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15 Cards in this Set

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absorptive state is 2-4 hours after a meal.

increases in plasma glucose, triacylglycerol and amino acids

β-cells in pancreas respond to glucose and amino acids by increasing secretion of ____ and decreasing secretion of ________
insulin

glucagon
Four mechanisms control metabolic flux:
1. Availability of substrates (Amount of time = )

2. Allosteric activation and inhibition of enzymes
(Amount of time =)

3. Covalent modification of enzymes (minutes to hours)
phosphorylation kinases
(either
serine
threonine,
tyrosine)
and dephosphorylation by phosphatases.

4. induction or repression of enzyme synthesis
(Amount of time =)
can be transcriptional or post-transcriptional regulation
minutes

minutes

minutes to hours

hours to days
allosteric =

involve rate-determining reactions
(biochemistry, of an enzyme)

binds a compound on an inactive site and thus changes conformation in order to become either active or inactiv
In the fed state, most of the enzymes are in the dephosphorylated form and are =.
In the fed state, most of the enzymes are in the dephosphorylated form and are =.
active

3 enzymes are an exception: They are inactive after dephosphorylatiton:
- Glycogen phosphorylase

- Fructose bisphosphate phosphatase-2

- Hormone sensitive lipase
Induction or repression of enzyme synthesis

Insulin  -------> glucokinase mRNA -------> 
glucokinase
Induction or repression of enzyme synthesis

Insulin -------> G6PD mRNA ------->  G6PD -------> 
6-phosphogluconate
Induction or repression of enzyme synthesis

Insulin PEP carboxykinase mRNA ------> 
PEP carboxykinase
liver is uniquely situated to process and distribute nutrients

liver takes up =
3ct
glucose,
lipid
most amino acids


nutrients are metabolized stored or rerouted to other tissues

liver buffers large variations in nutrient availability to the peripheral tissues
liver is usually a glucose-producing organ

in absorptive state, liver is a net consumer of _______

retains __of every 100g of glucose in portal vein
glucose

60
Hepatic metabolism is increased by these mechanisms:
1. increased _______ of glucose
- Glucokinase activity increases phosphorylation of glucose to =

- in the post-absorptive state glucokinase is inactive
due to high__ =

2. increased glycogen synthesis
- inactivation of glycogen phosphorylase
- activation of glycogen synthase

3. increased hexose monophosphate pathway activity

- stimulated by increased glucose-6-P and
decreased NADPH due to lipogenesis

- accounts for 5 to 10% of liver glucose utilization
phosphorylation

glucose-6-P

Km
Hepatic metabolism is increased by these mechanisms:

- ____ activity increases phosphorylation of glucose to glucose-6-P


- in the post-absorptive state glucokinase is _____
due to high Km
Glucokinase

inactive

- increased insulin to glucagon ratio stimulates
enzymes in glycolytic pathway like___ ___ & ___.
phospho-fructokinase
and
pyruvate kinase

- the product, acetyl CoA, is used as a building block
for fatty acids or provides energy by oxidation in the
TCA cycle
Hepatic metabolism (cont’d)

decreased gluconeogenesis

as glycolysis goes up, _____ goes down
gluconeogenesis

_____ _____ activity is low since acetyl
CoA levels are low, an essential allosteric activator
of this enzyme
pyruvate carboxylase

high insulin:glucagon ratio inactivates some
gluconeogenic enzymes and decreases synthesis
of PEPCK (rate-controlling enzyme of gluconeogenesis)
Absorbtive Metabolic State  Pathway
Absorbtive Metabolic State Pathway
Cori Cycle
Cori Cycle
Glucose-Alanine Cycle
Glucose-Alanine Cycle
Fat metabolism
increased fatty acid synthesis

primary site for de novo synthesis of fatty acids

favored by availability of substrates, acetyl CoA from glycolysis and NADPH from HMP pathway ....
also favored by activation of___________________ , converting acetyl CoA to malonyl CoA (rate-limiting)
acetyl CoA carboxylase


i
increased triacylglycerol synthesis

favored by availability of fatty acyl CoA from de novo synthesis and from chylomicrons and VLDLs

glycerol-3-P is available from glycolysis

triacylglycerols packaged in VLDLs are secreted by the liver for use by extrahepatic tissues (fat and muscle)
Amino acid metabolism

increased amino acid degradation

surplus amino acids sent to blood or deaminated and the carbon skeletons are either catabolized to pyruvate, acetyl CoA or TCA cycle intermediates or used for energy or fatty acid synthesis

___ ____ amino acids are degraded in muscle
branched-chain


increased protein synthesis

no storage for amino acids like glucose or fatty acids

increase in protein synthesis if needed for replacement from breakdown from previous post-absorptive state