Lactate Metabolism Flashcards
What is the only compound lactate can be converted to while actively exercising?
pyruvate
which enzyme is responsible for the conversion of lactate to pyruvate and vice versa?
Lactate Dehydrogenase (LDH)
Why can’t lactate to pyruvate conversion occur while muscle is active?
lack of NAD+
Which type of compounds facilitates Lactate Efflux?
Monocarboxylate Transporters (MCT)
Where are MCTs located?
Sarcolemma and T-tubule membrane (mitochondrial membrane)
Aside from lactate what else can MCTs transport? give an example
other monocarboxylates i.e. pyruvate
Along with lactate what other substances are carried across the membrane by MCTs? Why is this important?
H+ ions
helps manage pH, lowers cytosolic H+
Functional activity of MCT1,
dependent on a proton gradient, unidirectional transport across plasma membrane
Examples of monocarboxylates transported by MCT1
lactate,pyruvate,acetoacetic acid
Pyruvate Dehydrogenase
Irreversible decarboxylation of pyruvate to acetyl-CoA
Where is MCT 4 primarily found?
Skeletal Muscle
Skin
Vas Deferens
Where is lactate primarily utilized?
Heart
Liver
Brain and Kidney to a lesser extent
In which type of skeletal muscle is lactate primarily formed?
type IIb
In which type of skeletal muscle is lactate primarily utilized?
Type I
In type 1 muscle fibers, what is lactate converted to?
Pyruvate
In the heart what is lactate converted to?
Pyruvate
Shuttle system responsible for bringing NADH into mitochondira
Malate-Aspartate
This type of muscle has few mitochondria
Fast Glycolytic Muscle (type IIx)
What is the Cori cycle?
lactate (or pyruvate) formed in muscle can circulate to the liver where it can be synthesized to glucose. Glucose formed can then enter circulation and return to muscle
Mitochondrial LDH
Lactate dehydrogenase specific to mitochondria
Gluconeogenesis
Requires ATP; the synthesis of glucose from compounds that are not carbohydrates (pyruvate, lactate, glycerol, most aa’s)
Why is the amino acid pathway of gluconeogenesis unique?
Nitrogen group must first be removed
First step in gluconeogenesis from lactate
Conversion of lactate to pyruvate
Glucose synthesis from pyruvate (or lactate) can best be described as what?
The reversal of glycolysis
How many reversible reactions are there in glycolysis?
7
What are the irreversible glycolytic reactions?
Hexokinase
Phosphofructokinase
Pyruvate Kinase
Why is the PFK reaction not possible in reverse?
The first phosphate group in fructose 1,6 biphosphate must be removed from the first carbon, PFK can’t do this
Why is the Hexokinase reaction not possible in reverse?
Phosphoryl group needs to be removed from glucose 6 phosphate to form glucose, hexokinase can’t do this.
Why is it essential to form malate for gluconeogenesis to occur?
Malate can pass through the mitochondrial inner membrane
Where does gluconeogenesis occur?
Primarily in the cytosol, however pyruvate must be converted to oxaloacetate in mitochondria.
Glycolysis Specific enzymes
Hexokinase
Phosphofructo kinase
pyruvate kinase
Gluconeogenesis specific enzymes
Glucose 6 Phosphatase
Fructose 1,6 Biphosphatase
Pyruvate carboxylase
phosphoenolpyruvate carboxykinase
Pyruvate Carboxylase
Irreversible
Pyruvate +HCO3 + ATP > oxaloacetate + ADP + Pi + H+
Mitochondrial Malate Dehydrogenase
IN MITOCHONDRIA
Reversible
Oxaloacetate + NADH + H+ <> L-malate + NAD+
Cytosolic Malate Dehydrogenase
IN CYTOSOL
Irreversible
Malte + NAD+ > Oxaloacetate + NADH +H +
Phosphoenolpyruvate Carboxykinase
Reversible
Oxaloacetate + GTP <> Phosphoenolpyruvate + CO2 + GDP
What does low levels of Fructose 1,6 Biphosphate Indicate?
Low levels of glucose
Fructose 1,6 Biphosphatase
2nd Bypass
Irreversible hydrolysis of Carbon 1 phosphate
Fructose 1,6 Biphosphate + H20 > Fructose 6 phosphate + Pi
Phosphohexose Isomerase
Irreversible
Fructose 6 Phosphate > Glucose 6 Phosphate
Glucose 6 Phosphatase
3 rd bypass
dephosphorylation of G6P
G6P + H2O > Glucose + Pi
Main organs in which gluconeogenesis occurs?
Liver and Kidneys
Why can’t gluconeogenesis occur in muscle tissue?
Muscle tissue lacks Glucose 6 Phosphatase
What can lactate and pyruvate be converted to in muscle?
Glycogen
What are the potential fates of Glucose 6 phosphate?
Fructose 6 phosphate
Glycogen
6 phosphogluconate
What is liver glycogen broken down into?
Glucose 6 Phosphate
Where do branching enzymes act on glycogen chains?
every 4th glycosyl
What is glycogenesis
Synthesis of glycogen the storage form of glucose
Where does glycogenesis primarily occur?
Liver (hepatocytes)
Muscle cells
What is the fate of liver glycogen?
conversion to blood glucose distributed to other tissues
What is the fate of muscle glycogen?
broken down via glycolysis to provide ATP for muscle contraction
What is the glycogen core made of?
Glycogenin
what is the role of the glycogen core?
primer to which first glucose residue is attached
catalyst for synthesis of developing glycogen molecule
What other metabolic process shares the same first step as glycogenesis?
Glycolysis
Glycogen Synthase
Biosynthetic (requires energy)
adds additional glycosyl units to glycogen branch
With which molecule does glycogenesis officially start?
Glucose 6 Phosphate
Why can erythrocytes only form lactate?
no mitochondria
Phosphoglucomutase (glycogenesis)
Reversible
unique form of phosphoglucomutase
Glucose 6 phosphate <> Glucose 1 phosphate
UDP Glucose Pyrophosphorylase
RATE LIMITING STEP in glycogenesis
Irreversible
Glucose 1 Phosphate + UTP > UDP glucose + PPi
What happens if Inorganic Pyrophosphate is allowed to accumulate?
the reaction becomes unfavorable
Inorganic Pyrophosphatase
Responsible for managing PPi formed during production of UDP Glucose
- rapidly hydrolyzes PPi
Glycogen Synthase
Forms glycogen from UDP glucose,
ONLY FORMS CHAINS
extends chains
How is glycogenin formed?
protein synthesis
Branching Enzyme
Glycosyl (4>6) Tranferase or Amylo (1>4 to (1>6) transglycosylase
Branches glycogen chain at every 4th glucosyl
detaches segments of existing chain and transports to the interior.
What is glycogenolysis
the degradation of glycogen
Which enzyme catalyzes the breakdown of glycogen?
Glycogen Phosphorylase (phosphorylase)
Glycogen (n units) + Pi > Glycogen (n-1 units) + glucose 1 phosphate
Enzyme responsible for breaking down glycogen bonds in chains with 4 or fewer units from branch point?
Debranching Enzyme
Reactions catalyzed by debranching enzyme
- Transport of three (of 4) glucosyl units of a branch to the other end
- Removal of the final remaining unit by hydrolysis of glycosidic linkage (alpha1 >6)
Phosphoglucomutase (glycogenolysis)
Conversion of glucose 1 phosphate to glucose 6 phosphate
How many ATP equivalents are produced from the breakdown of G6P from glycogen? Why is this important?
3 - bypassing hexokinase reaction conserves ATP
What is the Pentose Phosphate Pathway
Conversion of 6 C Hexose to 5 C Pentose sugar
Glucose 6 phosphate > 6 phosphogluconate > Ribose 5 phosphate
Where is activity of the pentose phosphate pathway highest? where is it lowest?
Highest in adipose tissue
lowest in skeletal muscle
Which molecule regulates the first step of the pentose phosphate pathway?
NADPH
Enzyme inhibited by NADPH/NADP
Glucose 6 phosphate dehydrogenase
What does high levels of NADPH/NADP and NAD/NADH indicate
That biosynthetic and glycolytic reactions can occur at the same time
NADPH is involved in the biosynthesis of which molecules?
Fatty acids
Cholesterol (steroids)
Ribose 5 phosphate is involved in the synthesis of which molecules?
nucleotides (ATP, CoA, NAD, FAD, NADP, RNA, DNA)
