Metabolism Flashcards
Are catabolic processes in metabolism predominantly oxidative or reductive
Oxidative
Where is NADP primarily produced?
Pentose phosphate pathway
What is the first line of energy in starvation
Liver glycogen
What intermediate becomes ketone bodies?
Acetyl- CoA
x
G-6-P
What do kinases do
Catalyse the phosphorylation of an enzyme by removing phosphate from ATP or other molecules
What does phosphatase do
Hydrolyse phosphates
Do kinases activate or inactivate degradative and biosynthetic pathways
Activat degradative pathways, inactivate biosynthetic pathways
Where are ketone bodies produced
Liver
Where are NEFAs metabolised
Muscle and Liver
How do desaturases work, which carbons can have double bond introduced
NADH reduces FAD which reduces haem containing cytochrome which reduces desaturase, oxidising fatty acid to double bond at C4,5,6,9
What are essential fatty acids in diet
Linolenic acid, arachidonic acid
Where does the first lipase work on at,,what is it
Pancreatic lipase @SI
Where does the 2nd lipase work on and what is it
Lipoprotein lipase @ muscle and adipose tissue ( also found in the heart)
What does lipoprotein lipase break down chylomicrons to
Fatty acids and Chylomicron remnants containing ADEK and phospholipid
What liberates TAG to Fatty acids and from where
Hormone sensitive lipase, TAG in adipose becomes NEFA
Where can fatty acids be stored as TAG
Muscle and adipose tissue
What is the process of digestion of TAG in SI
Bile salts act on TAG to emulsify them into micelles, pancreatic lipase then breaks it down into MAG and 2 FA
What happens to the FFA and monoglycerol after being liberated in SI
Small proportion of FFAs pass straight into blood stream and go to liver, rest get absorbed by intestinal cells
How do chylomicrons pass into blood stream
Chylomicrons pass indirectly into bloodstream ⇒ enter lymphatic system, reach the blood through thoracic duct
Where are lipoprotein lipases found - which organs
Heart, fat and muscle
What activates lipoprotein lipase
Apoprotein CII
How does insulin affect uptake of glucose in liver
It doesn’t, lol
a
G-1-P
What converts pyruvate in mitochondria to Acetyl CoA eventually in cytosol and what regulates them
Pyruvate Dehydrogenase , citrate lyase , Insulin
What is the intermediate between Acetyl-CoA and Fatty acids and what enzyme is involved
Malonyl CoA. Acetyl Co-A carboxylase
What are the substrates involved in fatty acid synthase complex
Malonyl-CoA and Acetyl-CoA
What energy stores are glucogenic
Lactate, glycerol, glucogenic amino acids
How does glucagon and insulin regulate lipogenesis
Activates AMP-activated protein kinase to inactivate acetyl-CoA carboxylase
Insulin- protein phosphatase activates…
What hormones stimulate Hormone sensitive lipase
Adrenaline, glucagon and growth hormone
How are fatty acids transported in plasma and cytoplasm
Binds to albumin in plasma and fatty acid binding protein in cytoplasm
How are fatty acids transported into mitochondria?
Becomes Acyl- CoA which binds to carnitine from intermembrane space. Acyl carnitine then enters through mito inner membrane into matrix via carrier and breaks down back to acyl coa and carnitine
What enaymes are involve in B oxidation
Ubiquinone, which gets reduced to oxidise FADH2 which then oxidises to form a double bond in Acyl CoA
How does B oxidation of fatty acids take place and what is the product
Oxidation, hydration, second oxidation( By NAD+), splitting, production of acetyl coa
What are the substrates involved in fatty acid synthase complex, what electron transporter involved here
Malonyl-CoA and Acetyl-CoA
NADPh
precursor of cholesterol synthesis that is control step
HMG-CoA to mevalonate by HMG CoA reductase (NADPH involved)
how do statins control reduce cholesterol synthesis and what enzyme do they work on
They work on HMG CoA reductase via AMP activated protein kinase
Where is cholesterol synthesized
Made mainly in the liver but also some other tissues
How do primary bile acids get formed and what are they
Hydroxylation and sidechain cleavage, chenodeoxycholate and cholate
How do bile salts get formed
Conjugation of primary bile acids with taurine or glycine
How do secondary bile acids get formed and where
Hydrolysis and partial reduction of bile salts by bacteria, in large intestine
How do primary bile acids get formed and what are they and where
Hydroxylation and sidechain cleavage, chenodeoxycholate and cholate, in liver
How do fibrates work
They inhibit recirculation of LDL
How does cholestyramine work
It binds bile acids in digestive tract and precents its reuptake and recirculation, increasing excretimg
How does cholestyramine work
It binds bile acids in digestive tract and precents its reuptake and recirculation, increasing excretion
What are essential amino acids
Cannot be synthesized within the body, must be supplied in the diet
Isoleucine, leucine, lysin, methionine, phenylalanine, threonine, tryptophan valine ,
semi- arginine and histidine
Where can glucogenic amino acids be broken down
In liver or kidney
Role of chief and parietal cells
Chief cells secrete enzymes like pepsinogen, parietal cells secrete gastric acid
What hormones regulate gastric ATPase
Gastrin, histamin, Ach
What ion movements follows exit of H+ from Gastric ATPase
K+ comes in, Cl- moves out as a counterion for HCO3-
What is pepsinogen activate by
H+, which forms pepsin which the catalyses production of more pepsin
What enzyme activates most of the pancreatic zymogens
Trypsin
What is trypsinogen activated by and what produces it
Enteropeptidase activates it and it autoactivates itself
What happens to leftover proteins in the small intestine
Gets degraded by resident peptidases like aminopeptidase
what ions bring aminoacids into the cell
Na+
Degradation of extracellular proteins
Formation of endolysosomes at acidic pH. degradation of proteins
- Bind to receptors and form endosome, then merges with lysosomes
How are intracellular proteins broken down
They are targeted for destruction by ubiquitin , proteasomes binds to protein and breaks it down
9
They are targeted for destruction by ubiquitin and broken down by proteasome
What does transamination do to aminoacid
Breaks it to carbon skeleton (ketoacid) and amino group in glutamate
Where does urea get produced
Urea cycle takes place in liver
What happens to urea in renal failure and liver cirrhosis
Rises and falls respectively
What happens to ammonia in liver cirrhosis
Rises as urea cycle is inhibited
What is the process of amino acid breakdown and how is this linked to release of ammonia from amino acids
Transamination - Nh3+ removed from amino acid by aminotransferase. oxoglutatarate becomes L-glutamate by addition of amino group, amino acid becomes oxo acid
L- glutamate which has the ammonia gets dehydrogenated by glutamate dehyrdogenase and NAD + to become 2-oxoglutarate again, NH4+ gets removed from glutamate
How does ammonia become urea
NH4+ reacts with co2 to become carbamoyl phosphate , which reacts with citrulline in mitcohondria to eventually become urea
How are amino groups transported to the liver
L-Glutamate reacts with pyruvate to become oxoglutarate and alanine to be transported in plasma ( amino group transferred from glutamate). Amino group then returned to oxoglutarate to form glutamate again
How are amino groups transported to the kindeys
Glutamate converted to gutamine by Glutamine synthetase, an amine of glutamate formed in tissues and kidneys
how is glutamine excreted
Liberates ammonia, doesnt become urea
what is the role of folic acid in synthesis of DNA
It gets converted to become FH2 and then FH4, which is needed to produce purines and thymine
Role of Vitamin B12 in methylation reactions
Needed to convert methyl FH4 into methionine for methylation reactions
role of sulphonamides
Inhibit bacterial synthesis of folic acid
role of sulphonamides
Inhibit bacterial synthesis of folic acid
How does methothrexate work
It is a derivative of folic acid and prevents reduction of FH2 to FH4
Difference between red and white muscle fibers
slow or fast contraction rate, myoglobin content, myosin atpase acitivtiy, creatine kinase activity, mitochondrial oxidation rate, glycolytic rate
slow vs fast, high vs low, low vs high, low vs high, high vs low, low vs high
Fuels for muscle contraction in anaerobic vs aerobic exercise
Anaerobic - muscle ATP, creatine phosphate, muscle glycogen
Aerobic - all these but also FFA from muscle and adopose tissue and plasma glucose from liver glycogen and gluconeogenesis
What are the main substrates of gluconeogenesis
From 3 carbon precursors:
- Alanine (from ingested protein)
- Pyruvate (from muscle protein)
- Lactate (from muscle glycogen)
- Glycerol (from fat)
Where is glucose metabolised vs galactose and fructose
by all cells vs mostly liver
What is the role of creatine phosphate
It tops up ATP store by phosphorylating ADP to ATP
What are the two main kinds of starch and which is more common
By amylose - unbranched chains, a(1-4) links, vs amylopectin, branched chains, a(1-4) and a(1-6),80-90% amylopectin
xx
xx
What enzymes digest starch
Salivary and pancreatic amylase a(1-4) - endo
glucoamylase from luminal side of intestinal wall a(1-4) - exo, oligosaccharides, trisaccharides and maltose
Isomaltase also from lumen a(1-6)
What enzymes digest disaccharises
glucoamylase a(1-4) exo, lumen , acts on oligosaccharides, trisaccharides and maltose
isolmatase. a(1-6), lumen, hydrolyses isomaltose
B galactosidase - B(1-4), lactose to glucose and galactose
Sucrase- a(1-2), sucrose to glucose and fructose
What transporter brings glucose into the intestine and what ion is involved and is capacity high or low
Na+ drags glucose through SGLT1 , low capacity
What channel allows glucose to leave intestinal cell, passiv or active
GLUT 2, passive due to high conc.
What glucose transporter is present in pancreas and liver and allows uptake of glucose prop to gluc conc
GLUT 2
What glucose transporters are responsive to insulin and where are they found
GLUT 4 , heart, muscle and fat
What are the two pathways including glucose and what are their substrates
G-6-P for glycolytic pathway and pentose phosphate pathwat
Where does glycogen get formed
Liver and muscle, kidney to some extent
ATP from glycolysis vs TCA cycle and oxidative phosphorylation
2 vs 30
Fate of glucose in anaerobic resp
Lactate from pyruvate
Is acetyl CoA involved in anaerobic respiration
NO, it is only made in mito
How is glycogen converted to glucose
Via G-1-P as an intermediate
What hormones stimulate conversion of glycogen to G-1-P
Glucagon, adrenalin and AMP
How does glucose get converted to lactate and where does it take place. What substrate required.
Oxidation of glucose to pyruvate produced NADH which is used for reduction of pyruvate to lactate, takes place in cyto of muscle
What is the cori cycle
Recycling of glucose from lactate=> lactate gets converted back to pyruvate -> G6P-> glucose
What enzymes are involved in phosphorylation of glucose to G6P and how do they differ ( saturation and cells they are present in)
Hexokinase and glucokinase, hexokinase is saturated much earlier, hexokinase present in all cells but glucokinase only in liver and B cells
What is the glycolytic pathway
Glucose gets converted to G6P. then F6P and F-1,6-bisP, then Glyceraldehyde-3P ( broken down to 3C), then phosphorylated to 1,3bisphopshoglycerate by NAD+. then ATP produced when converted to 3PG then when PEP is converted to pyruvate
what converts glycogen to G-1-P and what stimulates this process
Glycogen phosphorylase, stimulated by adrenaline and glucagon, inhibited by insulun
How does glucose can converted intp glycogen
G-1-P is converted to UDP glucose, which then becomes glucogen through removal of UDP by glycogen synthase
What stimulates action of glycogen phosphorylase
Glycogen phosphorylase b activated to a by activated phosphorylase kinase which is in turn activated by :
Ca2+ ( rises during muscle contraction,mediated by Ach) or
protein kinase A, activated by adrenaline
Glycogen phosphorylase also activated by AMP which rises during muscle contraction
Role of glucose 6 phosphatase and where is it present in
Converts G6P to glucose
Livers and kidneys
How do lactate and some amino acids get converted to glucose
They get converted to pyruvater, but conversion from PEP is irreversible, requires ATP to convert to oxaloacetate and then GTP to go to PEP
How does pentose phosphate pathway work
G6PD converts G6P into 6 phosphogluconate, which the gets dehydrogenated to Ribulose 5- phosphate (C5), which becomes ribose 5-P or xyulose 5-P. THese C5 undergo carbon shuttling reactions to eventually from 2 C6 and 1 C3
How does fructose and galactose get metabolised
Fructose can be phosphorylated by hexokinase, and fructokinase ( produced F-1-P which feeds in normal glycolytic pathway)
Galactose by galactokinase, and UDP glucose involved in converting it to G-1-P
Role of glutathione (GSH) in antioxidation
G6P oxidised to 6 phosphogluconate as in pentose pathway by G6PD, hydrogenation of NADP+ occurs. NADPH then used to reduce oxidised GSH so it can reduce peroxides (which are reactive) via gluthatione peroxidase
Does G6PDH deficiency affect males or females more and why
males, as it is x-linked
How does G6PDH deficiency affect erythrocytes
Results in GSH deficiency and leads to hemoglobin crosslinking and breakdown of erythrocytes
How does disulphiram work
Treats alcohol addiction by preventing conversion of acetalaldehyde to acetic acid,
How does alcohol lead to hypoglycaemia
Inhibits glucogenesis in liver due to reduced generation of NAD+ which is needed to oxidise lactate to pyruvate
x
Inhibits glucogenesis in liver due to reduced generation of NAD+ which is needed to oxidize lactate to pyruvate
How are ketone bodies formed
Acetyl CoA converted to HMG-COA which is then converted to acetoacetate which can be reduced by NAdh to 3-hydroxybutyrate, or decarboxylated to acetone
How does pyruvate get converted to acetyl coA
Pyruvate dehydrogenase complex, irreversible dehydrogenation by NAD+
What activates PDH kinase and phosphatase?
NADH, ATP, Acetyl coA ( eventual products of pyruvate oxidation) avs Ca2+, insulin
What coenzymes are involved in TCA cycle
2 NADH produced by TCA cycle(isocitrate to 2-oxoglutarate, 2-oxoglutarate to succinyl coA, malate to oxoloacetate), GTP produced when succinyl-CoA gets converted to Succinate
UQH2 produced (also used in fatty acid oxidation)
x
Ketogenic aminoacids, fatty acids
Where do fatty acids and ketogenic amino acids enter the TCA cycle
acetyl CoA
Where does ketogenesis take place in
Only in liver
what are the functions of the 5 different compleces in ETC
I and II are dehydrogenases, help to reduce ubiquinone, III oxidised reduced ubiquinone and reduces cytochrome C. IV oxidises cytochrome c, V produces ATP
What does antimycin and cyanide do to ETC
Inhibits electron transport along ETC
What does oligomycin do to H+ circuit in mitochondria
Acts on ATP synthase so H+ cannot enter
What do uncouplers do to mitochondria
They transport protons across the membrane (tend to be lipid soluble weak acids) protons bind to weak acid that gets through membrane and loses proton inside
Where is ubiquinone involved
Fatty acid oxidation, TCA cycle and ETC
Where is HMG CoA involved
Cholesterol synthesis and ketone body sethesis
What does myosin ATPase do
Converts ATP to ADP in exercise
What does adenylate kinase/ myokinase do
converts 2 ADP to AMP and ATP
How does insulin affect NEFA circulating
decreases due to lipolysis inhibition
Effects of AMPPK
Glucose uptake, glycolysis, fatty acid oxidation
Inhibits synthesis of glucose, cholesterol, glycogen, protein and fatty acid synthesis
which tissues does metabolism of fatty acids occure
liver and muscle
how do odd C fatty acids join TCA cycle
B oxidation to propionyl coa, caborxylation to succinyl coa
What inhibits fatty acid oxidation and how
Malonyl coa inhibits acyl carnititne
