Integration Of META Flashcards
Protein, polysaccharide and lipids are broken down into what building blocks and the later broken down to
Amino acid, glucose, Glycerol &fatty acids
BB later broken down to acetyl group of acetyl coA I. E glucose–pyruvate– acetyl coA (common degradation products)
common degradation products) is then converted to?
Catabolism converts common degradation products via citric cycle yo NH3, water and co2
Polysaccharide under goes oxidative phosphorilation
Metabolic pathway is highly consrved
Catabolism typically involves _____ while anabolism involves_______
Oxidation and is energy yielding
Reduction and requires energy
Both simultaneously occurs
Highly regulated and may occur in different compartments
Cata and ana
Catabolism and anabolism must differ in at least one step for it to be independently regulated
During anabolism reducing power is usually provided by___
Nadph
Oxidative reaction of catabolism involves____ often as _____ which are transferred in _____ reactions from substrate to _____
Release of reducing equivalents often as hydride ions
To NAD
What are the four major organ that play a role in fuel metabolism
Liver adipose muscle and brain
Insulin
binds to specific, high-affinity receptors in the cell
membrane of
most tissues like
Liver, muscle and adipose
Glucose
transport in some tissues
, such as
,
increases in the
presence of insulin.
skeletal muscle and adipocytes
Other tissues such as,
do not require
insulin for glucose
uptake
hepatocytes, erythrocytes,
and cells of the nervous
system,
intestinal
mucosa, renal tubules, and cornea
Vessicles fuse to form an organnel called
Endosome
How dies insulin increase glucose uptake
STIMULATION OF INSULIN SECRETION is done by?
Insulin secretion by the β cells
of the islets of Langerhans of the pancreas is closely
coordinated with the release of glucagon by pancreatic α cells
the pancreas adjusts the levels of insulin and glucagon to make sure that the liver doesn’t produce more glucose than the body needs and that the glucose is being used efficiently by other cells in the body.
Insulin secretion is increased by:
Glucose
AA
Gastrointestinal hormones
What gastrointestinal hormones cause increase in insulin and they are also called
Cholecystokinin & gastric inhibitory peptide increase insulin levels in response to oral glucose
Incretins
gastric inhibitory peptide is also called
Glucose dependent insulinotropic peptide
INHIBITION OF INSULIN SECRETION
during periods of stress (for example, fever or
infection and
or deperession
Hunger
These effects are mediated by epinephrine secreted by adrenal medulla
Release of epinephrine is controlled by NS
Epinephrine has
a direct effect on energy metabolism, causing a rapid
mobilization
of
energy-yielding fuels, including glucose from the
liver (produced by
Glycogenolysis or gluconeogenesis and free fatty acids from adipose tissue
epinephrine can override the normal glucose-stimulated release of
insulin.
T or F
Thus, in emergency situations, the sympathetic nervous system
largely replaces the plasma glucose concentration as
the controlling influence over β-cell secretion.
Insulin effects on metabolism
Carbohydrates
Promotes it’s storage in liver, muscle & adipose
Effects of insulin on liver & muscle
Increase glycogen synthesis
In muscle & adipose
insulin increases glucose uptake by increasing
the
number of glucose transporters (
GLUT-4) in the cell membrane
intravenous administration of insulin thus causes an
immediate
decrease
in the concentration of blood gluc
In liver, insulin decreases the production of glucose through the
inhibition of glycogenolysis and gluconeogenesis
administration of insulin,causes a
significant
reduction in the release of fatty acids
Effects on lipid metabolism:
Increased
triacylglycerol synthesis:
the liver, insulin promotes the conversion of glucose into triacylglycerols, contributing to the storage of excess glucose as fat.
Insulin enhances the activity of lipoprotein lipase, an enzyme in adipose tissue that breaks down circulating triglycerides into free fatty acids and glycerol.
It provides the substrate glycerol 3-phosphate for the synthesis of triacylglycerols (fat molecules)
In liver, insulin promotes
the conversion
of glucose to
triacylglycerols
Insulin Effects on protein synthesis
In most tissues, insulin stimulates the entry of amino acids into cells, and
protein synthesis.
What hormones oppos the action of insulin
And are called “counter-regulatory hormones
Glucagon, along with epinephrine, cortisol
, and growth hormone
Most importantly
, glucagon acts to maintain blood glucose levels by
activation of hepatic glycogenolysis
and gluc
glucagon secretion is increased by:
Low blood glucose
AA increase
Epinephrine & nor epinephrine(sympathetic innervation of the pancreas
Amino acids:
Amino acids derived from a meal containing
protein
2.
stimulate the release of both glucagon and insulin. The
glucagon
effectively
prevents hypoglycemia that would otherwise occur as
a
result
of increased insulin secretion that occurs after a protein meal
INHIBITION OF GLUCAGON SECRETION
significantly decreased by elevated blood glucose and
by insulin.
Metabolic effects of glucagon
Effects
on carbohydrate metabolism
The intravenous
administration of
1.
glucagon leads to an immediate rise in blood glucose.
This results
from an
increase in the breakdown of liver (not muscle
) glycogen
and an increase
in
gluconeogenesis
Effects
on lipid metabolism
Glucagon activates lipolysis in adipose
. The
2.
free fatty acids released are taken up by liver and
oxidized to
acetyl
coenzyme A, which is used in ketone
body synthesis
.
Effects
on protein metabolism
Glucagon increases uptake
of amino
3.
acids by the liver, resulting in increased availability
of carbon
skeletons
for gluconeogenesis. As a consequence
, plasma levels of amino acids are
decreased.
glucagon is a hormone that helps the liver take in amino acids, which are the building blocks of proteins. When the liver takes in these amino acids, it can use them to create new glucose molecules through a process called gluconeogenesis. As a result, the levels of amino acids in the bloodstream decrease because they are being taken up by the liver for this process.
Hypoglycemia is characterized by:
central nervous system (CNS) symptoms, including confusion, aberrant behavior or coma
a simultaneous blood glucose= or less than 40 mg/dl
ptoms being resolved within minutes following the
administration
of glucose.
Hypoglycemia
is a medical emergency because
the CNS has an absolute
requirement for a continuous
supply of bloodborne
glucose to serve as
fuel for energy metabolism.
Transient hypoglycemia can cause cerebral dysfunction, whereas severe,
prolonged hypoglycemia
causes brain
It is, therefore, not surprising that the body has multiple overlapping
mechanisms to prevent or
correct hypoglycemia
.
Symptoms of hypoglycemia can be xteriszed into 2 namely
Adrenergic symptoms
Neuroglycopenic
Adrenergic
symptoms includes
anxiety, palpitation, tremor, and sweating are controlled by epinephrine release controlled by hypothalamus
What’s Neuroglycopenia & symptoms
the impaired
delivery of
glucose to the
brain—results in impairment of brain function causing headache,confusion, slurred speech, seizures, coma, and death
Neuroglycopenic
symptoms often result from a glucose level of
40 mg/dl.
____&______are most important in the acute, short term regulation of
blood glucose levels
Glucagon and epinephrine s
Glucagon stimulates
hepatic glycogenolysis and
gluconeogenesis.
Epinephrine promotes glycogenolysis and lipolysis, inhibits insulin
secretion, and inhibits the insulin-mediated uptake of glucose by
peripheral tissues
. Epinephrine is not normally essential in combating
hypoglycemia
,but it can assume a critical role when glucagon secretion
is deficient.
Cortisol and growth hormone are less important in the short-term maintenance of blood glucose concentrations
. They do,however, play a role in the long-term management of glucose
metabolism
Types of hypoglycemia
Insulin-induced hypoglycemia: explain
Postprandial hypoglycemia– most common occurs after eating due to an over shoot of insulin causing mild adrenergic symptoms
Fasting
hypoglycemia: rare , causes neuroglycopenia
symptoms due to reduction in rate of glucose production by hepatic glycogenolysis or gluconeogenesis
Or Alternately, fasting
hypoglycemia may be the
result of an increased rate
of glucose use by the peripheral tissues due to overproduction
of
insulin by rare pancreatic tumors
Alcohol is metabolized in the liver by _____.
two oxidation
reactions
Alcohol is metabolized in the liver through two oxidation reactions.
The first reaction involves the conversion of ethanol (alcohol) to acetaldehyde by an enzyme called alcohol dehydrogenase.
The second reaction involves the oxidation of acetaldehyde to acetate by an enzyme called aldehyde dehydrogenase.
________is a drug that inhibits aldehyde dehydrogenase, leading to the accumulation of acetaldehyde in the blood
Disulfiram
Disulfiram is used to deter alcohol ingestion by causing unpleasant symptoms when alcohol is consumed.
The accumulation of acetaldehyde in the blood due to disulfiram inhibition results in symptoms such as flushing (redness of the skin), tachycardia (rapid heart rate), hyperventilation (rapid breathing), and nausea.
Post Transcriptional Processing(Modifications)
Continuation only in eukaryote
The mRNA formed and released from the DNA template is known as the
primary transcript also known as heteronuclear mRNA or hnRNA
hmRNA It undergoes extensive processing to become the mature mRNA.
These modifications of hnRNA is
Endonuclease cleavage
Poly-A tailing
5’ capping
Methylation
Removal of introns
Splicing of exons (connect together).
Those processings occur mainly in the
nucleoplasm
In bacteria, mRNA is not changed
The statement “Translation of mRNA into proteins starts even before completion of transcription” is true in ______ but not in
prokaryotes not in eukaryotes
Post-transcriptional processing also applies to tRNA and rRNA as well.
____ end has Poly A tail
3’ end Poly-A Tailing
The 3’ terminus is polyadenylated in the nucleoplasm the ploy A tail may contain___to ___ nucleotide
20 to 250
Function of the tail
This tail protects mRNA from attack by 3’ exonuclease
Occur at ___ end
Capping at the 5’ end
Eukaryotic mRNAs are all ‘capped’ at the 5’ terminus by 7-methyl guanosine triphosphate, an unusual____ bridge is seen
5’ to 5’ triphosphate bridge is seen.
This is also done _____, this cap is useful in recognition of mRNA by the translating
machinery.
inside the nucleus
Methylation is done in _____
Cytoplasm
Methylations of ______ and _____ are common
N6 of adenine residue
2’-hydroxyl group of ribose
Removal of Introns
The primary transcripts are very long; they have molecular weights more than ____
10^7
Molecular weight of mature mRNA is about ____ meaning
1–2 x 10^6
The heavier introns are cleaved off
The primary transcript contains
coding regions (exons) and introns
Removal of introns occurs at
Splicing is an energy requiring process
This processing is done in nucleus
Spliceosomes is a combination of
SnRNPs associated with the newly formed premature rna (hnRNA) at the exon-intron junction forms spliceosome
SnRNPs make cuts at both ends of introns which are then removed and exon-exon ends are ligated
at ___
G-G residues
They contain ribozymes as well as protein components which serve to
stabilize the structure of
ribozymes.
spliceosomes are a compklex of
SnRNA, ribozymes and associated proteins
Examples of rybozymes
RNAase-P and peptidyl transferase
Ribozymes xteristic
They are enzymes made up of RNA
They are catalytic RNA molecules with sequence specific cleavage activity.
They also exhibit Michaelis-Menten kinetics.
the ribozymes are believed to be vestigial remnant
Nucleic acids were believed to be biological catalysts; and in course of evolution, proteins took
up this activit
Nucleic acids were believed to be biological catalysts; and in course of evolution, proteins took
up this activit
Difference between diabetes 1 & 2
Age onset
Nutritional status
Prevalence
Defect of deficiency
Response to oral hypglycemia
Treatment
Acute complications
Genetic disposition
Rapid–gradual – symptoms
Undernourished–obesity
10% -90%
Beta cells distriyed– resistance
No responsive – responsive
Insulin- exercise
Ketoacidosis-Hyperosmolar state
Frequency of ketosis- common – rare
Type 1 metabolic abnormalities is resent due to down indulin affecting what organs
Liver, muscle &adipose tissue
hallmarks of untreated type 1 diabetes mellitus are
Elevated levels of blood glucose and ketones
are the
Hyperglycemia in type 1 diabetes is caused by increased production of glucose by the liver and reduced uptake of glucose by peripheral tissues.
Ketosis in type 1 diabetes occurs due to
increased mobilization of fatty acids from adipose tissue, enhanced fatty acid oxidation in the liver, and synthesis of ketone bodies
Excess fatty acids that cannot be oxidized or converted into ketone bodies are converted to triacylglycerol in the liver.
The liver packages and secretes triacylglycerol in very-low-density lipoproteins (VLDL)
Diabetic individuals have elevated levels of chylomicrons and VLDL due to decreased degradation of lipoproteins in muscle and adipose tissue caused by low insulin levels
This condition of elevated levels of triacylglycerol in the blood is known as hypertriacylglycerolemia.
Individuals with type 1 diabetes must rely on exogenous
insulin
injected
subcutaneously to control the hyperglycemia and
ketoacidosis
.
occurring in over 90% of patient, insulin overdose causing hypoglycemia is common
Type 2 affecting 90% of diabetic people
People with type 2 has a combination of ___&___ problem
Insulinresistance and dysfunctional β cells
,
Type 2 P but do not require insulin to
sustain life, although insulin eventually will be required to control
hyperglycemia and keep HbA1c below 7% in 90% of patients
The metabolic alterations observed in type 2 diabetes are milder than type 1
because insulin secretion in
type 2 diabetes although not adequate does restrain ketogenesis and
blunts the development of DKA.
insulin resistance is characterized by uncontrolled hepatic
glucose production, and decreased glucose uptake by muscle and adipose tissue
Obesity is the most common cause of insulin
resistance; however, most people with obesity and insulin resistance do not
become diabetic. Due ____
Elevated levels of insulin
Insulin resistance alone will not lead to
type 2 diabetes rather
type 2 diabetes develops in insulin-resistant individuals
who also show impaired β-cell function
observed in the elderly,
and in individuals who are obese
physically inactive, or in the 3–5% of pregnant
women who develop gestational diabetes
CAUSES OF INSULIN RESISTANC
Insulin resistance increases with weight gain and, conversely,
diminishes with weight loss. This suggests that fat accumulation
is important in the development of insulin resistance
CAUSES OF INSULIN RESISTANC
Regulatory substances produced by adipocytes
include leptin and adiponectin, all of which may contribute to
the development of insulin resistance
In addition, the elevated levels of free fatty acids (FFA) that
occur in obesity have also been implicated in the development
of insulin resistance
METABOLIC abnormalities iN TYPE 2 DIABETES is due to
Insulin resistance
Hyperglycemia
Why is ketosis absent in type 2
Ketosis is usually minimal or absent in type 2 patients
because the
presence of insulin—even in the presence of insulin resistance
Dyslipidemia
chylomicron and VLDL levels are elevated
, resulting
in
hypertriacylglycerolemia
. Low HDL levels are also associated with type
2 diabetes.
In type 2 diabetes, the pancreas initially retains β-cell capacity resulting in insulin levels that vary from above normal to below normal
However
and fails
, with time, the β cell becomes increasingly dysfunctional
to secrete enough insulin to correct the prevailing
hyperglycemia
Thus
, the natural progression of the disease results in
a declining
ability to control hyperglycemia with endogenous secretion
of
insulin.
Deterioration of β-cell function may be accelerated by
the
toxic effects of sustained hyperglycemia and elevated FFA.
