Review and Integration of Energy Metabolism (Exam II) Flashcards
Function of liver (metabolism)
- maintains blood glucose level (70-100mg/dL). It has glucose-6-phosphatase so its stored glycogen can contribute to blood glucose. It also makes glucose via glucogneogenesis
- preferentially uses fatty acids and amino acids for its own energy requirements, sparing glucose for glucose-dependent tissues.
- makes ketone bodies, an alternate fuel, BUT does not use them for its own energy requirements. Why? Lacks transferase that moves CoA from succinyl CoA to acetoacetate.
- deaminates amino acids (1° straight chain) and converts the toxic NH3 to non-toxic urea. The C-skeletons can enter the pathways of energy metabolism.
- makes fatty acids using acetyl CoA generated from pyruvate and NADPH from PPP; makes TAG by esterifying fa to glycerol; makes glycerol backbone from glucose.
Function of muscle (metabolism)
- stores glycogen for its own use during exercise
- under anaerobic conditions generates lactate which can be used by liver for gluconeogenesis (Cori Cycle)
- synthesizes and “stores” protein; no dedicated storage form for energy production
- resting muscle preferentially uses faty acids (takes them up from VLDLs in circulation) and amino acids, especially BCAA, (and ketone bodies, if available) for its energy needs
Function of adipose (metabolism)
Stores TAG. It takes up fa from VLDLs in the circulation and esterifies them to make TAG or oxidizes them to acetyl CoA; makes the glycerol 3-P from DHAP.
It degrades TAG to fa + glycerol BUT can’t use the free glycerol to make glucose because it lacks glycerol kinase. The glycerol is sent out and used by the liver (and kidney) to make glucose, as they do have glycerol kinase.
Cytosolic Reactions
- Glycolysis
- Glycogenesis
- Glycogenolysis
- FA synthesis
- PPP (Pentose Phosphate Pathway)
- Urea cycle (partly here, partly in mitochondria)
- Gluconeogenesis (partly here, partly in mitochondria)
Mitochondrial Reactions
- Matrix
a. PDH
b. TCA cycle (except succinate dehydrogenase: associated with mitochondrial
membrane)
c. β oxidation of fa (and ketogenesis in liver) - Inner membrane
a. oxidative phosphorylation
Hepatic Enzymes more active when I/G ratio is HIGH
acetyl CoA carboxylase (acetyl-CoA to produce malonyl-CoA)
fatty acid synthase (synthesis of palmitate from malonyl-CoA & acetyl CoA)
glucose 6-P dehydrogenase (PPP)
glycerol 3-P acyltransferase
glucokinase (glucose to G6P)
PFK1 (F6P to F-1,6-BP)
PK (PEP to pyruvate)
Hepatic Enzymes more active when I/G ratio is LOW
carnitine acyltransferase I (beta oxidation)
glucose 6-phosphatase (gluconeogenesis & glycogenolysis)
phosphoenolpyruvate carboxykinase (gluconeogenesis)
pyruvate carboxylase (pyruvate to OAA)
High energy signals
ATP
citrate
acetyl CoA (in cytosol)
Low energy signals
cAMP
AMP
ADP
P
High glucose signals
fructose-2,6-bisphosphate (in liver)
glucose-6-phosphate
Low glucose signals
cAMP
Acetyl CoA carboxylase: covalent effectors
active when deP; inactive when P
glycogen phosphorylase: covalent effectors
active when deP; active when P
glycogen phosphorylase kinase: covalent effectors
active when P; inactive when deP
glycogen synthase: covalent effectors
active when deP; inactive when P
PDH: covalent effectors
active when deP; inactive when P
PFK2 (kinase domain): covalent effectors
active when deP; inactive when P
PK: covalent effectors
active when deP; inactive when P
Absorptive State
high blood glucose levels; increased I/G ratio
store aa as protein, fat as TAG, glucose as glycogen
synthetic pathways are activated; degradative ones are inhibited
↑I, ↓G, ↓ cAMP, therefore ↓ cAMP-mediated phosphorylation of proteins and activation of phosphatases
Characteristics of blood in the absorptive state.
- Glucose levels will be high, perhaps as high as 8 mM.
- Insulin/glucagon ratio will therefore be high.
- Predominant circulatory lipids are lipoproteins, in particular, chylomicrons.
- Amino acids are present from the digestion of dietary proteins.
Muscle in absorptive state:
Increased
a. glucose uptake; uptake via GLUT4 is I-dependent. Glucose used for glycogen synthesis + for glycolysis
b. uptake and catabolism of BCAA; 1° site of BCAA transaminase
c. protein synthesis
Adipose in absorptive state:
- increased
a. glucose uptake; uptake via GLUT4 is I-dependent
b. glycolysis
c. activity of PPP due to increased glucose-6-phosphate; therefore, increased NADPH
d. NADPH allows for increased fa synthesis. Liver, however, remains primary site of fa synthesis.
e. TAG synthesis - decreased TAG degradation; ↑ I/G; ↓ HSL (de P)
Increased reactions of liver in absorptive state
Uptake of glucose and phosphorylation of glucose. Uptake via GLUT2 is insulin-independent, driven by glucose concentration. Phosphorylation to glc 6-P. Glucokinase is isozyme in liver: high Km, no direct product inhibition. Recall that frc and gal need own kinases.
Synthesis of glycogen via activation (deP) of glycogen synthase and increased availability of glc-6-P, its allosteric activator.
Activity of PPP because of increased glucose-6-phosphate and the use of NADPH in fatty acid synthesis that keeps G6PD active.
Glycolysis because of increased activity (and amount) of key glycolytic enzymes, e.g. activation of PFK1 by fructose 2,6-bisphosphate; pyruvate enters mitochondria, and is oxidized to acetyl CoA by PDH. PDH is active (deP) because its kinase is inhibited by pyruvate.
Fatty acid synthesis via activation of acetyl CoA carboxylase by deP and by increased availability of its ⊕ allosteric effector, citrate; increased availability of NADPH
from the PPP and malic enzyme. Use of NADPH raises NADP+/NADPH and keeps the pentose phosphate pathway active.
TAG synthesis due to increased glycerol from DHAP from glycolysis, and to increased fa. TAG out as VLDL.
Protein synthesis
Degradation of amino acids from food because more aa are present than the liver can use in biosynthesis; their α-ketoacids can be used in synthesis of fatty acids.
Decreased reactions of liver in absorptive state
Free fatty acid availability due to I-mediated decrease in HSL activity (de P) in adipose.
Fatty acid degradation due to increased malonyl CoA and its inhibition of CAT I.
Gluconeogenesis due to inactivation of pyruvate carboxylase because of the low levels of acetyl CoA, its ⊕ allosteric effector. The acetyl CoA is being used in
fa synthesis. Frc 2, 6-bis P from PFK-2 inhibits frc 1,6 bisphosphatase.
Glycogenolysis due to inactivation (deP) of phosphorylase kinase and phosphorylase.
Absorptive reactions: Glycogenesis (cytoplasm of liver muscle)
Glycogen synthesis (↑ I/G) involves the conversion of glc 6-P to glc 1-P which reacts with UTP to form UDP-glc. Glucose is transferred from UDP-glc to either the nonreducing end of glycogen via an α 1,4 link by glycogen synthase or to the protein, glycogenin, by autoglucosylation and the glucosyl chain extended via α 1,4 links by glycogen synthase. Glycogen synthase is regulated. It is covalently activated (deP) by ↑I/G and allosterically activated by glc 6-P. Insulin also increases glc uptake by muscle (GLUT 4), favoring glycogenesis.
Branches are added to the growing chain at ~ every 8 residues by branching enzyme (glucose 4,6 transferase), which transfer 5-8 glc residues from a non-reducing end to an internal residue via an α 1,6 link.
Absorptive reactions: Glycolysis (cytoplasm)
Oxidation of glucose to pyruvate; fructose-6-P to fructose-1,6-bisphosphate, the rate-limiting, committed step is catalyzed by PFK I, one of three irreversible reactions in glycolysis.
Net generation by substrate-level phosphorylation of 2 ATP/glucose; provides 2 NADH
NADH is oxidized back to NAD+1 by ETC under aerobic conditions (requires substrate shuttles), and by LDH under anaerobic conditions.
a. malate/asp shuttle
b. glycerol 3-P (α-glycerol phosphate) shuttle
Pyruvate becomes acetyl CoA under aerobic conditions; pyruvate becomes lactate under anaerobic conditions in muscle (also in RBC since no mitochondria), LDH requires NADH as a cosubstrate.
Glycolysis is inhibited by high ATP, BUT inhibition is overcome in liver by fructose-2,6-bisphosphate, synthesized by the bifunctional PFK2 when glucose level is high. Fructose-2,6-bisphosphate keeps glycolysis going so that fa can be synthesized and stored when glucose is abundant.
Frc and gal, products of carbohydrate digestion, enter glycolysis; each requires own kinase in liver. Hereditary fructose intolerance (deficiency of aldolase B) and classic
galactosemia (deficiency of galactose 1-phosphate uridylyltransferase) are important pathologies.
Absorptive reactions: Pyruvate dehydrogenase (PDH, PDHC)
The irreversible oxidation of pyruvate to the acetyl CoA occurs in the mitochondrial matrix by the multienzyme complex, pyruvate dehydrogenase, an α-keto acid dehydrogenase that is regulated covalently (inactive if P) by its own kinase and phosphatase. The kinase and phosphatase themselves are allosterically regulated.
E1 (decarboxylase) requires TPP, E2 (transacetylase) lipoate, and E3 (dehydrogenase) FAD as
coenzyme-prosthetic groups. α-KGD and BCKAD are other examples of α-keto acid dehydrogenases; common E3 with PDH.
Absorptive reactions: TCA, Krebs, Citric Acid Cycle (mitochondrial matrix)
Oxidizes acetyl CoA, produced by the breakdown of glucose, fa, and some amino acids to 2CO2.
Produces 1 GTP by substrate-level phosphorylation, produces reducing equivalents (3NADH, 1FADH2), regenerates oxaloacetate
Described as amphibolic: catabolism of molecules such as amino acids produces the 5C and 4C intermediates of the cycle while, in some tissues, cycle intermediates are used in anabolic processes.
Controlled by energy state of the cell: if ATP is low, cycle goes faster; if high, cycle slows and acetyl CoA builds up and is exported to cytoplasm as citrate for fa synthesis in liver and adipose. Also controlled by [NADH]. Important control point is isocitrate dehydrogenase: Ө ATP, NADH; ⊕ ADP, Ca+2. Citrate synthase (Ө citrate) and α- ketoglutarate dehydrogenase (Ө NADH, succinyl CoA; ⊕ Ca+2) are additional sites of regulation.
Absorptive recations: FA Synthesis (cytoplasm) (1° liver but also adipose)
From acetyl CoA when I/G ratio is high. Requires transport from mitochondria to cytoplasm of the acetyl part of acetyl CoA as citrate formed by condensation of acetyl CoA and OAA; citrate lyase regenerates acetyl CoA in cytosol.
Acetyl CoA is carboxylated to malonyl CoA by biotin-dependent acetyl CoA carboxylase. This ATP-requiring, rate-limiting and regulated step is increased by citrate
(allosteric) and deP (covalent) of the enzyme, and is decreased by P (AMPK) and palmitoyl CoA.
The malonyl CoA is acted upon by FA synthase, a dimeric enzyme with 7 catalytic activities that builds up a fa 2C’s at a time at COOH end until C16:0 (palmitic acid) is
produced. Process requires NADPH from PPP and malic enzyme.
7 cycles of condensation/decarboxylation, reduction, dehydration, reduction followed by one thiolytic cleavage
Generation of malonyl CoA is rate-limiting since malonyl is required in each condensation reaction.
Elongation and desaturation occur primarily in SER
a. Elongated at COOH end by addition of two C’s from malonyl Co A.
b. Humans lack ability to make n-6 or n-3 unsaturated fa such as linoleic and linolenic because we can’t desaturate between C10 and the ω-C.
Fatty acids (as TAG) are sent out of the liver in the very low density lipoprotein particles (VLDL). VLDL are a source of fatty acids for muscle and adipose. In muscle, the fatty acids are used for energy. In adipose, they can be used for energy or re-esterified to a glycerol backbone and stored as TAG.
Absorptive Reactions: Pentose Phosphate Pathway (PPP) or Hexose Monophosphate Shunt (HMP) (cytoplasm of liver, adipose, RBC)
Provides a major portion of the cell’s NADPH, plus some ribose-phosphate required for nucleotide synthesis
Produces 2 NADPH, 1 ribose 5-P and 1 CO2 per 1 glc 6-P
Important in liver and adipose for fatty acid synthesis
Linked to glycolysis because of the common intermediate glc-6-p
Regulated at glucose-6-P dehydrogenase by the NADPH/NADP+1: as ↑, pathway ↓
Important in RBC for the maintenance of glutathione (GSH); deficiency in glucose-6-P dehydrogenase in RBC leads to hemolytic anemia under oxidative stress. Why? Decrease in reduced (functional) glutathione. Heterozygote advantage with malaria
Post-absorptive (fasted) state
low blood glucose levels - low I/G ratio.
retrieve fats and CHO
synthetic pathways are inhibited; degradative pathways are activated
↓I, ↑G, ↑ cAMP, ↑ cAMP-mediated phosphorylation of proteins
Characteristics of blood in the fasted state
Glucose levels are maintained at about 4 mM.
Insulin/glucagon ratio is low.
Predominant circulatory lipids are free fatty acids bound to albumin.
Predominant circulating amino acids are glutamine and alanine.
Ketone bodies are present at increasing levels depending on the length of fasting.
Primary role of liver in post-absorptive (fasted) state:
increased glycogenolysis due to activation (P) of glycogen phosphorylase by its phosphorylated (activated) kinase
increased gluconeogenesis using glycerol from lipolysis of adipose TAG, lactate from anaerobic glycolysis, and glucogenic aa (primarily ala from BCAA catabolism in muscle); increased synthesis of PEPCK.
dephosphorylation of glc-6-P from glycogenolysis and gluconeogenesis to free glucose by glc 6-Pase (in ER); glc leaves liver and enters blood stream; results in ↓ glycolysis, ↓ PPP, ↓ glycogen synthesis
ketogenesis from acetyl CoA of β-oxidation spares glc; KB used by muscle, adipose, gut, brain but not liver (no transferase) or RBC (no mitochondria).
Increased reactions of liver in post-absorptive (fasted) state
TAG degradation in adipose due to activation (via phosphorylation) of HSL by PKA generates fatty acids and glycerol.
In liver, fatty acid oxidation generates acetyl CoA; also generates NADH and ATP needed for gluconeogenesis; glycerol is a substrate for gluconeogenesis. NADH inhibits TCA at ICD, so acetyl CoA is available for
ketogenesis. Increased availability of NADH also shifts OAA → malate and contributes to the rise in acetyl CoA. Increased acetyl CoA shunts pyruvate to gluconeogenesis: positive effector of PC and inhibitor of PDH.
Ketogenesis from acetyl CoA; regenerates the CoA needed for fatty acid oxidation
Decreased reactions of liver in post-absorptive (fasted) state
Glycogenesis due to decreased glc 6-P, and inactivation of synthase (↓ glc 6-P, ↑ phosphorylation)
Glycolysis due to decreased synthesis and activity of key glycolytic enzymes; decrease in frc 2,6-bisphosphate since P inhibits the kinase activity of PFK2.
Fatty acid synthesis due to decreased malonyl CoA; the decrease in malonyl CoA removes the inhibition
Adipose in post-absorptive (fasted) state:
Decreased uptake of glucose; shift to other fuels; increased degradation of TAG (HSL is phosphorylated and active) with increased release of ffa into the blood, and increased supply of glycerol to the liver for gluconeogenesis
Muscle in post-absorptive (fasted) state:
Decreased uptake of glucose; switches to fatty acid and KBs.
Fasted state: Glycogenolysis
Degradation (↓ I/G) involves sequential removal of glucose as glc-1-P via glycogen phosphorylase (P) until 4 glycosyl units remain before a branch, a limit dextrin. The
debranching enzyme clips off the outer 3 units and transfers them to non-reducing end of another chain (4:4 transferase). A second enzymatic activity (α-1:6 glucosidase) of this enzyme clips off the single remaining residue as free (non-phosphorylated) glucose.
With increased glucagon (liver) and epinephrine (liver + muscle), see cAMP-mediated activation of protein kinase A. Protein kinase A phosphorylates:
a. glycogen phosphorylase kinase (now active; it phosphorylates and activates
glycogen phosphorylase)
b. glycogen synthase (now inactive)
c. protein phosphatase inhibitor (now active)
Allosteric activation of phosphorylase kinase b by Ca+2 and of phosphorylase b by AMP.
Deficiencies in glycogen metabolism (1° catabolism) are known (glycogenoses).
a. glc 6-Ptase deficiency in Von Gierke or Type Ia GSD
Fasted State: Gluconeogenesis (mitochondria and cytoplasm of liver cells primarily; kidney in long-term
fasting/starvation)
Synthesis of glucose from pyruvate generated from lactate and amino acids (1° ala)
Requires pyruvate to be carboxylated to OAA by pyruvate carboxylase (allosteric activator is acetyl CoA). The OAA is reduced to malate which exits the mitochondria and is re-oxidized to OAA in the cytoplasm. The OAA is decarboxylated and phosphorylated
to PEP by PEPCK, regulated by enzyme induction in response to a decreased I/G ratio.
Dephosphorylation of fructose-1,6-bisP by fructose bisphosphatase is favored due to decreased availability of fructose-2,6-bisP.
Dephosphorylation of glc-6-P by glc-6-phosphatase in liver; ER enzyme that is deficient in Type Ia glycogen storage disease or Von Gierke disease.
Requires 4 ATP, 2 GTP, and 2 NADH per glucose made; ATP and NADH come from fa degradation, as does the positive effector of PC (acetyl CoA). Stimulated by cortisol. While fatty acid oxidation supplies the ATP and NADH needed for gluconeogenesis, there is no net synthesis of glucose from the acetyl CoA generated by fatty acid oxidation (or by other processes). Why?
1) the pyruvate to acetyl CoA reaction (PDH reaction) is irreversible
2) the 2Cs into the TCA cycle as acetyl CoA are balanced by the 2Cs out
as CO2; no net gain of Cs, no net gain of glucose.
Glycerol from TAG degradation is also a starting point for glucose synthesis.
Fasted state: Amino Acid Catabolism: Overview (cytoplasm and mitochondria)
Involves the removal of α-amino group by transamination and oxidative deamination.
Transamination involves transfer of α-amino group of aa to α-ketoglutarate, forming an α-keto acid plus glutamate. It is catalyzed by aminotransferases that require pyridoxal phosphate (B6 derivative). Most amino acids undergo transamination.
Glutamate undergoes oxidative deamination in the mitochondria via glutamate dehydrogenase with NAD+1 (or NADP+1), regenerating α-ketoglutarate and producing
ammonia.
The toxic ammonia is converted to non-toxic urea in the liver, or transported as non-toxic gln and ala.
The α-ketoacid derivatives are converted to intermediates of energy-producing pathways, and can be metabolized to CO2 + H2O by the TCA cycle, or used to make glucose (glucogenic) or ketones (ketogenic).
Fasted state: Urea Cycle (part in mitochondria, part in cytoplasm of hepatocytes)
Major path for disposal of nitrogen generated from the transamination and deamination of amino acids.
Urea is produced only in liver, transported to and excreted by kidney.
Requires equivalent of 4 ATP/1 urea produced.
Linked to TCA cycle by fumarate, a common intermediate.
First reaction (formation of carbamoyl phosphate by CPSI) is rate-limiting and has absolute requirement for N-acetyl glutamate.
Ornithine is used and regenerated.
Ammonia and asp are sources of urea’s N’s, CO2 (as HCO-3) the source of the C and O.
Fasted state: Branched-chain amino acids: metabolized primarily by muscle; key source of the ala used in liver
for gluconeogenesis
Transamination by branched chain aminotransferase (muscle enzyme)
Oxidative decarboxylation and formation of acyl CoA by branched-chain dehydrogenase; deficient in MSUD.
CoA derivatives are oxidized generating NADH, FADH2, acetyl CoA (leu, ile) and succinyl CoA (ile, val).
Ala and gln are released. Both transport NH3 to liver.
Ala is formed by transamination of pyruvate, sent to liver and used in gluconeogenesis. The glu from transamination can be deaminated, generating NH3.
Gln is formed by the amination of glu produced in transamination reactions. Gln metabolized by liver, kidney, gut
Fasted state: Lipolysis: FA Degradation or β-oxidation (mitochondrial matrix)
In response to a drop in insulin and/or a rise in counter-regulatory hormones (e.g.,epinephrine), TAG stored in adipose tissue are degraded to glycerol and free fatty acids by a process known as lipolysis that involves hormone-sensitive lipase (HSL; active
when phosphorylated by PKA). The fatty acids move from the adipocyte to target tissues (liver, muscle) via albumin.
In liver and muscle, LCFA are activated to their CoA derivatives by fatty acyl CoA synthetases and transported into mitochondrial matrix via the carnitine shuttle. CAT-I is
rate-limiting and regulated ( malonyl CoA). In mitochondrial matrix, FA are broken down 2 C’s at a time from COOH end to produce acetyl CoA. This process of β-oxidation requires FAD, NAD+; produces FADH2, NADH.
β-oxidation is a repetitive, 4 step sequence: dehydrogenation, hydration, dehydrogenation, thiolysis
Odd-numbered fa generate propionyl CoA in the final round. [NOTE: the propionyl CoA can be converted to succinyl CoA. This is the only example of a glucogenic precursor being produced in fa β-oxidation.]
The acetyl CoA can be used in the TCA cycle and for ketogenesis in the liver. The NADH & FADH2 generated are used in making ATP by oxidative
phosphorylation. ATP and NADH are used in gluconeogenesis. ↑ NADH ↓ TCA; the accumulating acetyl CoA inhibits PDH and activates
hepatic PC. This pushes pyruvate to gluconeogenesis. NADH, though a product, does not inhibit β-oxidation. NADH also favors OAA → malate, so acetyl CoA is pushed to KB synthesis.
Important defect in mitochondrial β oxidation is MCAD deficiency, a defect in fasting adaptation; see hypoketosis and hypoglycemia.
The most important regulator of fatty acid β-oxidation is the presence or absence of malonyl CoA. When present (during fatty acid synthesis), it inhibits CAT-1 and so
inhibits oxidation. When absent, it allows oxidation. Malonyl CoA is absent when acetyl CoA carboxylase has been inhibited (phosphorylated) by AMPK in response to ↓ATP/AMP.
Auxiliary oxidation mechanisms (impaired in Zellweger disease since can’t import peroxisomal matrix proteins; a peroxisomal biogenesis disorder)
a. peroxisomal β-oxidation
1) important for VLCFA catabolism
2) 1st step catalyzed by FP-oxidase so H2O2 is generated; catalase
3) impaired in X-linked ALD (defect in transporter of VLCFA).
b. peroxisomal α-oxidation
1) occurs at C#2 (α-C), not #3 (β-C); C#2 gets hydroxylated
2) shorten by 1C (C#1 released as CO2)
3) important for phytanic acid (branched chain fa) catabolism
i) impaired in Refsum disease: defective α-hydroxylase
Fasted state: Ketone Body Synthesis (Liver) and Utilization (non-Hepatic Tissues)
Made from acetyl CoA in liver mitochondria when I/G is low; include acetoacetate and β-hydroxybutyrate (acetone is a metabolic deadend). Makes CoA available for continued fatty acid β-oxidation.
Physiologically useful ketone bodies are organic acids.
The availability of NADH from β-oxidation favors OAA to malate and so pushes acetyl CoA to KB synthesis rather than the TCA cycle in liver.
Degraded to acetyl CoA in mitochondria of non-hepatic tissues due to presence of transferase in these tissues; especially important for brain, can cross blood brain barrier if concentrations are high, decreases (but does not eliminate) brain’s dependence on glucose.
Fasted state: oxidative phosphorylation
major source of ATP (from phosphorylation of ADP)
E for the phosphorylation rx comes from the oxidation at complex I of NADH produced in the matrix from the PDH reaction, the TCA cycle and fatty acid β-oxidation or shuttled into the mitochondria from the cytosol by the malate/aspartate and α-glycerol phosphate shuttles. Succinate is oxidized at complex II (SD).
The electrons are run down a series of multiprotein complexes (electron transport chain) to ultimately reduce O2 to 2H2O (so aerobic): components have increasingly + E°′.
As electrons are transported, a proton gradient is established that drives the phosphorylation of ADP to ATP via ATP synthase (F1/FO ATPase or complex V). Proton gradient is the common intermediate of the coupled processes of electron transport and
phosphorylation of ADP. Uncouplers dissipate the gradient and allow oxidation to occur without phosphorylation. Protons pumped at I, III, IV; P/O = 3 for NADH, 2 for succinate (FADH2). ADP in and ATP out via an antiport.
Controlled by the supply of O2, and Pi , and ADP
Recall that another source of ATP is substrate-level phosphorylation.
- seen in TCA (1) and glycolysis (2), so can occur in or outside mitochondria
- doesn’t require ETC, and so is unaffected by inhibitors of the chain
- doesn’t require O2
- does require 2 coupled rxs
- gives 1 ATP/molecule of substrate (get 2 or 3 from oxphos)
