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Week 2 Foundations - Sheet1 Flashcards

1
Q

Glycolysis: Phase I requires an investment of _______

A

2 ATP and Glucose,

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2
Q

Glycolysis: Phase II or the generating phase provides _____

A

2 ATP (net; 4 for this phase) and 2 NADH and 2 pyruvate

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3
Q

aldolase

A

glycolysis–cleaves glucose into two molec

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4
Q

hexokinase

A

catylizes the first rxn of glycolysis in most tissue. The rxn requires an invenstment of ATP –> ADP. Regulation primarily by substrate and product.

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5
Q

glucokinase

A

catylizes the first rxn of glycolysis in LIVER. This rxn requires an investment of ATP–>ADP. Note that this enzyme has a larger Km. Regulation primarily by substrate and product.

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6
Q

glucose 6-phosphate

A

result of the rxn from glucose using hexokinase/glucokinase. This second molec in glycolysis can be used in gluconeogenesis, glycogenolosis, and pentose phosphate pathway.

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7
Q

Phosphoglucose isomerase (a.k.a. phosphoglucomutase)

A

reversably converts glucose 6-phosphate fructose 6-phosphate

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8
Q

phosphofructokinase-1

A

fructose 6-phosphate fructose 1,6-bisphosphate. This rxn requires ATP–>ADP and is the last investment. Allosteric regulation by (+) AMP and fructose 2,6-bisphosphate (produced by PFK-2); (-) ATP and citrate

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9
Q

Fructose 2,6-bisphosphate

A

produced by PFK-2 in the reaction Fructose 6-phosphate Fructose 2,6-bisphosphate; this serves as an inhibitor of PFK-1. This reaction is not a part of glycolosis and serves as a secondary messenger

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10
Q

If there is a high [fructose 6-phosphate], what will happen? Think glycolysis…

A

PFK-2 will convert to fructose 2,6-bisphosphate, which allosterically activates PFK-1 and converts fructose 6-phosphate to fructose 1,6-bisphosphate–thus increasing glycolysis. PFK-2 is activiated by glucagon and AMP

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11
Q

pyruvate kinase (PK)

A

converts phosphenolpyruvate —> pyruvate (provides ADP–>ATP). Regulated by substrate and product in ADULT tissue.

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12
Q

fight or flight response

A

epinephrine–>heterotrimeric G protein coupled receptor–>cAMP, PKA—> glycogenolosis—>glucose into circulation

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13
Q

glycogenolosis

A

(glycogen–>glucose 1-phosphate—-> glucose 6-phosphate) hepatocyte)—-> glucose

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14
Q

Important relationship between ATP and PFK-1

A

ATP is substrate and regulator of PFK-1. There are to binding sites: 1 for use in kinase activity and 2 allosteric inhibition site. At higher concentrations ATP is an allosteric inhibitor.

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15
Q

PFK-1 has an overall significance in glycolysis…

A

rate limitiing step

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16
Q

PK-M2 splice varient

A

Normally expressed only in embryonic tissue, but can be expresed in cancer. This is thought to contribute to cancer cells’ altered metabolism

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17
Q

Cancer cells have an increased rate of glucose uptake. How does PK-M2 help a cancer cell?

A

PK-M2 is a low activity isoform of pyruvate kinase. This slows down glycolysis flux and increases the diversion of substrates from glycolysis.

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18
Q

2,3-bisphosphoglycerate

A

binds at a site distant from the oxygen-binding site and regulates the O2-binding affinity of hemoglobin. 2,3-BPG stabilizes deoxyhemoglobin; thus increaseing O2 delivery to tissue. Draw out mechanism and enzymes

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19
Q

Pathology: PDH deficiency
poison, e.g. cyanide
ischemia (lack of O2)
ethanol

Implications for glycolysis?

A

If there is a problem downstream of pyruvate, the cell must get all its ATP through glycolysis, with lactic acid as the product. This will decrase blood pH

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20
Q

Ischemia

A

is a loss of blood perfusion and oxygen delivery to tissue. If a cell doesn’t have oxygen. . .

The NADH/NAD+ ratio increases
Product inhibition of the pyruvate dehydrogenase reaction
Substrates for lactate dehydrogenase (pyruvate and NADH) favors lactate production

The AMP / ATP ratio increases
AMP acts as an allosteric activator of PFK-1
AMP activates AMP-K, which activates PFK-2, making more F-2,6-bP, activating PFK-1
The rate of glycolysis is increased

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21
Q

HIF pathway and ischemia

A

ischemia means tissue hypoxia–> HIF pathway activated. Hypoxia-inducible factor (HIF) regulates gene expression such that glycolysis increases. One way is through activation of PDH kinase, which phosphorylates and shuts down PDH –> so [pyruvate] increases and Lactate DH activity increases.

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22
Q

two essential amino acids in diet

A

linoleic (18:2), linolenic (18:3)

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23
Q

hormone sensitive lipase reacts with what three hormones?

A

stored fat mobilization occurs due to glucagon, epinephrine, norepinephrine

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24
Q

How does palimtoyl-CoA cross the impermeable inner mitochondrial matrix?

A

It takes the carnitine shuttle.

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25
Enoyl-CoA hydratase can only accept what kind of double bond?
can *only accept trans-double bonds*, but most unsaturated FA in diet have trans!? So **enoyl CoA isomerase converts cis to trans in previos step
26
What happens when the liver’s store of glycogen is depleted?
3-hydroxybutyrate, acetoacetate
27
The ______ is the site of ketone body synthesis
Liver
28
Ketone bodies produced in the liver can be used as fuel by
brain, heart, and skeletal muscle
29
The absence of elevated ketone bodies in a hypoglycemic patient suggests a defect in ____________________, such as ________________.
fatty acid metabolism; medium chain acyl-CoA dehydrogenase deficiency (MCAD).
30
activation of fatty acids is required for beta-oxidation. This requires...
binding to acyl-CoA. This involves Fatty Acyl Co-A synthetase and requires ATP---> AMP. So ATP + FA ----> Fatty Acyl CoA + AMP + 2Pi
31
Reye Syndrome
Multisystem organ failure, particularly affecting the brain and liver, caused by mitochondrial dysfunction
32
What are the two routes to gain NADPH?
malic enzyme (malate---> pyruvate) and the pentose phosphate pathway
33
malate dehydrogenase
enzyme of the CAC. Converts Malate---->OAA (NAD+ ---> NADH)
34
citrate lyase
cytosolic: converts citrate (from mito; CAC) to acetyl CoA and OAA. **Acetyl CoA can then enter FA synthesis
35
In conditions of excess energy, ___________________ is inhibited by a high NADH/NAD+ ratio. This drives citrate towards fatty acid synthesis.
The CAC is inhibited and specifically inhibits **isocitrate dehydrogenase, which is responsible for increasing [citrate] --> leaves mito, is converted by citrate lyase to acetyl CoA (FA synthesis) and OAA (which can reenter mito).
36
In lipid synthesis, _____ is produced to continue glycolysis
NAD+
37
NADPH is involved in what kind of pathways
biosynthetic pathways
38
pentose phosphate pathway (main point)
biosynthetic purposes and production of NADPH
39
The pyruvate / malate cycle has two functions in lipogenesis
1) Transports acetyl CoA from the mitochondria to the cytosol. 2) Malic enzyme generates NADPH to power fatty acid synthesis.
40
ACC
acetyl CoA carboxylase-first step of fatty acid synthesis. (Biotin!) Regulation: (+) Citrate allosterically activates (feed forward), Insulin increases transcription, Xylulose 5-phosphate increases transcription, Insulin stimulates dephosphorylation, activating the enzyme; (-) Palmitoyl CoA allosterically inhibits (product inhibition), Phosphorylation by AMP-PK inhibits, Glucagon --> cAMP --> PKA --> inhibitory phosphorylation
41
feed forward allosteric regulation
[substrate] of enzyme regulates
42
__________inhibits carnitine palmitoyl transferase I, preventing β-oxidation of newly synthesized fatty acids.
Malonyl CoA
43
AMPK or AMP-PK
AMP activated protein kinase. Responds to an increase in [AMP] (which means low ATP) and by phophorelating key enzymes to increase energy levels (and shut off FA synthesis and other biosynthetic paths.)
44
In β-oxidation of fatty acids, the reaction sequence is:
(occurs in mito) oxidation, hydration, oxidation, bond cleavage
45
In fatty acid synthesis, the reaction sequence is:
(occurs in cytoplasm) bond formation (decarboxylation), reduction, dehydration, reduction--one enzyme does all this!
46
Fatty acid synthase
Primary enzyme responsible for FA synthesis. Has two important active sites with sulfur groups--substrate flips back and forth adding carbon. Produces palmitate
47
Cofactor for FA synthase?
acetyl CoA?
48
FA synthesis: Elongation
Palmitoyl CoA can be elongated, two carbons at a time, in the endoplasmic reticulum. Malonyl CoA donates the two carbons, and the added keto group undergoes the same reduction, dehydration, and reduction to produce a saturated fatty acyl chain. Palmitate is produced and is saturated!
49
FA synthesis: Unsaturation
The body can unsaturate carbon carbon bonds if they are at least nine carbons away from the ω end.
50
ω-3 and ω-6 fatty acids are obtained from plant and fish oils, and are essential dietary precursors for synthesizing ________.
eicosonoids--paracrine hormones (substances that act only on cells near the point of hormone synthesis). ***Aracadonic acid is the precursor to eicosonoids. Nonsteroidal antiinflammatory drugs such as aspirin and ibuprofen block aracadonate from conversoin to eicosonoids
51
__________ and ________are the two most important dietary unsaturated fatty acids
Linoleic (18:2(9),1(2) and linolenic (18:3(9),(12),(15), (((arachidonic (10:4) also))))
52
Arachidonic acid
is a precursor of prostaglandins. It can not be synthesized de novo, because it has carbon – carbon double bonds near the ω carbon. Linolenic acid consumed in the diet can be converted to arachidonic acid by elongation and introducing two carbon – carbon double bonds.
53
FA synthesis occurs in the _____
Liver
54
Triacylglycerol is made up of
three fatty acyl chains linked to a glycerol backbone. Glycerol 3-phosphate is the source of the glycerol backbone.
55
The two enzymes that make glycerol 3-phosphate
glycerol kinase (FROM LIPOLYSIS in liver) (glycerol----> glycerol 3-phosphate (Requires ATP--> ADP)), glycerol 3-phosphate dehydrogenase (FROM GLYCOLYSIS in liver and adipocytes) (dihydroxyacetone phosphate ---> glyceral 3-phosphate (NADH--> NAD+))
56
lipoprotein lipase (LPL)
LPL cleaves off fatty acids, which then enter cells. They undergo β-oxidation for energy in muscle cells, and they are stored as triacylglycerols in adipocytes.
57
storage of lipids requires what active process in adeipocytes?
glycolysis to produce glycerol 3-phosphate via glycerol 3-phosphate dehydrogenase
59
phospholipids
use glycerol as a backbone. Have two FAs and Head Group
60
___________are mainly used in cell membranes, but also are constituents of lipoproteins, bile, and lung surfactant.
Glycerophospholipids
61
The inner mitochondrial membrane is rich in ....
cardiolipin
62
cardiolipin
is a component of the inner mitochondrial membrane. It is formed by linking phosphatidyl glycerol (a glycerophosphate with a glycerol head group) with CDP diacylglycerol. Is more ridged and larger than most membrane lipids---> impermiability
63
Sphingolipids
use ceramide instead of glycerol for their backbones. Ceramide is derived from serine and palmitoyl CoA.
64
The most important sphingolipid is ______________, which is present in the myelin sheaths of nerve fibers. The head group is choline.
sphingophospholipid sphingomyelin
65
Surfactants are required in the lungs to prevent ______
alveolar collapse
66
The ratio of what two lipids in amniotic fluid is a useful indicator of gestational progress
sphingomyelin to phosphatidylcholine
67
leptin
released from adipocytes-->acts on hypothalmus--->satiety (behavior)
68
Leptin and STAT
JAK receptors bind leptin, JAK phosphorylates STAT---> which acts as transcription factor for anorexigenic factors that depress appetite
69
malonyl CoA decarboxylase
Involved in FA synthesis. Opposite of ACC. Converts malonyl CoA into acetyl CoA (and loses CO2)
70
cell structure: Phospholipids
establish basic membrane structure. Can be glycosylated
71
cell structure: Cholesterol
stiffens membranes
72
cell structure: Glycolipids
have sugar component (minor population in membrane). Can be neutral or negatively charged. Glycolipids carry out functions in cell recognition and adhesion, and charged glycoproteins can influence the electrical properties of membranes. Enriched in neurons and apical surfaces of epithelial cells.
73
cell structure: Phosphatidylinositols
involved in cell signaling (minor population in membrane). Kinases can phosphorelate different portions of the inositol portion
74
amphipathic molecules
possess hydrophobic and hydrophilic regions
75
inositol 1,4,5 trisphosphate (IP3)
binds to smooth endoplasmic reticulum and opens calcium ion channels to release Ca++ into the cytoplasm, which is then able to bind and modulate the functions of many calcium-binding proteins
76
DAG
diacylglycerol-- serves as docking site for protein kinase C.
77
phosphoglyceride synthesis
in ER
78
sphingomyelin synthesis
made from sphingosine in the Golgi
79
Glycolipid synthesis
made from sphingosine in the Golgi
80
flipases
recognizes specific phospholipids and flip them between leaflets
81
There is a net ____ charge on the cytosolic side of the plasma membrane
negative, due to serine and amine functionalities. If there is a negative charge on outside--> signals poor cell health
82
lipid rafts
-Special membrane domains composed of specific types of lipids and proteins •Rich in sphingolipids, cholesterol, and certain proteins •May be sorted to transport vesicles and involved with ***signal transduction** events and other specialized functions.
83
Glycocalyx
function as barrier of *protection*. Have covelently attahced sugar groups.
84
Three ways proteins can be organized in membranes.
A: self-assembly into aggregates; B: tethered to extracellular molecules; C: tethered to intracellular molecules; D: bound to proteins on adjacent cells. Also, cell junctions (specifically, tight junctions) can establish apical and baso-lateral domains in membranes of epithelial cells.
85
The integral membrane protein integrin
binds to extracellular molecules such as collagen and fibronectin, as well as to intracellular elements such as the cytoskeleton. Binding to the extracellular matrix can organize integrins into patches, and affect their function as environmental sensors.
86
Cadherin
is a large integral membrane protein that self-associates in the presence of calcium ions. It is an important adhesive molecule, linking cells together that express the same type of cadherin
87
Functions of the ER:
§ Synthesizes protein (RER). SER; § Synthesizes lipid (RER and SER). § Metabolizes and detoxifies harmful compounds (SER). § Helps regulate Ca++ levels in the cell (RER and SER).
88
RER produces
All integral membrane proteins (including ER, Golgi, lysosomes, endosomes, secretory vesicles, and plasma membrane), except those of mitochondria and peroxisomes. § Luminal and secreted proteins.
89
what determines whether a polyribosome becomes attached to an ER membrane or remains free-floating in the cytoplasm?
Contained within produced polypeptide itself: ER signal sequence
90
prostagladins
any of various oxygenated unsaturated cyclic fatty acids of animals that are formed as cyclooxygenase metabolites especially from unsaturated fatty acids (as arachidonic acid) composed of a chain of 20 carbon atoms and that perform a variety of hormonelike actions (as in controlling blood pressure or smooth muscle contraction)
91
pyruvate carboxylase
pyruvate ---> Oxaloacetate. Requires **Biotin!!!
92
Single electron (e-) transfers to oxygen generate three reactive oxygen species (ROS)
superoxide, hydrogen peroxide, and hydroxyl radical
93
NADH dehydrogenase (Complex I)
Requires FMN and Fe-S. 4 H+ per NADH. Feeds into CoQ
94
succinate dehydrogenase (Comlex II)
Part of CAC. Converts succinate to fumarate. Reduces FAD to FAD2H. Feeds e- to CoQ. Not a transmembrane enzyme; pumps NO H+
95
cytochrome b-c1 complex (Complex III)
Pumps 4 H+ for each CoQH2(red). Feeds e- to cytochrome C. Has *heme group
96
cytochrome c oxidase (Complex IV)
Has *heme, *copper, *zinc, which pass electrons to O2. Pumps 2H+ for eacy Cytochrome C(red)
97
Cytochrome c
has *heme group
98
UCP1
uncoupling protein 1 (aka thermogenin). Dissapates H+ gradient accross inner mito membrane. This allows fat to be utilized for heat independently of ATP consumption
99
The effects of PDH deficiency are primarily neurological, affecting brain development. Why?
Brain can not utilize fatty acids, and needs glucose for fuel.
100
Hereditary or acquired PDH deficiency can result in lactic acidosis (a.k.a. lacticacidemia). Why?
pyruvate cannot get converted to acetyl CoA, so pyruvate is converted to lactate + **H+

Foundations (5 decks)

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