituates
where does the electron transport chain take place?
INNER membrane of mitochondria
glycolysis aerobic/anaerobic
can occur under both
aerobic glycolysis ends at pyruvate
anaeorbic ends at lactate (less energy produced)
hexokinase is found mainly in what tissue
muscle cells
glucokinase is found mainly in what tissue
liver cells
what is the major controller of liver glycogen metabolism
concentration of phosphorylase-a
increased cAMP has what effect on
glycogenesis
glycogenolysis
SLOWS glycogenesis (inactivation of glycogen synthase)
MORE glycogenolysis (activation of phosphorylase)
HMP shunt primary functions
alternative route for glucose metbolism
- generates NADPH
- provides ribose residues
HMP shunt ATP generation
NONE
what are eicosanoids
biologically active 20 carbon fatty acids that give rise to cytokines/prostanoids (prostaglandins, thromboxanes, leukotrienes)
of the 3 series of eicosanoids, which are completely essential and which are conditionally essential?
linoleic (omega 6) and alpha linoleic (omega 3) fatty acids are completely essential
arachodonate is conditionally essential
role of eicosanoids
gives rise to individual sets of prosaglandin, leukotriene, and thromboxane (PG-1, LK-1, TX-1, PG-2, LK-2, etc..) to work in concert to create inflammatory and anti-inflammatory balance
what are the three series of eicosanoids
series 1: linoleic acid (omega 6)
series 2: arachadonic acid
series 3: alpha-linolenic acid (omega 3)
which series of eicosanoid is pro-inflammatory
series 2: arachadonic acid
what enzyme breaks down arachadonate out of membrane phospholipid > arachadonic acid
PLA-2 (phospholipase A2)
what enzyme converts arachadonic acid > leukotrienes
lipoxygenase
what enzyme converts arachadonic acid > prostaglandins/thromboxanes
cyclooxygenase
what are the essential amino acids
Three Liars, Val, Lucy, and Me, Tripped and Fell in His Isolation Tank
threonine lysine valine leucine methionine tryptophan arginine phenylalanine histidine isoleucine
non-essential amino acids
Almost All Girls Go Crazy After Getting Taken Prom Shopping
alanine aspartate glutamate glycine cysteine asparginine glutamine tyrosine proline serine
what makes up the tripeptide glutathione and which is the rate limiting AA for formation
glutamic acid/glutamine
cysteine (RL)
glycine
what is a zymogen
give an example
inactive precursor of an active enzyme
Ex:
zymogen: trypsinogen
enzyme: trypsin
how do enzymes speed up thermodynamically favorable reactions
lower energy of activation by binding to a SUBSTRATE
an enzyme is NOT part of any product
enzyme activity (reaction rate) is affected by:
temp
pH
what are co-factors
small molecular weight substances (B vitamins and trace minerals) that are neede to help some enzymes react
typically the cofactor is part of the substrate binding site, on the enzyme
enzymes; difference between competitive vs non-competitive inhibition
competitive: binds at substrate binding site
non-competitive: binds to non-substrate site
products of HMP shunt are important in which processes
nucleic acid synthesis
steroid synthesis
hepatic phase I detox
which part of the urea cycle occurs in the mitochondria?
NH4+CO2 > carbamoyl phosphatase (CP)
CP > L-citrulline
which part of the urea cycle occurs in the cytosol?
series of transaminations resulting in L-arginine going to urea + L-ornithine
L amino acids are actively transferred across the intestines with the help of what?
vitamin B6
what cofactor is necessary for alanine aminotransferase rxns?
vit B6 derivative
for the following AA name the alpha-keto acid and enzyme for its conversion
alanine
glutamate
aspartate
alanine > (ALT) > pyruvate
glutamate > alpha ketoglutarate
aspartate > (AST) > oxaloacetate
What is the enzyme produced by the brush border and pancreas, and is responsible for the cleaving of single amino acids off of the carboxy end of the peptides?
Carboxypeptidase
Which enzyme is responsible for converting IMP and GMP into their nucleoside forms?
5’-nucleotidase
what is choleterol an important precursor for?
bile acids
steroid hormones
vitamin D
what metabolic process is Carnitine Acyl transferase involved in
lipolysis
what metabolic process is Acetyl CoA carboxylase involved in
lipid synthesis
what metabolic process is HMG CoA reductase involved in
cholesterol synthesis
what metabolic process is HMG CoA synthase involved in
ketogenesis
What is the rate-limiting enzyme involved in steroid synthesis
20,22-desmolase
what does the enzyme hydrolase do
adds H2O to break bonds (hydrolysis)
what does the enzyme aldolase do
cleaves C-C bonds to form aldehydes
what does the enzyme dehydrogenase do
removes H from substrate
what does the enzyme hydratase do
adds H2O to C-C bonds without breaking bond
can also remove H2O to create double bond
what does the enzyme isomerase do
converts between isomers
cis/trans, D/L, aldolase/ketolase
what does the enzyme esterase do
hydrolyzes ester linkages to form an alcohol and acid
first step of liver detox pathway
phase 1 - hydroxylating cytochrome 450 system; makes fat soluble compounds water soluble
CYP450
(-OH added)
second step of liver detox pathway
phase 2 - enzymatic conjugation
takes water soluble/polar intermediates and adds an “anchor” by conjugating them with amino acids
last step of liver detox pathway
excretion
bile
serum > urine
regulatory enzyme for lipolysis
carnitine acyltransferase
regulatory enzyme for fat mobilization
hormone sensitive lipase
regulatory enzyme for lipid synthesis
acetyl-CoA carboxylase
regulatory enzyme for cholesterol synthesis
HMG CoA reductase
regulatory enzyme for pentose phosphate shunt
G6P dehydrogenase
regulatory enzyme for ketone body synthesis
HMG CoA synthase
regulatory enzyme for purine synthesis
amidotransferase
preferred nutrient of brain for
normal:
prolonged fast:
normal: glucose
fast: ketone bodies, glucose
preferred nutrient of muscle for
normal:
prolonged fast:
normal:
rest - fatty acids
exercise - glucose
fast: fatty acids
preferred nutrient of heart for
normal:
prolonged fast:
“takes anything”
fatty acids, ketone bodies, lactate, glucose for normal and fast
preferred nutrient of erythrocytes for
normal:
prolonged fast:
glucose for both normal and fasting
what do kinases do?
phosphorylate - take a phosphate group from high energy substrate (ATP) > ADP
adding a phosphate group (kinase is included in word, “hexokinase”) uses ATP, removing one (kinase separate from name “pyruvate kinase”) gains ATP
what is the purpose of glycolysis?
converting sugar to energy
what are the processes involving in aerobic respiration?
glycolysis
pyruvate dehydrogenase
TCA cycle
ETC
glycogenolysis
glycogenesis
gluconeogenesis
what are the fates of pyruvate?
pyruvate >
> actetyl CoA (pyruvate oxidation) ** most energy generating path
lactate (anaerobic glycolysis/lactic acid cycle)
alanine
oxaloacetate
what five cofactors are required for the pyruvate dehydrogenase enzyme complex involved in conversion of pyruvate to Acetyl CoA to prep for entry to TCA cycle?
thiamine pyrophosphate (B1)
lipoic acid
CoA (B5; pantothenic acid)
FAD (B2, riboflavin)
NAD+ (B3, niacin)
“The Lovely Co-enzymes For Nerds”
what is the purpose of anaerobic glycolysis? when would this occur?
to regenerate NAD+
cells without mitochondria (RBCs) or anaerobic conditions of skeletal mm
which complex of the ETC involves NADH? which involves FADH?
complex 1 - NADH
complex 2 - FADH2
what cofactor is involved with complex 3 of the ETC?
CoQ10
how many ATP is 1 NADH?
NPLEX RULES
3
how many ATP is 1 FADH?
NPLEX RULES
2
1 molecule of glucose =
NPLEX RULES
glycolysis: 2 NADH, 2 ATP
pyruvate: 2 NADH
TCA: 6 NADH, 2 GTP, 2 FADH
= 38 ATP (36-38 based on shuttles)
what are the intermediates of the krebs cycle?
Citrate
Is (isocitrate)
Krebs (aKG)
Starting (succinyl coA)
Substrate (succinate)
For (fumarate)
Making (malate)
Oxaloacetate
what are the shuttles that take biproducts into mitochodria?
malate shuttle (kidney, liver, heart)
gkycerol-3-phosphate shuttle (brain, skeletal muscle)
what does the malate shuttle do?
when there is high NADH:NAD in cytosol > moves NADH WITH concentration gradient
what does the glycerol 3 phosphate shuttle do?
when there is low NADH:NAD in cytosol > moves NADH AGAINST concentration gradient
(requires energy; -1 NADH, +1 FADH2; net loss of 1 ATP per pyruvate molecule»_space;> hence why 2 less ATP)
what bonds can amylase break?
alpha 1-4 (CAN’T break down alpha 1-6 in complex carbs)
what is gluconeogenesis?
production of glucose from NEW (non-carb) sources:
pyruvate, AAs, fats, glycerol, lactic acid
where in the body does gluconeogenesis occur?
liver
kidney (PCT)
small amounts in intestines
what transporter brings glucose into the liver? what about kidneys?
GLUT-2 (liver)
GLUT-3 (kidney)
key cofactor for hexokinase/glucokinase in glycolysis
magnesium
cofactors for LDH in anaerobic glycolysis
TPP (b1)
NAD (b3, niacin)
FAD (b2, riobflavin)
cofactors for isocitrate DH / aKG DH in TCA
same as PDH (TPP, NAD, FAD, Lipoic acid, CoA)
main purpose of PPP/HMP Shunt
produce NADPH
what main processes could Acetyl coA do?
- go into krebs cycle and make energy
- go into fatty acid synthesis
- go into cholesterol cynthesis
what molecules serve as “shunts” and move processes in and out of structures
fatty acyl carnitine
citrate
steroisomers
- enantiomers: mirror image (D vs L)
- diasteromers: non, mirror image
- epimer: differ at one carbon
- anomers: cyclized structures only, A or B
what are the monosaccharides
glucose
mannose
galactose
fructose
what are the digestible disaccharides
- sucrose (glucose-fructose)
- lactose (glucose-galactose)
- maltose (glucose-glucose)
GLUT 1
erythrocyte
blood — barrier
- brain
- retinal
- placental
- testis
GLUT 2
liver
kidney
pancreatic beta cells
serosal surface of intestinal mucosa cells
GLUT 3
brain (neurons)
GLUT 4
adipose tissue
skeletal muscle
heart muscle
insulin sensitive
GLUT 5
intestinal epithelium
spermatozoa
actually a fructose transporter
when do we want glycogen metabolism to occur? where?
when we want to store glucose or use reserves
cytosol
rate limiting step for glycogenolysis and its cofactor
glycogen phosphorylase
pyridoxal-5-phosphate (B6)
rate limiting step for glycogenesis
glycogen synthase
upregulation for glucose (gluconeogenesis OR glycogenolysis)
glucagon (liver only)
epinephrine
GTP
upregulation for glycogen
insulin; will encourage glucose uptake into cells and glycogen formation
rate limiting step of glycolysis and what upregulates it?
phosphofructokinase
- amp
- h+
- fruc 2,6 biphos (inc with insulin)
fates of pyruvate
- pyruvate ox (mitochondrial matrix)
- anaerobic glycolysis (cytosol)
purpose of anerobic glycolysis
regenerate NAD+
cystol
cells without mitochondria (RBCs)
anaerobic conditions (skeletal muscle)
sources of acetyl coA for TCA cycle
- fatty acid (palmitate) beta ox
- ketone body (acetoacetate) metabolism
- glucose
- pyruvate oxidation
- amino acid (alanine) catabolism
- ethanol metabolism
ketogenic vs glucogenic AA function
ketogenic AA can be ox to form acetyl coA for ketone body genesis during ketosis
purely keto: lysine and leucine
both: PITTT, phenylalanine, isoleucine, tyrosine, tryptophan, threonine
all others glucogenic (converted > glucose during gluconeogenesis)
TCA rate limiting step
isocitrate dehydrogenase
ETC location
inner mitochondrial membrane
ETC complexes and inhibiting factors
- complex I: - by rotenone
- complex II (succinate dehydrogenase)
- complex III: - by antimycin A
- complex IV: - by cyanide, CO
- complex V: - by oligomycin
insulin secretion
secretion is
- stim by glucose
- inhibited by epi
insulin function relationship to metabolism
causes glucose uptake, synthesis of
- glycogen
- protein
- fat
what enzyme is involved in insulin receptor activation
receptor tyrosine kinase >phosphorylates insulin receptor and IRS
insulin v glucagon cells
insulin beta cells
glucagon alpha cells
glucagon secretion
stim by low glucose or inc epi
inh by insulin
what enzyme is involves in glucagon activation
adenylate cyclase > protein kinase
fructose metabolism
- mostly liver (sometimes small int or kidney)
- enters cells via facilitated diffusion
- insulin independent
- rate limiting step: aldolase B
def of aldolase B vs def of fructokinase
def aldolase B:fructose intolerance
def fructokinase: fructosuria